Alcohol consumption and the risk of breast cancer

To examine the relation between alcohol consumption and breast cancer, the authors used data from the Centers for Disease Control's Cancer and Steroid Hormone Study, a multicenter population-based case-control study. Between August 1981 and December 1982, 3,498 US women aged 20-54 years with newly diagnosed breast cancer and 3,157 women aged 20-54 years selected at random from the same geographic areas were asked about their consumption of alcoholic beverages during the previous five years. Women who drank any alcohol had a risk of breast cancer of 1.0 (95% confidence interval 0.9-1.2) compared with nondrinkers. The risk of breast cancer did not increase appreciably with increasing alcohol consumption: Risk estimates for women consuming 8-14, 15-21, and 22 or more drinks per week were 1.1, 1.0, and 1.2, respectively. The authors also found no notable differences by type of beverage or within specific risk factor subgroups. These findings do not support the hypothesis that alcohol consumption increases the risk of breast cancer.     

Alcohol and breast cancer: A cohort study

The relation between alcohol consumption and several causes of death, including breast cancer, was examined in a population of 581, 321 women enrolled in a prospective study in 1959 and followed for 12 years. Women who drank occasionally had about the same breast cancer mortality rate as nondrinkers; those who drank one to four drinks per day had SMRs 7-26% higher; five drinks per day, 1.89; and six or more drinks per day, 1.65. The two highest-consumption groups' risks were significantly higher than those of nondrinkers after multivariate adjustment for several breast cancer risk factors. Distinctive dose-response relationships were observed for two known alcohol-related conditions: cirrhosis of the liver and cancer of the aero-digestive tract, suggesting that results for other causes are not seriously biased by misclassification of drinking habits. Death rates from all causes combined were elevated for drinkers of three or more drinks per day. Whether or not the association of elevated breast cancer death rates ultimately turns out to be causal, there is ample reason to continue to warn the public against excessive drinking.     

Alcohol consumption and breast cancer: a cross-national correlation study

The authors examined the cross-national correlation of alcohol consumption (based on food availability data) and breast cancer. Weighted correlation coefficients for alcohol and breast cancer were 0.31 for mortality and 0.65 for incidence; the corresponding unweighted coefficients were 0.50 and 0.45. Correlation coefficients for fat consumption and breast cancer ranged from 0.69-0.89. After adjustment for fat consumption in multiple regression models, the positive alcohol-breast cancer association disappeared, while the fat-breast cancer correlation remained positive and strong. These findings do not support the positive alcohol-breast cancer association that has been suggested by analytical epidemiological studies. The multivariate results, however, should be interpreted with caution due to the potential variation in the extent to which national alcohol data reflect consumption among females.     

Alcohol consumption and breast cancer risk in the Women's Health Study

The authors assessed the association between moderate alcohol consumption and breast cancer risk in the Women's Health Study (United States, 1992-2004). During an average of 10 years of follow-up, 1,484 cases of total breast cancer (1,190 invasive and 294 in situ) were documented among 38,454 women who, at baseline, were free of cancer and cardiovascular disease and provided detailed dietary information, including alcohol consumption, for the preceding 12 months. Higher alcohol consumption was associated with a modest increase in breast cancer risk; the multivariable relative risks for > or =30 g/day of alcohol vs. none were 1.32 (95% confidence interval (CI): 0.96, 1.82) for total breast cancer and 1.43 (95% CI: 1.02, 2.02) for invasive breast cancer. An increased risk was limited to estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors; the multivariable relative risks for an increment of 10 g/day of alcohol were 1.11 (95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24) for ER+PR- tumors (125 cases), and 0.99 (95% CI: 0.82, 1.20) for ER-PR- tumors (167 cases). The association also seemed strongest among those taking postmenopausal hormones currently, but the test for interaction was not significant. The findings from this prospective study suggest that moderate alcohol consumption increases breast cancer risk.     

Alcohol: the link between hormone replacement and breast cancer risk

Many women avoid or discontinue hormone replacement therapy due to the fear of breast cancer. They have read studies linking hormone use with increased breast cancer incidence. The link between alcohol use and breast cancer risk, in contrast, is at least as strong as that of hormone replacement therapy (HRT), yet little publicity has reached practicing physicians or patients. A new study by Ginsburg, suggests that women who use hormone replacement therapy experience an elevation in estradiol levels exceeding the ovulatory range (>300 pg/ml) with prolonged elevation for four hours, after consumption of a moderate amount of alcohol (2 to 4 ounces or .07 grams/kg). This provides a plausible explanation for the observation of increased breast cancer among women who drink alcohol regularly and suggests that a synergism between the two products may be possible. All of the epidemiologic data to date would suggest than an exposure threshold exists for hormone therapy or alcohol use. Existing literature was evaluated to identify studies that simultaneously measure alcohol and HRT exposure in relation to breast cancer incidence.

