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CORK Bibliography: Breast Cancer and Alcohol Use

42 citations. January 2003 to present

Prepared: March 2010

Berstad P; Ma HY; Bernstein L; Ursin G. Alcohol intake and breast cancer risk among young women. Breast Cancer Research and Treatment 108(1): 113-120, 2008. (33 refs.)

Introduction: Alcohol intake has been consistently associated with breast cancer risk, but the importance of timing of intake and the impact of beverage type are unclear. Methods: We evaluated whether early, lifetime or recent alcohol intake was associated with breast cancer risk, and whether risk varied by type of alcoholic drinks in 1,728 newly diagnosed population-based breast cancer patients and 435 control subjects aged 20-49 years. We used multivariable logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) as measures of the relative risk of breast cancer associated with intake of alcoholic drinks. Results Intake of alcoholic drinks during the recent five year period before the breast cancer diagnosis was associated with increased breast cancer risk (P-trend = 0.04). Intake of two or more alcoholic drinks per day during this five year period was associated with an 82% increase in breast cancer risk relative to never drinkers (OR = 1.82, 95% CI = 1.01-3.28). No risk increase was observed for alcohol intake at ages 15-20 years or for lifetime alcohol intake. Risk did not vary by type of alcohol consumed. Conclusions: Our results suggest that recent alcohol consumption may be associated with increased breast cancer risk in young women.

Bessaoud F; Daures JP. Patterns of alcohol (especially wine) consumption and breast cancer risk: A case-control study among a population in Southern France. Annals of Epidemiology 18(6): 467-475, 2008. (42 refs.)

PURPOSE: The association between alcohol consumption and breast cancer has been largely investigated, but few studies have investigated the effects of average intake when the pattern of drinking is taken into account. We sought to examine the association between drinking pattern of alcoholic beverages, particularly wine, and breast cancer using different statistical approaches. METHODS: Our study included 437 cases of breast cancer, newly diagnosed in the period 2002-2004, and 922 residence- and age-matched controls. RESULTS: Women who had an average consumption of less than 1.5 drinks per day had a lower risk (odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.34-0.97) when compared with nondrinkers. This protective effect was due substantially to wine consumption since the proportion of regular wine drinkers is predominant in our study population. Furthermore, women who consumed between 10 and 12 g/d of wine had a lower risk (OR = 0.5 1; 95% CI = 0.30-0.9 1) when compared with non-wine drinkers. Above 12 g per day of wine consumption, the risk of breast cancer increased, but the association was nonsignificant. CONCLUSIONS: Although no association between the pattern of total alcohol consumption and breast cancer was found, the type of alcoholic beverage seemed to play an important role in this association. Our results support the hypothesis that there is a threshold effect that risk decreased or was not modified for consumption under a certain threshold. Above that threshold, risk increased, however. The drinking pattern of each type of specific beverage, especially wine, seems important in terms of alcohol-breast cancer association. Low and regular wine consumption does not increase breast cancer risk.

Boffetta P; Hashibe M. Alcohol and cancer. (review). Lancet Oncology 7(2): 149-156, 2006. (73 refs.)

A causal association has been established between alcohol consumption and cancers of the oral cavity, pharynx, larynx, oesophagus, liver, colon, rectum, and, in women, breast; an association is suspected for cancers of the pancreas and lung. Evidence suggests that the effect of alcohol is modulated by polymorphisms in genes encoding enzymes for ethanol metabolism (eg, alcohol dehydrogenases, aldehyde dehydrogenases, and cytochrome P450 2E1), folate metabolism, and DNA repair. The mechanisms by which alcohol consumption exerts its carcinogenic effect have not been defined fully, although plausible events include: a genotoxic effect of acetaldehyde, the main metabolite of ethanol; increased oestrogen concentration, which is important for breast carcinogenesis; a role as solvent for tobacco carcinogens; production of reactive oxygen species and nitrogen species; and changes in folate metabolism. Alcohol consumption is increasing in many countries and is an important cause of cancer worldwide.

Brandenburg DL; Matthews AK; Johnson TP; Hughes TL. Breast cancer risk and screening: A comparison of lesbian and heterosexual women. Women & Health 45(4): 109-130, 2007. (51 refs.)

Objectives: Using data collected as part of the Multisite Womens Health Study, we examined the differences between lesbians and heterosexual women on objective breast cancer risk calculations using the Gail Model. Health risk behaviors and screening behaviors for breast cancer were also examined. It was hypothesized that lesbians would have higher ob jective cancer risk estimates and report more behavioral and screening risk factors for breast cancer than heterosexual women. Methods: Secondary data analyses were conducted using data from a study of women's health conducted from 1994 to 1996. Using a cross sectional design, a convenience sample of lesbian (n = 550) and heterosexual (n = 279) women was recruited from Chicago, New York City and Minneapolis-St. Paul. Data were collected using a self-administered questionnaire. Results: Estimates of 5-year and lifetime breast cancer risk were higher for lesbians compared to heterosexual women. Groups did not differ in self-perceptions of being overweight, but more lesbians reported heavier drinking and more reported abstinence from alcohol. Group differences in adherence to breast cancer screening were not significant. Conclusions: Findings suggest a small but statistically significant difference in the calculated breast cancer risk estimates of lesbian and heterosexual women, which seem to be largely accounted for by differences in reproductive risk factors.

Brekelmans CTM. Risk factors and risk reduction of breast and ovarian cancer. Current Opinion in Obstetrics & Gynecology 15(1): 63-68, 2003. (61 refs.)

Purpose of review. Breast and ovarian cancer remain a significant burden for women living in the Western world. This paper reviews the risk factors and current strategies to prevent these diseases. Recent findings. Established factors associated with the risk of breast cancer include family history, reproductive factors and lactation, as well as age at menarche and menopause. Hormone replacement therapy increases the risk, whereas oral contraceptives probably confer no increased risk. Alcohol moderately increases the risk, whereas a diet rich in folate and carotenoids might be protective. The role of other dietary factors, smoking and physical exercise remain unclear. Important risk factors for ovarian cancer are reproductive factors and possibly the long-term use of hormone replacement therapy. The risk is decreased by oral contraceptives. In carriers of a BRCA1 or BRCA2 gene mutation, prophylactic surgery can significantly reduce the risk of breast as well as ovarian cancer. Tamoxifen may be considered as a chemopreventive agent in women with a high risk of breast cancer, including carriers of a BRCA2 mutation, but is probably not effective in BRCA1 carriers. Summary. During the period of this review, the importance of several known risk factors was confirmed, whereas the effects of other factors became more clear. Chemoprevention and prophylactic surgery have emerged as preventative options that can reduce the risk of breast and ovarian cancer.

Brown LM; Gridley G; Wu AH; Falk RT; Hauptmann M; Kolonel LN et al. Low level alcohol intake, cigarette smoking and risk of breast cancer in Asian-American women. Breast Cancer Research and Treatment 120(1): 203-210, 2010. (40 refs.)

Studies have shown that breast cancer incidence rates among Asian migrants to the United States approach US incidence rates over several generations, implicating potentially modifiable exposures such as moderate alcohol use that has been linked to excess breast cancer risk in other populations. The goal of this study was to investigate the effect of alcohol intake, primarily low levels, on breast cancer risk in Asian-American women and explore whether smoking and alcohol contributed to the breast cancer incidence rates observed among Asian migrants to the United States. Study subjects in this population-based case-control study included 597 incident cases of breast cancer of Chinese, Japanese, and Filipino ethnicity living in San Francisco-Oakland, Los Angeles, and Oahu, Hawaii, and 966 population controls frequency matched on age, ethnicity, and area of residence. The fraction of smokers and drinkers was significantly higher in women born in Western compared with Eastern countries. However, breast cancer risk was not significantly associated with smoking (odds ratio (OR) = 1.2, 95% confidence interval (95% CI) = 0.9-1.6) or alcohol drinking (OR = 0.9, 95% CI = 0.7-1.1) in this population of low consumers of alcohol (median intake among drinkers in grams per day was 0.48 for cases and 0.40 for controls). These data suggest that low alcohol intake is not related to increased breast cancer risk in Asian-American women and that neither alcohol nor cigarette use contributed to the elevated risks in Asian-American women associated with migration patterns and Westernization.

