Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer

BACKGROUND: In vitro, human isoenzymes encoded by genes homozygous for the ADH1C*1 or ADH1B*2 alleles metabolize ethanol to acetaldehyde at a faster rate than those homozygous for the ADH1C*2 or ADH1B*1 allele. Because alcohol is a known risk factor for breast cancer, we evaluated the joint association of genetic variants in ADH and alcohol consumption in relation to breast cancer. METHODS: A nested case-control study of 321 cases and matched controls was conducted. Five single nucleotide polymorphisms (SNPs) in the ADH1C and ADH1B genes were genotyped. Logistic regression was used to assess odds ratios (ORs) and 95% confidence limits (CIs) for each SNP. Haplotype analysis of all 5 SNPs was also undertaken. RESULTS: Among drinkers, the median intake of total alcohol was 13 g/wk (10th-90th percentiles; 4.5-135.9) in cases and 18 g/wk (10th-90th percentiles; 4.5-104.1) in controls. Women who drank alcohol tended to be at an increased risk of developing breast cancer compared with those who did not drink (OR=1.40%, 95% CI 0.97-2.03), particularly those who were premenopausal at the time of breast cancer diagnosis (OR=2.69%, 95% CI: 1.00-7.26). Of the known functional alleles, breast cancer risk was not significantly increased among carriers of at least 1 ADH1C*1 or ADH1B*2 allele, when compared with those homozygous for the genotype at each locus. However, breast cancer risk tended to be lower among women who inherited the G allele at ADH1B IVS1+896A>G (OR=0.62, 95% CI 0.37-1.04). Overall haplotype frequencies were not significantly different between cases and controls. CONCLUSIONS: In this study low levels of alcohol are associated with a modest increase in breast cancer risk that is not altered by known functional allelic variants of the ADH1B and 1C gene. The protective association conferred by the G allele at ADH1B IVS1+896A>G needs further evaluation.     

Alcohol intake, consumption pattern and beverage type, and the risk of Type 2 diabetes.

AIMS: To examine associations between amount and frequency of alcohol consumption, and Type 2 diabetes. METHODS: A prospective study of 36 527 adults aged 40-69 at baseline. Incident cases of Type 2 diabetes were identified by questionnaire 4 years later. Sex-specific logistic regression models, adjusting for country of birth, dietary glycaemic index, energy intake and age, and in a second model body mass index (BMI) and waist-hip ratio (WHR), were used. RESULTS: Diabetes status was ascertained for 31 422 (86%) participants, and 362 cases identified. Former drinkers had higher risks than lifetime abstainers. Female drinkers had lower risk than lifetime abstainers (ORs < 10 g/day 0.54, 95% CI 0.36-0.82; 10-19.9 g/day 0.57, 0.34-0.94; > or = 20 g/day 0.46, 0.24-0.88, P trend = 0.005). There was no relationship after adjustment for body size. For men, a weak inverse association was observed after adjustment for body size (ORs relative to lifetime abstainers: < 10 g/day 1.56, 0.95-2.55; 10-19.9 g/day 1.21, 0.69-2.10; 20-29.9 g/day 0.80, 0.40-1.60; = 30 g/day 0.86, 0.50-1.58, P trend = 0.036). Wine was the only beverage for which an inverse association was observed. Compared with men who did not drink in the week before baseline, men who drank > or = 210 g over 1-3 days had an increased risk of diabetes (OR 5.21, 1.79-15.19), while the same amount over more days did not increase risk. CONCLUSIONS: Total alcohol intake was associated with reduced risk only in women. Alcohol from wine was associated with reduced risk of Type 2 diabetes. A high daily intake of alcohol, even on only 1-3 days a week, may increase the risk of diabetes in men.     

Mammographic parenchymal patterns and risk of breast cancer in postmenopausal women

A case-control study was conducted to assess whether certain "high-risk" mammographic parenchymal patterns are associated with the increased occurrence of breast cancer in postmenopausal women. Patients in the case group included 105 women with histologically confirmed breast cancer; subjects in the control group included 104 women with fibrocystic breast disease and 103 women with clinically normal breasts. All mammographic results were evaluated "blindly" by a radiologist who classified the breast parenchyma into "high-risk" and "low-risk" categories according to the criteria proposed by Wolfe. These data showed a similar proportion of allegedly "high-risk" breast parenchymal patterns among patients in all three groups. The finding that breast parenchymal patterns are not associated with an increased risk of breast cancer in women 50 years of age or older is consistent with the results of earlier studies in which the association is present only in younger, premenopausal women, and is absent in older, predominantly postmenopausal women. Consequently, it is concluded that these parenchymal patterns should not be used to select postmenopausal women for breast cancer screening programs, or to guide the evaluation of postmenopausal women with breast lumps or symptoms.     