Two epidemiologic studies analyzed both exposures together. The adjustment for alcohol intake in HRT users by Kaufman eliminated any breast cancer risk associated with HRT (Relative Risk: 0.9, 95% Confidence Interval: 0.7–1.1). By subdividing the Iowa Women’s Health Study Cohort, Gapstur found that breast cancer risk was confined to women who used HRT and reported drinking at least 5 grams of alcohol per day. While more study is appropriate, these data are reminiscent of the link that was ultimately identified between the combination of oral contraceptives and smoking on arterial thrombosis. Alcohol and hormone exposure together may act synergistically to create increased breast cancer risk.

Given the prolonged elevation of estradiol levels in women who use hormones and consume moderate amounts of alcohol, new guidelines should be established to counsel women who choose to use HRT. They should be informed about the effect of moderate alcohol intake. More importantly, the women who choose to avoid alcohol while they use hormones can be reassured that there is little evidence to suggest that their risk of breast cancer is increased in any way.     

Alcohol and breast cancer in an area with high alcohol consumption

The association between alcohol drinking and breast cancer risk was investigated in 132 breast cancer cases and 499 controls with acute conditions unrelated to alcohol or any of the suspected risk factors for breast cancer, in an area which shows among the highest levels of alcohol consumption and prevalence of alcohol-related diseases in Europe (i.e. Pordenone Province, Northeastern part of Italy). Compared with non-drinkers, the multivariate odds ratio (OR) for ever drinkers was 1.5 (95% confidence interval, CI: 0.8-2.6). The risks for wine (the almost exclusive source of alcohol in the present investigation) were 1.2 for up to 1 drink, 1.4 for up to two drinks, 1.9 for up to 3 and 1.6 for over 3 drinks per day. Time-related factors (i.e. drinking habit duration and age at start of drinking) did not seem to be risk indicators.     

Alcohol exposure in utero and breast cancer risk later in life

Since the pioneering work of Hiatt and Bawol (1984), there hasamassed a considerable amount of evidence that moderate-to-heavyalcohol consumption increases risk of breast cancer in women(Willett et al., 1987; Longnecker, 1999). A plausible mechanismis by alcohol's effects on circulating hormone levels. Alcoholadministration has been reported to increase circulating oestradiollevels in pre-menopausal women (Reichman et al., 1993); theevidence is mixed in . . . [Full Text of this Article]FOOTNOTESREFERENCES     

Alcohol and cancer

Epidemiological data have identified chronic alcohol consumption as a significant risk factor for upper alimentary tract cancer, including cancer of the oropharynx, larynx and the oesophagus and of the liver. The increased risk attributable to alcohol consumption of cancer in the large intestine and in the breast is much smaller. However, although the risk is lower, carcinogenesis can be enhanced with relatively low daily doses of ethanol. Considering the high prevalence of these tumours, even a small increase in cancer risk is of great importance, especially in those individuals who exhibit a higher risk for other reasons. The epidemiological data on alcohol and other organ cancers is controversial and there is at present not enough evidence for a significant association. Although the exact mechanisms by which chronic alcohol ingestion stimulates carcinogenesis are not known, experimental studies in animals support the concept that ethanol is not a carcinogen but under certain experimental conditions is a cocarcinogen and/or tumour promoter. The metabolism of ethanol leads to the generation of acetaldehyde (AA) and free radicals. Evidence has accumulated that acetaldehyde is predominantly responsible for alcohol associated carcinogenesis. Acetaldehyde is carcinogenic and mutagenic, binds to DNA and proteins, destructs folate and results in secondary hyperproliferation. Acetaldehyde is produced by tissue alcohol hydrogenases, cytochrome P 4502E1 and through bacterial oxidative metabolism in the upper and lower gastrointestinal tract. Its generation or its degradation is modulated due to functional polymorphisms of the genes coding for the enzymes. Acetaldehyde can also be produced by oral and faecal bacteria. Smoking, which changes the oral bacterial flora, and poor oral hygiene also increase acetaldehyde. In addition, cigarette smoking and some alcoholic beverages such as calvados contain acetaldehyde. Other mechanisms by which alcohol stimulates carcinogenesis include the induction of cytochrome P-4502E1, which is associated with an enhanced production of free radicals and enhanced activation of various procarcinogens present in alcoholic beverages; in association with tobacco smoke and in diets, a change in the metabolism and distribution of carcinogens; alterations in cell cycle behaviour such as cell cycle duration leading to hyperproliferation; nutritional deficiencies, such as methyl-, vitamin E-, folate-, pyridoxal phosphate-, zinc- and selenium deficiencies and alterations of the immune system eventually resulting in an increased susceptibility to certain virus infections such as hepatitis B virus and hepatitis C virus. In addition, local mechanisms may be of particular importance. Such mechanisms lead to tissue injury such as cirrhosis of the liver, a major prerequisite for hepatocellular carcinoma. Also, an alcohol-mediated increase in oestradiols may be at least in part responsible for breast cancer risk. Thus, all these mechanisms functioning in concert actively modulate carcinogenesis leading to its stimulation.     