Butler LM; Gold EB; Conroy SM; Crandall CJ; Greendale GA; Oestreicher N et al. Active, but not passive cigarette smoking was inversely associated with mammographic density. Cancer Causes & Control 21(2): 301-311, 2010. (65 refs.)

The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor, and active smoking would lend support for an antiestrogenic mechanism. We used multivariable linear regression to assess the associations of active smoking and secondhand smoke (SHS) exposure with mammographic density in 799 pre- and early perimenopausal women in the Study of Women's Health Across the Nation (SWAN). We observed that current active smoking was associated with 7.2% lower mammographic density, compared to never active smoking and no SHS exposure (p = 0.02). Starting to smoke before 18 years of age and having smoked a parts per thousand yen20 cigarettes/day were also associated with statistically significantly lower percent densities. Among nulliparous women having smoked a parts per thousand yen20 cigarettes/day was associated with 23.8% lower density, compared to having smoked a parts per thousand currency sign9 cigarettes/day (p < 0.001). Our findings support the hypothesis that tobacco smoke exerts an antiestrogenic effect on breast tissue, but counters the known increased risk of breast cancer with smoking prior to first full-term birth. Thus, our data suggest that the antiestrogenic but not the carcinogenic effects of smoking may be reflected by breast density.

Carney CP; Jones LE. The influence of type and severity of mental illness on receipt of screening mammography. Journal of General Internal Medicine 21(10): 1097-1104, 2006. (45 refs.)

BACKGROUND: Women with mental illness may be at risk for failure to receive recommended preventive services such as mammography. Little is known about whether the type or severity of mental illness influences receipt of preventive services. OBJECTIVES: To measure the influence of type and severity of mental illness on receipt of mammography. DESIGN: Retrospective study of administrative claims data, 1996 to 2001. SUBJECTS: Privately insured women age 40 to 64 years, with and without claims for mental illness, and who were eligible for mammography between 1996 and 2001. MEASUREMENTS: Odds ratios (OR) for receipt of screening mammography, any mammography, and follow-up mammography, adjusted for age, rural location, utilization of nonmental health services, and severity and type of the mental disorder. Severity measures were based on utilization of outpatient and inpatient mental health services and presence of comorbid substance use disorder. RESULTS: Women with any mental disorder were significantly less likely to receive mammography than controls. This was strongly influenced by severity of mental illness (any mammography: moderate severity OR 0.62; confidence interval [CI] 0.59 to 0.66: high severity OR 0.38; CI 0.33 to 0.43). Whereas severity contributed to lower receipt of mammography among women with mood and anxiety disorders, women with psychotic, alcohol, and substance abuse disorders had decreased odds for receipt of mammography regardless of severity. CONCLUSIONS: Women with mental disorders are at risk for failure to receive mammography, a recommended preventive service. Women with severe mental illness or psychotic and substance abuse disorders should be targeted to ensure delivery of mammography.

Choi JY; Abel J; Neuhaus T; Ko Y; Harth V; Hamajima N; Tajima K et al. Role of alcohol and genetic polymorphisms of CYP2E1 and ALDH2 in breast cancer development. Pharmacogenetics 13(2): 67-72, 2003. (13 refs.)

Objective: We examined the potential association between alcohol consumption and genetic polymorphisms in the alcohol metabolizing enzymes, CYP2E1 and ALDH2, in individual susceptibility to breast cancer in a Korean study population. Methods Three hundred and forty-six histologically confirmed breast cancer patients and 377 controls with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 1995-2001. The CYP2E1 RsaI polymorphism was determined by a real time PCR method, and the ALDH2 Glu(487) Lys polymorphism was determined by a PCR method with confronting two-pair primers (PCR-CTPP). Results The drinking women had a 1.4-fold risk for breast cancer (95% CI = 0.99-2.11) compared to never drinkers after adjustment for age and family history of breast cancer. No statistically significant overall differences were seen in the genotype frequencies between breast cancer cases and controls. However, the 'ever'-drinking women with the CYP2E1 c2 allele containing genotypes had a 1.9-fold risk (95% CI = 0.99-3.83) for developing breast cancer compared to non-drinkers with the CYP2E1 c1/c1 genotype (P for interaction = 0.043). Conclusion This study therefore suggests that the CYP2E1 c2 allele may influence the individual susceptibility to breast cancer in alcohol-consuming women.

Clarke CA; Purdie DM; Glaser SL. Population attributable risk of breast cancer in white women associated with immediately modifiable risk factors. BMC Cancer 6: article 170, 2006. (33 refs.)

Background: Estrogen/progestin replacement therapy (EPRT), alcohol consumption, physical activity, and breast-feeding duration differ from other factors associated with breast cancer in being immediately modifiable by the individual, thereby representing attractive targets for future breast cancer prevention efforts. To justify such efforts, it is vital to quantify the potential population-level impacts on breast cancer considering population variations in behavior prevalence, risk estimate, and baseline incidence. Methods: For each of these four factors, we calculated population attributable risk percents (PARs) using population-based survey ( 2001) and cancer registry data (1998-2002) for 41 subpopulations of white, non-Hispanic California women aged 40-79 years, and ranges of relative risk (RR) estimates from the literature. Results: Using a single RR estimate, subpopulation PARs ranged from 2.5% to 5.6% for hormone use, from 0.0% to 6.1% for recent consumption of >=2 alcoholic drinks daily, and 4.6% to 11.0% for physical inactivity. Using a range of RR estimates, PARs were 2-11% for EPRT use, 1-20% for alcohol consumption and 2-15% for physical inactivity. Subpopulation data were unavailable for breastfeeding, but PARs using published RR estimates ranged from 2% to 11% for lifetime breastfeeding >=31 months. Thus, of 13,019 breast cancers diagnosed annually in California, as many as 1,432 attributable to EPRT use, 2,604 attributable to alcohol consumption, 1,953 attributable to physical inactivity, and 1,432 attributable to never breastfeeding might be avoidable. Conclusion: The relatively feasible lifestyle changes of discontinuing EPRT use, reducing alcohol consumption, increasing physical activity, and lengthening breastfeeding duration could lower population breast cancer incidence substantially.

Croghan IT; Pruthi S; Hays JT; Cha S; Johnson RE; Kosel M et al. The role of smoking in breast cancer development: An analysis of a Mayo Clinic cohort. Breast Journal 15(5): 489-495, 2009. (22 refs.)

The purpose of this study was to assess the predictive value of smoking history on breast cancer diagnosis in a referral clinic population. We conducted a case-control study using clinical data collected on 8,097 female patients (1,225 breast cancer cases and 6,872 controls) seen in the Mayo Clinic Breast Clinic between August 1, 1993 and November 31, 2003. Breast cancer patients and noncancer patients significantly differed with respect to age at time of the index visit (p < 0.001), number of pregnancies (p = 0.006), number of live births (p = 0.002), vital status at last known follow-up (p < 0.001), current menstruation (p < 0.001), age at menopause (p < 0.001), history of hysterectomy (p < 0.001), use of oral contraception (p = 0.05), duration of oral contraception use (p = 0.001), use of other exogenous hormones (p < 0.001), duration of exogenous hormone use (p = 0.05), breast pain at time of index visit (p = 0.002), smoking status (p < 0.001), and use of five or more alcoholic beverages per week (p = 0.002). After adjustment for these baseline characteristics, having a personal history of smoking was found to be predictive of breast cancer diagnosis (odds ratios [OR] = 1.25, p = 0.004). Other positive predictors for breast cancer diagnosis were: age (OR = 1.02, p < 0.001), history of hysterectomy (OR = 0.66, p < 0.001), prior use of oral contraception for more than 11 years (OR = 2.10, p < 0.001), and prior use of other exogenous hormones/estrogen (OR = 1.81, p < 0.001). In this referral practice having a personal history of smoking is predictive of breast cancer diagnosis. Further studies are needed to further explore this relationship.