Alcohol and cancer in male Japanese physicians

Summary The relationship between alcohol and sitespecific cancers was investigated in a follow-up study of 5,139 male Japanese physicians. Information on drinking habits was obtained by mail questionnaire in 1965, and cancer deaths over 12.7 years were analyzed with drinking habits classified into five categories; nondrinker, ex-drinker, occasional drinker, and daily drinker whose intake of alcohol was equivalent to less than 2 or 2 and morego ofsake (1go sake27 ml alcohol). Both age and smoking habits were taken into account in the calculation of death rates based on man-years at risk. Logistic regression analysis was also performed on cummulative mortality data. Upper aerodigestive cancer was strongly associated with alcohol consumption, giving some confidence in the validity of the present study. Excluding ex-drinkers, the risk of stomach cancer and liver cancer was gradually increased from nondrinkers to daily drinkers with lower intake of alcohol, but no further increase was noted for daily drinkers with larger consumption. Logistic regression did not show any significant associations between drinking habits and these two cancers, but the number of deaths from liver cancer was still small. Not paticular patterns were observed for cancers of the large bowel and lung.Abbreviations used UAT upper alimentary tract - URT upper respiratory tract Supported partly by the Chiyoda Mutual Foundation, Tokyo     

Alcohol Consumption and Breast Cancer Stage at Diagnosis

The stage at which breast cancer is diagnosed is an important determinant of prognosis. In contrast to the many investigations of the relationship between alcohol consumption and the risk of developing breast cancer, few have examined how alcohol consumption may affect the stage of this cancer at diagnosis. This article examines the relationship between alcohol intake and breast cancer stage and assesses consumption in relation to the volume of drinks consumed per week and the patterns of consumption 1 year prior to the breast cancer diagnosis. A total of 1191 women, aged 40 to 84 years, with newly diagnosed breast cancer were identified through the population-based Metropolitan Detroit Cancer Surveillance System, a participant of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Of these, 1011 (85%) were interviewed 2 to 4 months following diagnosis. The analyses for this article were limited to 920 cases with local and regional stage disease. The bivariate analysis showed that frequent drinkers were more likely than abstainers or infrequent drinkers to present with regional disease. Logistic regression showed that frequent drinkers were 1.45 times more likely than infrequent drinkers to be diagnosed with later stage breast cancer (95% CI: 1.01–2.10; p = 05). The association between alcohol consumption and disease stage may be due to the relationship between heavy consumption and other unhealthy behaviors. In addition, women who drink more frequently may have less awareness of and access to cancer screening services. Heavy exposure to alcohol may also contribute to accelerated tumor growth once breast cancer is present.     

Measures of adiposity and risk of breast cancer in older postmenopausal women

OBJECTIVES: To determine whether higher adiposity is associated with greater breast cancer risk in older postmenopausal women. DESIGN: Prospective cohort study with mean follow-up of 11.3 years. SETTING: Four U.S. clinical centers. PARTICIPANTS: Seven thousand five hundred twenty-three women (mean age 73.5) enrolled in the Study of Osteoporotic Fractures. MEASUREMENTS: Weight, height, and waist and hip circumference were measured at baseline. Body composition was determined using bioelectrical impedance. Risk factor information was obtained by interview and questionnaire. Bone mineral density was measured using dual energy x-ray absorptiometry. The outcome was incident invasive breast cancer, confirmed using medical records. RESULTS: After adjustment for multiple risk factors, including bone density, women in the uppermost quartiles of weight, weight gain since age 25, body mass index, waist circumference, and percentage of body fat had higher breast cancer rates than women in the first quartiles of each measure. For example, breast cancer rates were 49% higher for women in the uppermost quartile of weight (hazard ratio (HR)=1.49, 95% confidence interval (CI)=1.05-2.10), 64% higher for women in the top quartile of weight gain since age 25 (HR=1.64, 95% CI=1.15-2.34), and 58% higher for women in the top quartile of percentage of body fat (HR=1.58, 95% CI=1.11-2.23) than for women in the lowest quartile of each measure. The associations between adiposity measures and breast cancer rates were not altered when the analyses were limited to very elderly women (> or = 70). CONCLUSION: Higher adiposity is an independent risk factor for breast cancer in elderly women.     

Alcohol consumption and type 2 diabetes

To clarify the relationship between alcohol consumption and type 2 diabetes we conducted a meta-analysis of published epidemiological studies. Data from 13 cohorts were included in the analysis. The results of these studies are consistent with regard to moderate alcohol consumption, indicating a protective effect in the order of 30% (relative risk [RR]_meta=0.72, 95% CI=0.67–0.77). The reduced risk is seen in men as well as in women, although few studies investigated women. No protective effect of high alcohol consumption was seen and one cannot rule out that large intakes of alcohol may increase the risk of type 2 diabetes. Results from published studies suggest a U-shaped relationship between alcohol and type 2 diabetes, but this is based on rather few studies with heterogeneous design and definitions. It seems important to further investigate if, and to what extent, high alcohol consumption increases the risk of type 2 diabetes. Aspects of moderate alcohol consumption also need further investigation; these include type of drink, frequency of drinking, sex and ethnic differences.     

The impact of comorbidity on the survival of postmenopausal women with breast cancer

Purpose The aim was to assess the impact of comorbidity on survival of postmenopausal women with breast cancer diagnosis in the period 1995–1997.Methods The level of comorbidity was described by the methods suggested by Satariano and Charlson. Coxs proportional hazard models were used to explore the impact of comorbidity on all-cause mortality.Results After a median follow-up time of 52 months, an increasing level of comorbidity was associated with a higher all-cause mortality. Compared to patients without comorbid conditions, the hazard ratio of death (HR) was 1.2 (95% CI: 0.8–1.7) for Satariano index 1 and HR 2.3 (95% CI: 1.5–3.5) for Satariano index 2, and HR 1.6 and 2.1 for the Charlson comorbidity index, respectively. Independent of comorbidity, the treatment pattern had a strong impact on survival. The level of comorbidity has an influence on the 3-year survival of postmenopausal women with breast cancer.Conclusions Long-term follow-up is required to appraise these findings in relation to treatment strategies.     

Moderate Alcohol Consumption and Breast Cancer in Women: From Epidemiology to Mechanisms and Interventions

Epidemiologic studies indicate that moderate alcohol consumption increases breast cancer risk in women. Understanding the mechanistic basis of this relationship has important implications for women's health and breast cancer prevention. In this commentary, we focus on some recent epidemiologic studies linking moderate alcohol consumption to breast cancer risk and place the results of those studies within the framework of our current understanding of the temporal and mechanistic basis of human carcinogenesis. This analysis supports the hypothesis that alcohol acts as a weak cumulative breast carcinogen and may also be a tumor promoter. We discuss the implications of these mechanisms for the prevention and treatment of alcohol‐related breast cancer and present some considerations for future studies. Moderate alcohol consumption has been shown to benefit cardiovascular health and recently been associated with healthy aging. Therefore, a better understanding of how moderate alcohol consumption impacts breast cancer risk will allow women to make better informed decisions about the risks and benefits of alcohol consumption in the context of their overall health and at different stages of their life. Such mechanistic information is also important for the development of rational clinical interventions to reduce ethanol‐related breast cancer mortality.     

Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women

BACKGROUND: The role of androgens in breast cancer etiology has been unclear. Epidemiologic studies suggest that endogenous testosterone levels are positively associated with breast cancer risk in postmenopausal women. Given the increasing trend in the use of hormone therapies containing androgens, we evaluated the relation between the use of estrogen and testosterone therapies and breast cancer. METHODS: We conducted a prospective cohort study in the Nurses' Health Study from 1978 to 2002 to assess the risk of breast cancer associated with different types of postmenopausal hormone (PMH) formulations containing testosterone. During 24 years of follow-up (1 359 323 person-years), 4610 incident cases of invasive breast cancer were identified among postmenopausal women. Information on menopausal status, PMH use, and breast cancer diagnosis was updated every 2 years through questionnaires. RESULTS: Among women with a natural menopause, the risk of breast cancer was nearly 2.5-fold greater among current users of estrogen plus testosterone therapies (multivariate relative risk, 2.48; 95% confidence interval, 1.53-4.04) than among never users of PMHs. This analysis showed that risk of breast cancer associated with current use of estrogen and testosterone therapy was significantly greater compared with estrogen-only therapy (P for heterogeneity, .007) and marginally greater than estrogen and progesterone therapy (P for heterogeneity, .11). Women receiving PMHs with testosterone had a 17.2% (95% confidence interval, 6.7%-28.7%) increased risk of breast cancer per year of use. CONCLUSION: Consistent with the elevation in risk for endogenous testosterone levels, women using estrogen and testosterone therapies have a significantly increased risk of invasive breast cancer.     