Dumeaux V; Lund E; Hjartaker A. Use of oral contraceptives, alcohol, and risk for invasive breast cancer. Cancer Epidemiology, Biomarkers & Prevention 13(8): 1302-1307, 2004. (36 refs.)

The aim of our study was to examine how the use of oral contraceptives (OCs) interact with alcohol on breast cancer risk within the large prospective follow-up study, Norwegian Women and Cancer Study. Between 1991 and 1997, women aged 30 to 70 years were drawn at random from the central person register and mailed an invitation. Follow-up information was collected throughout 2001 by linkage to national registries. Only women (n = 86,948) with complete information on alcohol consumption and duration of OC use were included in the present analysis. A total of 1,130 invasive breast cancers were diagnosed during 618,638 person-years of follow-up. Consumption of greater than or equal to10.0 g/d alcohol was associated with a breast cancer relative risk (95% confidence interval) of 1.69 (1.32-2.15), consistent with a linear relationship (P for trend < 0.0001). Among alcohol consumers, an excess risk of breast cancer was observed for total duration of OC use only among women who consumed <5 g/d alcohol (P for trend = 0.0009). We observed a negative interaction between duration of OC use and alcohol consumption effects (P for interaction = 0.01). After stratification on menopausal status, the association between high alcohol intake and breast cancer was more prominent among postmenopausal women than among premenopausal women (P for heterogeneity = 0.01). No interaction between alcohol and duration of OC use were significant after stratification on menopausal status. Our findings in conjunction with biological data imply that alcohol and OCs have antagonistic effects on breast cancer risk through a common pathway. Whether the interactive effect differs according to menopausal status remains unclear and needs further investigations.

Feigelson HS; Jonas CR; Robertson AS; McCullough ML; Thun MJ; Calle EE. Alcohol, folate, methionine, and risk of incident breast cancer in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiology, Biomarkers & Prevention 12(2): 161-164,, 2003. (19 refs.)

The relationship between risk of breast cancer and alcohol consumption was studied with a focus on the protective effects of adequate folate intake. The research sample included 66,561 postmenopausal women in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Cox proportional hazards models and stratified analysis were used to examine the relationship between alcohol, dietary and total folate intake, multivitamin use, dietary methionine, and breast cancer. The following results of the study were seen: (1) a total of 1,303 incident cases of breast cancer occurred during the first 5 years of follow-up; (2) an increasing risk of breast cancer with increasing alcohol consumption; (3) in the highest category of consumption (15 or more grams of ethanol/day) a risk of breast cancer of 1.26 compared with nonusers; (4) observation of this association with higher alcohol consumption for in situ, localized, and regional disease; (5) no association between risk of breast cancer and dietary folate, total folate, multivitamin use, or methionine intake; (6) no evidence of an interaction between levels of dietary folate or total folate and alcohol; and (7) no evidence of an interaction between alcohol consumption and recent or long-term multivitamin use. It is concluded that the results support a positive association with alcohol but do not support an association with folate or methionine intake or an interaction between folate and alcohol intake on risk of breast cancer.

Freudenheim JL; Bonner M; Krishnan S; Ambrosone CB; Graham S; McCann SE et al. Diet and alcohol consumption in relation to p53 mutations in breast tumors. Carcinogenesis 25(6): 931-939, 2004. (59 refs.)

There is evidence linking alcohol consumption to p53 mutations in tumors, considerable evidence linking alcohol consumption with risk of breast cancer and some evidence that alcohol and folate consumption interact to affect risk. Further, while there is some indication that oxidation may play a role in breast cancer etiology, there has been little examination of an association of oxidative stress with p53 mutations. We examined several dietary components related to one-carbon metabolism and antioxidants to determine if these factors were related to the prevalence of p53 mutations in breast tumors. We conducted a case-control study of primary, histologically confirmed breast cancer in western New York. Controls <65 were selected from drivers license lists; those greater than or equal to65 were selected from Health Care Finance Administration lists. p53 mutations in archived tumor blocks were identified in exons 2-11 and flanking intron sequences. Usual dietary intake was assessed by interview regarding intake in the previous 2 years; alcohol consumption was queried for 2, 10 and 20 years in the past. Our data were consistent with increased likelihood of tumors with p53 mutations for premenopausal breast cancer with increased alcohol intake 10 or 20 years previous; for intake of 16 or more drinks per month in the period 20 years before the interview compared with non-drinkers, the OR was 5.25, 95% CI 1.48-18.58. For postmenopausal women, there was increased likelihood of tumors with p53 mutations among women with higher folate. Antioxidant nutrients were not differentially related to p53 mutations. These results indicate that there may be heterogeneity in breast tumors, as indicated by differences in associations for those with or without p53 mutations, and that causal pathways for these nutrients may vary for pre- and postmenopausal women. For premenopausal women, alcohol consumption in the past was associated with p53 mutations.

Furberg AS; Veierod MB; Wilsgaard T; Bernstein L; Thune I. Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk. Journal of the National Cancer Institute 96(15): 1152-1160, 2004. (48 refs.)

Background: The prevalence of metabolic syndrome (obesity, glucose intolerance, low serum high-density lipoprotein cholesterol [HDL-C], high serum triglycerides, hypertension) is high and increasing in parallel with an increasing breast cancer incidence worldwide. HDL-C represents an important aspect of the syndrome, yet its role in breast cancer is still undefined. Methods: In two population-based screening surveys during 1977-1983 and 1985-1987, serum HDL-C was assayed enzymatically among 38 823 Norwegian women aged 17-54 years at entry. Height, weight, blood pressure, serum lipids, fat and energy intake, physical activity, parity, oral contraceptive use, hormone therapy use, alcohol intake, and tobacco use were also assessed. We used Cox proportional hazards modeling to estimate the relative risk (RR) of breast cancer associated with serum HDL-C levels and to adjust for potential confounding variables. We performed stratified analyses to evaluate effect modification by body mass index (BMI) and menopausal status. All statistical tests were two-sided. Results: During a median follow-up of 17.2 years, we identified 708 cases of invasive breast cancer. In multivariable analysis, the risk of postmenopausal breast cancer was inversely related to quartile of HDL-C (P-trend = .02). Among women with HDL-C above 1.64 mmol/L (highest quartile) versus below 1.20 mmol/L (lowest quartile), the relative risk was 0.75 (95% confidence interval [CI] = 0.58 to 0.97). The HDL-C association was confined to women in the heavier subgroup (BMI greater than or equal to25 kg/m(2)), for whom the relative risk of postmenopausal breast cancer in those with HDL-C above 1.64 mmol/L versus below 1.20 mmol/L was 0.43 (95% CI = 0.28 to 0.67; P-trend < .001; P-interaction = .001). Conclusion: Low HDL-C, as part of the metabolic syndrome, is associated with increased postmenopausal ;breast cancer risk.

Gavaler JS; Deal SR; Rosenblum ER. Directions for unraveling the issue of alcohol and health disparities: Findings from the Postmenopausal Health Disparities Study. Alcohol 32(1): 69-75, 2004. (46 refs.)