Red meat intake and risk of breast cancer among premenopausal women

BACKGROUND: The association between red meat intake and breast cancer is unclear, but most studies have assessed diet in midlife or later. Although breast tumors differ clinically and biologically by hormone receptor status, few epidemiologic studies of diet have made this distinction. METHODS: Red meat intake and breast cancer risk were assessed among premenopausal women aged 26 to 46 years in the Nurses' Health Study II. Red meat intake was assessed with a food frequency questionnaire administered in 1991, 1995, and 1999, with respondents followed up through 2003. Breast cancers were self-reported and confirmed by review of pathologic reports. RESULTS: During 12 years of follow-up of 90,659 premenopausal women, we documented 1021 cases of invasive breast carcinoma. Greater red meat intake was strongly related to elevated risk of breast cancers that were estrogen and progesterone receptor positive (ER+/PR+; n = 512) but not to those that were estrogen and progesterone receptor negative (ER-/PR-; n = 167). Compared with those eating 3 or fewer servings per week of red meat, the multivariate relative risks (95% confidence intervals) for ER+/PR+ breast cancer with increasing servings of red meat intake were 1.14 (0.90-1.45) for more than 3 to 5 or fewer servings per week, 1.42 (1.06-1.90) for more than 5 per week to 1 or fewer servings per day, 1.20 (0.89-1.63) for more than 1 to 1.5 or fewer servings per day, and 1.97 (1.35-2.88) for more than 1.5 servings per day (test for trend, P = .001). The corresponding relative risks for ER-/PR- breast cancer were 1.34 (0.89-2.00), 1.21 (0.73-2.00), 0.69 (0.39-1.23), and 0.89 (0.43-1.84) (test for trend, P = .28). Higher intakes of several individual red meat items were also strongly related to elevated risk of ER+/PR+ breast cancer. CONCLUSION: Higher red meat intake may be a risk factor for ER+/PR+ breast cancer among premenopausal women.     

Alcohol Use and Breast Cancer: A Critical Review

The objective of this study was to outline the biological pathways of alcohol‐attributable breast cancer, the epidemiological risk relationship between alcohol consumption and breast cancer, and the global burden of breast cancer incidence and mortality attributable to alcohol consumption, with a focus on light drinking. First, the literature regarding the biological mechanisms of how alcohol affects the risk of breast cancer was reviewed and summarized. Second, a search of meta‐analyses that evaluated the risk relationship between alcohol consumption and breast cancer was conducted. Last, the burden of alcohol‐attributable breast cancer incidence and mortality was estimated by means of a Population‐Attributable Fraction methodology. Data on alcohol consumption were obtained from the Global Information System on Alcohol and Health, and data on cancer incidence and mortality were obtained from the GLOBOCAN database. Alcohol consumption affects breast cancer risk through the alteration in hormone levels and the associated biological pathways, the metabolism of ethanol resulting in carcinogens, and the inhibition of the one carbon metabolism pathway. The systematic review found 15 meta‐analyses on the risk relationship between alcohol consumption (also light consumption) and the risk of breast cancer. All but 2 of these analyses showed a dose–response relationship between alcohol consumption and the risk of breast cancer. An estimated 144,000 (95% confidence interval [CI]: 88,000 to 200,000) breast cancer cases and 38,000 (95% CI: 2,400 to 53,000) breast cancer deaths globally in 2012 were attributable to alcohol, with 18.8% of these cases and 17.5% of these deaths affecting women who were light alcohol consumers. All levels of evidence showed a risk relationship between alcohol consumption and the risk of breast cancer, even at low levels of consumption. Due to this strong relationship, and to the amount of alcohol consumed globally, the incidence of and mortality from alcohol‐attributable breast cancer is large.     

The effects of adjuvant chemotherapy on bone density in postmenopausal women with early breast cancer

PURPOSE: Adjuvant chemotherapy for breast cancer can have adverse effects on bone. We investigated the effects of adjuvant chemotherapy on bone mineral density in postmenopausal women with early-stage breast cancer. METHODS: We performed a chart review of all our breast center patients who had spine or hip bone density measured by dual-energy X-ray absorptiometry at our institution after treatment for stage I or II breast cancer. Patients who had other causes of metabolic bone disease were excluded. Multivariate regression analysis was used to adjust for confounding factors. Results were expressed as age-adjusted standard deviation units (Z scores). RESULTS: Of the 130 eligible women, 36 (28%) received adjuvant chemotherapy and 94 (72%) did not. Mean adjusted bone density scores in both the hip (0.65 SD units; 95% confidence interval [CI]: 0.32 to 0.98 SD units; P = 0.0002) and spine (0.60 SD units; 95% CI: 0.01 to 1.19 SD units; P = 0.05) were significantly lower in patients who had received adjuvant chemotherapy compared with those who had not. CONCLUSION: Women who were postmenopausal when they developed breast cancer and who received adjuvant chemotherapy had lower bone density than those who did not. Whether this effect is caused by adjuvant chemotherapy remains to be determined.