The Postmenopausal Health Disparities Study (PHD Study) is a model for unraveling the underlying factors that may play a role in the health status and life expectancy disparities among racial and ethnic groups, with particular attention to effects of alcoholic beverage consumption. The study is bioepidemiologic; underlying mechanisms, rather than end points per se, are evaluated. The design is cross-sectional with historical prospective elements. Data were collected from responses to three questionnaires and examination findings from a clinic visit. There were significant differences among racial and ethnic groups in patterns of alcoholic beverage consumption and selected demographic factors, body mass index, measures of physical activity and fitness, and nutritional factors. Predictors of body mass index included both moderate drinking and hormonal factors. To address the current controversy about risks and benefits of hormone replacement therapy (HRT) we examined the predictors of control-based categories of estradiol among treated women; predictors included drinking of alcohol, hormonal variables, and being Caucasian. In addition, a substantial proportion of the variables examined differed significantly between alcohol drinkers and abstainers. The significant differences between alcohol drinkers and abstainers, and among racial and ethnic groups, demonstrate the value of studying multiple racial and ethnic groups simultaneously. The PHD Study provides a unique and productive model that can be used in other populations.

Gerber B; Muller H; Reimer T; Krause A; Friese K. Nutrition and lifestyle factors on the risk of developing breast cancer. (review). Breast Cancer Research and Treatment 79(2): 265-276, 2003. (135 refs.)

Aspects of nutrition and lifestyle may be largely responsible for the development of common cancers in Western countries, as indicated by the large differences in breast cancer rates between countries, the striking changes in these rates among migrating populations, and the rapid changes over time within countries. The better informed and increasingly health-conscious population of the present day are intensively seeking to identify and eliminate these putative carcinogenic risk factors and to exploit the preventive effects that have been attributed to certain dietary components. Nutrition and 'lifestyle' may exert its carcinogenic effects indirectly by cell stimulations (alcohol, hormone therapy in postmenopause), inhibition of DNA-repair mechanisms (lack of vitamins), effecting estrogen metabolism (phytoestrogenes), or as promotors to enhance growth of tumours (body mass index). Some 'substances' may act as a carcinogenic itself, for example, aromatic hydrocarbons in tobacco or increased polycyclic aromatic hydrocarbons in well done meat. Individual differences in the effects of nutritional factors on mammary epithelia could be caused by genetic polymorphisms. In this critical review, we focus on current data regarding the effect of nutrition and lifestyle, on the risk of developing breast cancer. A health lifestyle, consisting of 'healthy diet', physical activity, renunciation of stimulants, is recommended from childhood throughout life.

Guenel P; Cyr D; Sabroe S; Lynge E; Merletti F; Ahrens W et al. Alcohol drinking may increase risk of breast cancer in men: A European population-based case-control study. Cancer Causes and Control 15(5): 571-580, 2004. (29 refs.)

Objective: It has been estimated that alcohol drinking increases the risk of breast cancer in women by approximately 7% for each increment of 10 g alcohol per day. However, the few studies conducted on breast cancer among men have failed to detect an association with quantitative measures of alcohol drinking, even if the alcohol intake is generally higher in men than in women. On the other hand, increased risks of male breast cancer were inconsistently reported in alcoholics or patients with liver cirrhosis. We have investigated the role of alcohol drinking in male breast cancer using data collected in a population-based case-control study on seven rare cancers, conducted in Denmark, France, Germany, Italy, and Sweden. Methods: The cases were 74 histologically verified male breast cancer patients aged 35-70 years. The controls (n = 1432) selected from population registers, and frequency-matched to the cases by age group and geographic area. To check for consistency, a separate analysis was conducted using as controls the patients with a rare cancer other than the breast recruited simultaneously in the European study (n = 519 men). Results: Based on population controls, the risk of developing breast cancer in men increased by 16% (95% CI: 7-26%) per 10, g alcohol/day (p < 0.001). An odds ratio of 5.89 (95% CI: 2.21-15.69) was observed for alcohol intake greater than 90 g per day, as compared with light consumers (< 15 g per day). Similar associations were observed when other rare cancers patients were used as controls. Conclusion: We found that the relative risk of breast cancer in men is comparable to that in women for alcohol intakes below 60 g per day. It continues to increase at high consumption levels not usually studied in women.

Holmes MD; Willett WC. Does diet affect breast cancer risk? (review). Breast Cancer Research 6(4): 170-178, 2004. (103 refs.)

The role of specific dietary factors in breast cancer causation is not completely resolved. Results from prospective studies do not support the concept that fat intake in middle life has a major relation to breast cancer risk. However, weight gain in middle life contributes substantially to breast cancer risk. Alcohol is the best established dietary risk factor, probably by increasing endogenous estrogen levels. Hypotheses relating diet during youth to risk decades later will be difficult to test. Nevertheless, available evidence is strong that breast cancer risk can be reduced by avoiding weight gain during adult years, and by limiting alcohol consumption.

Horn-Ross PL; Canchola AJ; West DW; Stewart SL; Bernstein L; Deapen D et al. Patterns of alcohol consumption and breast cancer risk in the California Teachers Study cohort. Cancer Epidemiology, Biomarkers & Prevention 13(3): 405-411, 2004. (19 refs.)

Alcohol consumption of approximately two drinks or more per day has been associated with elevated breast cancer risk in the California Teachers Study cohort as well as in many other populations. The objective of this analysis is to examine effects of age at drinking and drinking patterns and to identify effect modifiers. Of the 103,460 at-risk cohort members, age <85, who resided in California and completed the baseline alcohol assessment, 1,742 were diagnosed with invasive breast cancer after joining the cohort and before January 2001. Incident breast cancers were identified through the California Cancer Registry and follow-up for death and confirmation of continued California residence used various sources. Multivariate Cox proportional hazards regression models were used to estimate relative risks (RRs). Elevated breast cancer risk was most evident for recent drinking [RR = 1.28, 95% confidence interval (CI): 1.06-1.54 for >20 g/day versus nondrinkers], with no clear pattern for consumption during earlier periods of life. This elevation in risk was 32% among postmenopausal women (95% CI: 1.061.63) and 21% among pre/perimenopausal women (95% CI: 0.76-1.92). Highest risks associated with heavy alcohol consumption were observed among postmenopausal women with a history of biopsy-diagnosed benign breast disease (RR = 1.97, 95% Cl: 1.39-2.79 compared to nondrinkers without benign breast disease) or who had used combination hormone replacement therapy (HRT) (RR = 2.24, 95% CI: 1.59-3.14 compared to nondrinkers who never used HRT). Recent alcohol consumption equivalent to two or more drinks per day increases the risk of invasive breast cancer, with the greatest RRs observed among heavy drinkers who are also postmenopausal and have a history of benign breast disease or who use HRT.

Kawase T; Matsuo K; Hiraki A; Suzuki T; Watanabe M; Iwata H et al. Interaction of the effects of alcohol drinking and polymorphisms in alcohol-metabolizing enzymes on the risk of female breast cancer in Japan. Journal of Epidemiology 19(5): 244-250, 2009. (35 refs.)

Background: Epidemiological studies consistently indicate that alcoholic beverages are an independent risk factor for female breast cancer. Although the mechanism underlying this effect remains unknown, the predominant hypothesis implicates mutagenesis via the ethanol metabolite acetaldehyde, whose impact on the carcinogenesis of several types of cancer has been shown in both experimental models and molecular epidemiological studies. Many of the epidemiological Studies have investigated genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) His48Arg and aldehyde dehydrogenase-2 (ALDH2) Glu504Lys, because of the strong impact these polymorphisms have on exposure to and accumulation of acetaldehyde. With regard to breast cancer, however, evidence is scarce. Methods: To clarify the impact on female breast cancer risk of the interaction of the effects of alcohol consumption and polymorphisms in the alcohol-metabolizing enzymes ADH1B and ALDH2, we conducted a case-control study of 456 newly and histologically diagnosed breast cancer cases and 912 age- and menopausal status-matched noncancer controls. Gene-gene and gene-environment interactions between individual and combined ADH1B and ALDH2 gene polymorphisms and alcohol consumption were evaluated. Results: Despite sufficient statistical power, there was no significant impact of ADH1B and ALDH2 on the risk of breast cancer. Neither was there any significant gene-environment interactions between alcohol drinking and polymorphisms in ADH1B and ALDH2. Conclusions: Our findings do not support the hypothesis that acetaldehyde is the main contributor to the careinogenesis of alcohol-induced breast cancer.

Key J; Hodgson S; Omar RZ; Jensen TK; Thompson SG; Boobis AR et al. Meta-analysis of studies of alcohol and breast cancer with consideration of the methodological issues. Cancer Causes and Control 17(6): 759-770, 2006. (38 refs.)

Objective: To give an up-to-date assessment of the association of alcohol with female breast cancer, addressing methodological issues and shortfalls in previous overviews. Methods: Meta-analysis of studies (any language) providing original data on incidence of first primary breast cancer and alcohol. Two reviewers independently extracted data. Study quality assessed by objective criteria including degree of control for confounding; funnel plots examined for publication bias; meta-regression techniques to explore heterogeneity. Risks associated with drinking versus not drinking and dose-response not constrained through the origin estimated using random effects methods. Results: Ninety-eight unique studies were included, involving 75,728 and 60,653 cases in drinker versus non-drinker and dose-response analyses, respectively. Findings were robust to study design and analytic approaches in the meta-analyses. For studies judged high quality, controlled for appropriate confounders, excess risk associated with alcohol drinking was 22% (95% CI: 9-37%); each additional 10 g ethanol/day was associated with risk higher by 10% (95% CI: 5-15%). There was no evidence of publication bias. Risk did not differ significantly by beverage type or menopausal status. Estimated population attributable risks were 1.6 and 6.0% in USA and UK, respectively. Conclusions: Taking account of shortcomings in the study base and methodological concerns, we confirm the alcohol-breast cancer association. We compared our results to those of an individual patient data analysis, with similar findings. We conclude that the association between alcohol and breast cancer may be causal.

Key TJ; Allen NE; Spencer EA; Travis RC. Nutrition and breast cancer. Breast 12(6): 412-416, 2003. (47 refs.)

The major risk factors for breast cancer are hormone-related, and the only well-established diet-related risk factors for breast cancer are obesity and alcohol consumption. Obesity increases breast cancer risk in postmenopausal women by around 30%, probably by increasing serum concentrations of bioavailable oestradiol. Moderate alcohol intakes increase breast cancer risk by about 7% per alcoholic drink per day, perhaps also by increasing oestrogen levels. Populations with high fat intakes generally have high rates of breast cancer, but studies of individual women have not confirmed an association of high fat diets with breast cancer risk. Phyto-oestrogens can affect hormone metabolism, but data on phyto-oestrogen consumption and breast cancer risk are inconsistent. Nutrition might affect breast cancer risk by altering levels of growth factors such as insulin-like growth factor-I. Current dietary advice should be to avoid obesity, limit alcohol intake, and maintain a varied diet.

Knight JA; Bernstein L; Largent J; Capanu M; Begg CB; Mellemkjaer L et al. Alcohol intake and cigarette smoking and risk of a contralateral breast cancer. American Journal of Epidemiology 169(8): 962-968, 2009. (25 refs.)

Women with primary breast cancer are at increased risk of developing second primary breast cancer. Few studies have evaluated risk factors for the development of asynchronous contralateral breast cancer in women with breast cancer. In the Women's Environmental Cancer and Radiation Epidemiology Study (1985-2001), the roles of alcohol and smoking were examined in 708 women with asynchronous contralateral breast cancer (cases) compared with 1,399 women with unilateral breast cancer (controls). Cases and controls aged less than 55 years at first breast cancer diagnosis were identified from 5 population-based cancer registries in the United States and Denmark. Controls were matched to cases on birth year, diagnosis year, registry region, and race and countermatched on radiation treatment. Risk factor information was collected by telephone interview. Rate ratios and 95% confidence intervals were estimated by using conditional logistic regression. Ever regular drinking was associated with an increased risk of asynchronous contralateral breast cancer (rate ratio = 1.3, 95% confidence interval: 1.0, 1.6), and the risk increased with increasing duration (P = 0.03). Smoking was not related to asynchronous contralateral breast cancer. In this, the largest study of asynchronous contralateral breast cancer to date, alcohol is a risk factor for the disease, as it is for a first primary breast cancer.

Lew JQ; Freedman ND; Leitzmann MF; Brinton LA; Hoover RN; Hollenbeck AR et al. Alcohol and risk of breast cancer by histologic type and hormone receptor status in postmenopausal women. American Journal of Epidemiology 170(3): 308-317, 2009. (36 refs.)

Little is known about the association between alcohol and breast cancer by different tumor characteristics. The study consisted of 184,418 postmenopausal women aged 50-71 years in the National Institutes of Health-AARP Diet and Health Study (1995-2003). Alcohol use, diet, and potential risk factors for cancer were assessed with a mailed questionnaire at baseline. The relative risks and 95% confidence intervals were estimated by using Cox proportional hazards regression. Breast cancer cases and estrogen receptor and progesterone receptor status were identified through linkage to state cancer registries. During an average of 7 years of follow-up, 5,461 breast cancer cases were identified. Alcohol was significantly positively associated with total breast cancer: Even a moderate amount of alcohol (> 10 g/day) significantly increased breast cancer risk. In a comparison of > 35 g versus 0 g/day, the multivariate relative risks were 1.35 (95% confidence interval (CI): 1.17, 1.56) for total breast cancer, 1.46 (95% CI: 1.22, 1.75) for ductal tumors, and 1.52 (95% CI: 0.95, 2.44) for lobular tumors. The multivariate relative risks for estrogen receptor-positive/progesterone receptor-positive, estrogen receptor-positive/progesterone receptor-negative, and estrogen receptor-negative/progesterone receptor-negative tumors were 1.46 (95% CI: 1.12, 1.91) for > 35 g versus 0 g/day, 1.13 (95% CI: 0.73, 1.77) for > 20 g versus 0 g/day, and 1.21 (95% CI: 0.79, 1.84) for > 20 g versus 0 g/day, respectively. Moderate consumption of alcohol was associated with breast cancer, specifically hormone receptor-positive tumors.

Mattisson I; Wirfalt E; Wallstrom P; Gullberg B; Olsson H; Berglund G. High fat and alcohol intakes are risk factors of postmenopausal breast cancer: A prospective study from the Malmo diet and cancer cohort. International Journal of Cancer 110(4): 589-597, 2004. (63 refs.)

Associations between intakes of relative fat, total alcohol and alcoholic beverages and risk of breast cancer were examined in a subsample of 11,726 postmenopausal women from the MDC cohort. The MDC conducted baseline examinations from 1991 to 1996; the end of follow-up was 31 December 2001. Data were obtained by an interview-based diet history method, a structured questionnaire, anthropometric measurements and national and regional cancer registries. During 89,602 person-years of follow-up, 342 incident cases were documented. Cox regression analysis examined breast cancer risks adjusted for potential confounders. Two energy-adjustment approaches (i.e., adjusting for total energy vs. adjusting for nonalcohol energy) were used. High total alcohol intake was associated with a nonsignificantly elevated risk. High wine intake was associated with a significantly elevated breast cancer risk (relative risk = 2.12, 95% CI 1.24-3.60). There were significant trends of increased breast cancer risk across quintiles of relative fat intake. Mutual adjustment did not affect risk estimates for total alcohol or relative fat intakes. The specific energy-adjustment approach did not influence associations differentially.

McCarty KM; Santella RM; Steck SE; Cleveland RJ; Ahn J; Ambrosone CB et al. PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk. Environmental Health Perspectives 117(4): 552-558, 2009. (65 refs.)

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker. OBJECTIVE: We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSM) and the interaction with PAH-DNA adducts and cigarette smoking. METHODS: We conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH-DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 94 1), and smoking status was assessed by in-person questionnaires (n = 943 of 973). RESULTS: Odds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 (95% confidence interval (CI), 1.13-2.16] for detectable PAH-DNA adducts and 0.93 (95% CI, 0.56-1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82-1.69) for ever smokers and 1.44 (95% CI, 0.97-2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively). CONCLUSION: We found little statistical evidence that PAHs interacted with GSM, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk.

Public Domain

Morch LS; Johansen D; Thygesen LC; Tjonneland A; Lokkegaard E; Stahlberg C et al. Alcohol drinking, consumption patterns and breast cancer among Danish nurses: A cohort study. European Journal of Public Health 17(6): 624-629, 2007. (26 refs.)

Background: The aim of this study was to analyse the impact of alcohol intake and drinking pattern on the risk of breast cancer. Methods: A total of 17647 nurses were followed from 1993 until the end of 2001. At baseline participants completed a questionnaire on alcohol intake and other lifestyle-related factors. Data were analysed using Coxs proportional hazard model. Results: During follow-up 457 women were diagnosed with breast cancer. The relative risk of breast cancer was 2.30 [Confidence interval (Cl): 1.56-3.39] for alcohol intake of 22-27 drinks per week, compared to 1-3 drinks per week. Among alcohol consumers, weekly alcohol intake increased the risk of breast cancer with 2% for each additional drink consumed. Weekend consumption increased the risk with 4% for each additional drink consumed friday through sunday. Binge drinking of 4-5 drinks the latest weekday increased risk with 55%, compared with consumption of one drink. A possible threshold in risk estimates was found for consumption above 27 drinks per week. Conclusions: For alcohol consumption above the intake most frequently reported, the risk of breast cancer is increased. The risk is minor for moderate levels but increases for each additional drink consumed during the week. Weekend consumption and binge drinking imply an additional increase in breast cancer risk.

Nagata C; Mizoue T; Tanaka K; Tsuji I; Wakai K; Inoue M et al. Alcohol drinking and breast cancer risk: An evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Japanese Journal of Clinical Oncology 37(8): 568-574, 2007. (27 refs.)

Background: We reviewed epidemiological studies on alcohol drinking and breast cancer among the Japanese population. This report is one among a series of articles by our research group evaluating the existing evidence concerning the association between health-related lifestyles and cancer. Methods: Original data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. Results: Three cohort studies and eight case-control studies were identified. There were inconsistent results regarding alcohol drinking and breast cancer risk among cohort studies. A significant positive association was observed in one, but another showed nonsignificant inverse association. Out of the eight case-control studies, two studies showed a significantly increased risk among women who drink daily and who had higher intake of alcohol, respectively. Experimental studies have supported the biological plausibility of a positive association between alcohol drinking and breast cancer risk. Conclusion: We conclude that epidemiologic evidence on the association between alcohol drinking and breast cancer risk remains insufficient in terms of both the number and methodological quality of studies among the Japanese population.

Okasha M; McCarron P; Gunnell D; Smith GD. Exposures in childhood, adolescence and early adulthood and breast cancer risk: A systematic review of the literature. (review). Breast Cancer Research and Treatment 78(2): 223-276, 2003. (243 refs.)

A growing body of work indicates that exposures over the life course have important roles to play in the aetiology of breast cancer. This review synthesises the literature that has been published in the area of early life events and female breast cancer risk. The review finds some evidence, primarily from cohort studies on the relationship between birthweight and breast cancer, to suggest that in utero events are related to breast cancer risk in adulthood. Strong evidence to support a positive association between height and breast cancer exists. Postulated mechanisms for this relationship include the role of early diet in subsequent disease risk, and the influence of endogenous growth factors mediating the relationship. There is some evidence to suggest that leg length is the component of height which is generating the observed associations between height and breast cancer. There is no consistent pattern of association between relative weight in childhood or adolescence and risk of breast cancer. The evidence to suggest an association between physical activity in early life and breast cancer risk is convincing from case-control studies, but is not fully substantiated by the results of three cohort studies. There are inconsistent results regarding the association between smoking at a young age and breast cancer risk. There is little evidence for an association between passive smoking in early life and breast cancer risk. No clear association between early drinking and breast cancer risk exists. These results are discussed in relation to possible underlying mechanisms and health promotion strategies which could reduce breast cancer risk.

Petri AL; Tjonneland A; Gamborg M; Johansen D; Hoidrup S; Sorensen TIA et al. Alcohol intake, type of beverage, and risk of breast cancer in pre- and postmenopausal women. Alcoholism: Clinical and Experimental Research 28(7): 1084-1090, 2004. (30 refs.)

Background: Most studies of the relation between alcohol consumption and breast cancer have shown a modestly increased risk, although the results are still conflicting. Methods: The aim of this prospective population-based cohort study was to assess the influence of alcohol intake and type of beverage (beer, wine, or spirits) on breast cancer risk in relation to menopausal status. Among 13,074 women aged 20 to 91 years, we examined the relationship between breast cancer risk, total alcohol intake, and type of alcohol in relation to menopausal status. The women were classified as premenopausal or as postmenopausal at younger than 70 years or 70 years or more. Results: During follow-up, 76 premenopausal and 397 postmenopausal women developed breast cancer. Premenopausal women who had an intake of more than 27 drinks per week had a relative risk of breast cancer of 3.49 (95% confidence limits, 1.36-8.99) compared with light drinkers (p = 0.011), whereas there were no differences in risk in the lower-intake categories. The increased risk of breast cancer among premenopausal women was independent of the type of alcohol. Postmenopausal women older than 70 years of age who had an intake of more than six drinks per week of spirits had a relative risk of breast cancer of 2.43 (95% confidence limits, 1.41-4.20) compared with women who consumed less than one drink of spirits per week (p = 0.0014). Conclusions: Total alcohol intake of more than 27 drinks per week increases breast cancer risk in premenopausal women independently of the type of alcohol. Among postmenopausal women, an intake of spirits of more than six drinks per week increases breast cancer risk.

Pieta B; Samulak D; Opala T; Iwanowicz-Palus G; Wilczak M; Grodecka-Gazdecka S et al. Women's lifestyle and the risk of breast tumors. European Journal of Gynaecological Oncology 30(2): 186-189, 2009. (47 refs.)

The first behavioral aspect of mankind that has been commonly acknowledged as one of the main reasons for neoplasms is lifestyle. The specified lifestyle determines the exposure to the variety of carcinogens, whose crucial role in carcinogenesis is doubtless. The purpose of this study was to analyze women's lifestyle and its influence on the risk of developing breast cancer and benign tumors. The participants of the study were healthy women with no changes in mammary glands and women with diagnosed breast cancer or benign tumor. The total number of participants was 555 females aged 35-70 years. Every patient voluntarily filled in an anonymous questionnaire consisting of questions about socioeconomic conditions, number of cigarettes/daily, alcohol consumption, and physical activity. Proper education concerning a healthy lifestyle can positively contribute to a reduction in breast cancer. A high value of BMI, especially in the postmenopausal period, is a negative predictive factor increasing the risk of breast cancer. Physical activity decreases the risk of breast cancer. No such relation concerning smoking cigarettes has been proven.

Platek ME; Shields PG; Marian C; McCann SE; Bonner MR; Nie J et al. Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk. Cancer Epidemiology, Biomarkers & Prevention 18(9): 2453-2459, 2009. (47 refs.)

It has been hypothesized that effects of alcohol consumption on one-carbon metabolism may explain, in part, the association of alcohol consumption with breast cancer risk. The methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) genes express key enzymes in this pathway. We investigated the association of polymorphisms in MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) with breast cancer risk and their interaction with alcohol consumption in a case-control study-the Western New York Exposures and Breast Cancer study. Cases (n = 1,063) were women with primary, incident breast cancer and controls (n = 1,890) were frequency matched to cases on age and race. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. We found no association of MTHFR or MTR genotype with risk of breast cancer. In the original case-control study, there was a nonsignificant increased odds of breast cancer among women with higher lifetime drinking. In the current study, there was no evidence of an interaction of genotype and alcohol in premenopausal women. However, among postmenopausal women, there was an increase in breast cancer risk for women who were homozygote TT for MTHFR C677T and had high lifetime alcohol intake (>= 1,161.84 oz; OR, 1.92; 95% CI, 1.13-3.28) and for those who had a high number of drinks per drinking day (>1.91 drinks/day; OR, 1.80; 95% CI, 1.03-3.28) compared with nondrinkers who were homozygote CC. Our findings indicate that among postmenopausal women, increased breast cancer risk with alcohol consumption may be as a result of effects on one-carbon metabolism.

Purohit V; Khalsa J; Serrano J, eds. Mechanism of alcohol-associated cancers. Alcohol 35(3): 155-279 (entire issue), 2005. (article refs.)

This journal issue, the proceedings of a symposium, deals with the mechanisms of alcohol-associated cancers. Following an introduction and summary, there are 13 articles dealing with -- The epidemiology of alcohol-associated cancers; Alcohol and oral cancer; Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers; DNA adducts from acetaldehyde and the implications for alcohol-related carcinogenesis; Alcohol and liver cancer; Alcohol and pancreatic cancer; The etiology of alcohol-induced breast cancer; The role of methionine adenosyltransferase and S-adenosylmethionine in alcohol-associated liver cancer; The effects of alcohol on folate metabolism and the implications for carcinogenesis; Alcohol, iron-associated oxidative stress, and the relation to cancer; Alcohol, vitamin A, and cancer; Nicotine and gastric cancer; and An epidemiologic review of marijuana use and cancer risk.

Stevens RG; Cohen RD; Terry MB; Lasley BL; Siiteri P; Cohn BA. Alcohol consumption and serum hormone levels during pregnancy. Alcohol 36(1): 47-53, 2005. (42 refs.)

Factors that change sex hormone levels during pregnancy may have long-term health consequences for the offspring, including changes in breast cancer risk. A cross-sectional analysis of alcohol consumption and hormone levels in 339 pregnant women sampled from the Child Health and Development Study cohort was undertaken. Alcohol intake was queried from 1959 to 1966, long before any hazards of drinking during pregnancy were publicized. Third trimester serum hormone levels including estradiol and testosterone were analyzed. Among 339 pregnant women, 196 reported some alcohol consumption during pregnancy. The drinkers were divided into three groups with intake levels of 0.2-0.5, 0.6-2.0, and 2.1-12.5 ounces of ethanol per week. The second group corresponds to a median intake of similar to 2 drinks per week, and the last group corresponds to a median intake of similar to 1 drink per day, which is considered "light" to "moderate" drinking. Maternal estradiol levels were not associated with alcohol intake during pregnancy. However, serum testosterone was significantly lower, by 12.2%, in the latter two groups of drinking pregnant women, [confidence interval (CI) = -3.0 to 25.2] and 25.6% (CI = 9.2-39.5), respectively. The alcohol intakes reported are far below those shown to cause fetal alcohol syndrome, or any of the fetal alcohol effects so far studied. Light alcohol intake during pregnancy is associated with lower maternal testosterone. The health implications are uncertain, but may include an increased breast density in the daughters of drinking mothers.

Terry MB; Knight JA; Zablotska L; Wang Q; John EM; Andrulis IL et al. Alcohol metabolism, alcohol intake, and breast cancer risk: A sister-set analysis using the Breast Cancer Family Registry. Breast Cancer Research and Treatment 106(2): 281-288, 2007. (37 refs.)

Moderate alcohol intake has been consistently associated with a modest (30-50%) increase in breast cancer risk, but it remains unclear if certain individuals have higher susceptibility to the harmful effects of alcohol intake. Individuals differ in their ability to metabolize alcohol through genetic differences in alcohol dehydrogenase (ADH), the enzyme that catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a known carcinogen. Using data from the Breast Cancer Family Registry (n = 811 sister sets), we examined whether sisters with breast cancer differ with respect to alcohol consumption and alcohol metabolism (measured by polymorphisms in ADH1B and ADH1C) compared to their sisters without breast cancer. Neither alcohol drinking nor alcohol metabolizing ADH1B and ADH1C genotypes were associated with breast cancer risk. However, only 19% and 42% of sisters were discordant by ADH1B and ADH1C, respectively, and even fewer were discordant by both genotype and alcohol intake, making it difficult to detect differences if they existed.

Terry MB; Zhang FF; Kabat G; Britton JA; Teitelbaum SL; Neugut AI et al. Lifetime alcohol intake and breast cancer risk. Annals of Epidemiology 16(3): 230-240, 2006. (83 refs.)

PURPOSE: Moderate alcohol intake of one to two drinks per day has been consistently associated with a 30-50% increase in breast cancer. Despite the consistency in the overall association, several important questions remain, including whether the association between alcohol intake and breast cancer risk is affected by the timing of alcohol exposure, modified by other risk factors such as body mass index (BMI), menopausal status, and hormone replacement therapy (HRT), or more pronounced among hormone receptor positive tumors or invasive rather than in situ disease. METHODS: To address these questions, we conducted a large population-based study (1508 cases and 1556 controls) that collected detailed information on alcohol and other exposures throughout the lifecourse. RESULTS: Consumption of 15-30 grams/day (approximately one to two drinks) throughout life was associated with a modest 33% increase in risk (odds ratio [OR] = 1.33, 95% confidence interval (CI) = 1.01-1.74), but heavier consumption (>= 30 grams per day) was not. Risk did not vary with alcohol type (beer, wine, or hard liquor) or by patterns of use, such as recent use, intake prior to age 20 years, or whether use began at an early age. The association with lifetime intake was limited to women with a BMI < 25 (OR = 2.13, 95% CI = 1.29-3.54). Alcohol consumption of approximately one drink per day was associated with estrogen receptor positive tumors among women with a BMI < 25, but not among women BMI >= 25. Also, the elevated OR was observed only among women diagnosed with invasive (OR = 1.56, 95% CI = 1.11-2.18), but not in situ breast tumors. CONCLUSIONS: These data give added support that moderate alcohol consumption over the life course increases breast cancer risk, particularly among women with low BMI and those diagnosed with estrogen receptor positive tumors or with invasive rather than in situ disease. Risk is confined to moderate intake and does not vary with the timing of use, with heavier doses, or with the type of alcohol consumed.

Thomsen T; Esbensen BA; Samuelsen S; Tonnesen H; Moller AM. Brief preoperative smoking cessation counselling in relation to breast cancer surgery: A qualitative study. European Journal of Oncology Nursing 13(5): 344-349, 2009. (30 refs.)

Aim: To describe how women smokers with newly diagnosed breast cancer experienced brief preoperative smoking cessation intervention in relation to breast cancer surgery. Background: Preoperative smoking cessation intervention is relevant for short- and long-term risk reduction in newly diagnosed cancer patients. Our knowledge of how patients with malignant diagnoses experience preoperative smoking intervention is however scarce. Methods: A qualitative descriptive study that collected data through one-time individual, semi-structured interviews with 11 Danish women. Ricoeur's theory of interpretation was used for the analysis. Results: The women experienced that brief preoperative smoking intervention triggered reflection upon smoking and health. They furthermore experienced the smoking intervention as an opportune aid to escaping the social stigma of being a smoker. Quitting in the context of cancer diagnosis was difficult for some women. They relapsed to smoking as an ingrown response to emotional distress. The smoking intervention heightened the women's awareness of their addiction to smoking; however, they expressed a need for prolonged smoking cessation support. For others, the smoking intervention was supportive of cessation, and these women experienced smoking cessation as an enactment of a duty of responsibility to themselves and those nearest to them. They furthermore experienced a sense of personal achievement, improved well-being and endorsement from family and friends. Conclusion: In newly diagnosed breast cancer patients, brief preoperative smoking intervention motivated smoking cessation. However, prolonged intervention, pre- and postoperatively, may more effectively support cessation in breast cancer patients and should therefore be evaluated in this patient population.

Tjonneland A; Thomsen BL; Stripp C; Christensen J; Overvad K; Mellemkjaer L et al. Alcohol intake, drinking patterns and risk of postmenopausal breast cancer in Denmark: A prospective cohort study. Cancer Causes and Control 14(3): 277-284, 2003. (30 refs.)

Objective: The available epidemiological evidence indicates that drinking alcohol per se is associated with breast cancer. However, it has not been investigated how the breast cancer risk for a given total alcohol consumption depends on the drinking frequency. Methods: Within the prospective study on 'Diet, Cancer and Health', we examined the relationship between breast cancer, intake of total alcohol and frequency of drinking among 23,778 postmenopausal women, among whom 425 cases of breast cancer accrued during a median follow-up of 4.8 years. Results: The dose-response relationship between total alcohol intake and breast cancer showed an increase in the rate ratio of 1.10 per 10 g/day (95% CI: 1.04-1.16) with no evidence for differences by type of alcohol beverage. No interaction was found between drinking frequency and total alcohol intake in the risk of breast cancer (p = 0.40). Conclusions: The present study supports previous ones in showing a monotonic increase in the risk of breast cancer among postmenopausal women with increasing average daily intake of alcohol, and this relationship with alcohol intake did not depend on drinking frequency.

Trentham-Dietz A; Newcomb PA; Nichols HB; Hampton JM. Breast cancer risk factors and second primary malignancies among women with breast cancer. Breast Cancer Research and Treatment 105(2): 195-207, 2007. (48 refs.)

Purpuse To examine the association between breast cancer risk factors and second primary cancers (independent diagnoses occurring at least 12 months after the initial breast cancer diagnosis) among breast cancer survivors. Methods In this population-based study, cancer outcomes among breast cancer survivors first diagnosed during 1987-2000 were investigated. Invasive breast cancer cases were identified from the statewide tumor registry and interviewed regarding their pre-diagnosis risk factors, including reproductive and lifestyle characteristics, approximately 1 year after diagnosis. Data on second primary cancers (not recurrences) and deaths were obtained by linkage with tumor registry reports and death certificates through December 31, 2002. Hazard ratios (HR) were estimated using proportional hazards regression stratified by age and adjusted for stage and other factors. Results Among the 10,953 breast cancer cases, 10.8% experienced a second cancer diagnosis within an average of 7 years (including 488 breast, 132 colorectal, 113 endometrial, and 36 ovarian cancers). Risk of a second primary breast cancer increased according to low parity (P = 0.002), older age at menopause (P = 0.08), greater body mass index (P = 0.003) and adult weight gain (P = 0.02), and a family history of breast cancer-particularly among women with 2 or more first-degree affected relatives (HR = 1.8, 95% CI: 1.1-2.9). Reduced risk of colorectal cancer after breast cancer was observed in relation to older ages at menarche (P = 0.05), younger age at menopause (P = 0.04), postmenopausal hormone use (HR = 0.4, 95% CI: 0.3-0.7), normal body mass index (P = 0.07), and infrequent alcohol consumption (P = 0.01). Second endometrial cancer risk was associated with increasing body mass index (P < 0.01) and adult weight gain (P = 0.03). Risk of second ovarian cancer appeared related to recent alcohol intake and family history of breast cancer. Women who reported consuming any alcohol appeared to have a 55% reduction in ovarian cancer risk (95% CI: 0.2-1.0) compared to non-drinkers, while having 2 or more first-degree relatives with breast cancer was associated with an increased risk of ovarian cancer (HR = 4.3, 95% CI: 1.3-14.6). Conclution This study suggests that family history of breast cancer as well as potentially modifiable characteristics including body weight, alcohol intake, and postmenopausal hormone use may be associated with risk of a second cancer diagnosis among breast cancer cases.

Vachon CM; Sellers TA; Janney CA; Brandt KR; Carlson EE; Pankratz VS et al. Alcohol intake in adolescence and mammographic density. International Journal of Cancer 117(5): 837-841, 2005. (43 refs.)

Adolescent exposures may be important in the development of breast cancer later in life. We examined the association of adolescent alcohol consumption and adult mammographic density, a strong risk factor for breast cancer. Women within the Minnesota Breast Cancer Family Cohort with detailed mammogram and risk factor information (n = 1,893) formed our sample. Breast cancer cases were excluded. Adolescent alcohol consumption (before age 18) was solicited through a mailed questionnaire. Percent density (PD) was estimated using the computer-assisted thresholding program, Cumulus. Statistical analyses were performed using linear mixed effect models. Women who reported ever drinking alcohol before age 18 (n = 390; 21%) had a higher unadjusted PD than women who never drank during adolescence ((mu) over cap (unadj) = 26.5% vs. 22.2%), but this difference disappeared with adjustment for risk factors for mammographic density ((mu) over cap (adj) = 21.0% vs. 21.2%, p = 0.94). Adult PD was not associated with age at initiation, amount of alcohol consumed at one sitting or frequency of alcohol use before age 18. The lack of differences was seen across strata of menopausal status. There was suggestion of higher PD among heavy and more frequent drinkers (24.0%, 95% CI 21.1-26.8%) compared to lighter (21.3%, 95% CI 20.3-22.3%) and never drinkers (21.4%, 95% CI 20.9-21.9%) and also among regular adolescent drinkers who were daily or weekly adult drinkers (25.0%. 95% CI 23.0-27.0%) compared to less regular drinkers in these 2 time periods (23.0-23.4%). However, these associations were not statistically significant (p = 0.27 and p = 0.22, respectively). In summary, there was no evidence that adolescent alcohol use was associated with large and persistent effects on adult PD.

Wrensch M; Chew T; Farren G; Barlow J; Belli F; Clarke C; Erdmann CA; Lee M; Moghadassi M; Peskin-Mentzer R; Quesenberry CP; Souders-Mason V; Spence L; Suzuki M; Gould M. Risk factors for breast cancer in a population with high incidence rates. (review). Breast Cancer Research 5(4): R88-R102, 2003. (36 refs.)

Background: This report examines generally recognized breast cancer risk factors and years of residence in Marin County, California, an area with high breast cancer incidence and mortality rates. Methods: Eligible women who were residents of Marin County diagnosed with breast cancer in 1997 - 99 and women without breast cancer obtained through random digit dialing, frequency-matched by cases' age at diagnosis and ethnicity, participated in either full in-person or abbreviated telephone interviews. Results: In multivariate analyses, 285 cases were statistically significantly more likely than 286 controls to report being premenopausal, never to have used birth control pills, a lower highest lifetime body mass index, four or more mammograms in 1990 - 94, beginning drinking after the age of 21, on average drinking two or more drinks per day, the highest quartile of pack-years of cigarette smoking and having been raised in an organized religion. Cases and controls did not significantly differ with regard to having a first-degree relative with breast cancer, a history of benign breast biopsy, previous radiation treatment, age at menarche, parity, use of hormone replacement therapy, age of first living in Marin County, or total years lived in Marin County. Results for several factors differed for women aged under 50 years or 50 years and over. Conclusions: Despite similar distributions of several known breast cancer risk factors, case-control differences in alcohol consumption suggest that risk in this high-risk population might be modifiable. Intensive study of this or other areas of similarly high incidence might reveal other important risk factors proximate to diagnosis.