Alcohol and breast cancer risk: a case-control study from northern Italy.

From May 1982 to June 1985 a hospital-based case-control study of diet and breast cancer (214 cases and 215 controls) was conducted in Milan in northern Italy, an area where wine consumption is widespread. The study used a detailed diet questionnaire to obtain an estimation of total calories as well as major micro- and macro-nutrient intake. The data thus allowed an investigation of the role of alcohol in breast cancer risk, adjusting for other dietary factors, in particular total energy intake. We found positive associations between breast cancer risk and total caloric intake (chi 2 trend = 6.05, P = 0.014) but no effect for the other nutrients, when adjusted for total caloric intake. The relative risk of breast cancer, for women reporting more than 24.35 g/day of alcohol consumption (highest quintile), was 2.1 (95% confidence interval (CI): 1.1-3.9) when adjusted for non-dietary risk factors for breast cancer and 1.8 (95% CI: 1.0-3.3) when adjusted for non-alcohol caloric intake. The relative risks were moderately elevated (50% or less) for low levels of consumption and comparable to those recorded in most American studies. This finding provides further support for a moderate association between alcohol consumption and breast cancer risk, even when allowance is made for potentially relevant nutrients.     

Alcohol and oral cancer.

Alcohol, particularly when associated with tobacco use, has been recognized as an important risk factor for mouth cancer for almost 50 years. Together, they are associated with approximately 75% of upper aerodigestive tract cancers. However, intake of alcohol remains high in many countries. The rising incidence of oral cancer has prompted a revaluation of the role of alcohol (both alone and in partnership with other etiologic agents). In this article, the potential role of alcohol in the development of oral cancer is reviewed. In particular, the effect of alcohol on cellular structure and function is considered by reference to histologic and exfoliative cytologic studies of the oral epithelia. Alcohol may influence the proliferative cells by both intracellular (e.g., endocytosis) and intercellular (permeability) pathways. The carcinogenic exposure of the proliferating stem cells in the basal layer may be regulated through these pathways. Individual variation might help explain why oral cancer arises in some, but not in most, people who smoke and consume excess alcohol. Despite this finding, alcohol is strongly associated with the development of oral cancer and other upper aerodigestive tract cancers. Efforts to reduce this burden on the individual and society must be directed toward patient and professional education and research regarding (genetic) susceptibility.     

Alcohol and liver cancer.

Hepatocellular carcinoma is the eighth most frequent cancer in the world, accounting for approximately 500,000 deaths per year. Unlike many malignancies, hepatocellular carcinoma occurs predominantly within the context of known risk factors, with hepatic cirrhosis being the most common precursor to the development of hepatocellular carcinoma. After ethanol ingestion, the liver represents the major site of metabolism. Ethanol metabolism by alcohol dehydrogenase leads to the generation of acetaldehyde and free radicals that bind rapidly to numerous cellular targets, including components of cell signaling pathways and DNA. In addition to direct DNA damage, acetaldehyde depletes glutathione, an antioxidant involved in detoxification. Chronic ethanol abuse leads to induction of hepatocyte microsomal cytochrome P450 2E1, an enzyme that metabolizes ethanol to acetaldehyde and, in doing so, causes further free radical production and aberrant cell function. Cytochrome P450 2E1-dependent ethanol metabolism is also associated with activation of procarcinogens, changes in cell cycle, nutritional deficiencies, and altered immune system responses. The identification of oxidative stress in mediating many deleterious effects of ethanol in the liver has led to renewed interest in the use of dietary antioxidants as therapeutic agents. Included in this group are S-adenosyl-L-methionine and plant-derived flavanoids.     

Alcohol consumption and cancer risk

This review focuses on selected aspects of the relation between alcohol consumption and cancer risk. Heavy alcohol consumption (i.e., ≥4 drinks/day) is significantly associated with an increased risk of about 5-fold for oral and pharyngeal cancer and esophageal squamous cell carcinoma, 2.5-fold for laryngeal cancer, 50% for colorectal and breast cancers, and 30% for pancreatic cancer. These estimates are based on a large number of epidemiological studies and are generally consistent across strata of several covariates. The evidence suggests that at low doses of alcohol consumption (i.e., ≤1 drink/day) the risk is also increased by about 20% for oral and pharyngeal cancer and 30% for esophageal squamous cell carcinoma. Thus, for these sites there is little evidence of a threshold effect. While consumption of fewer than 3 alcoholic drinks/wk is not associated with an increased risk of breast cancer, an intake of 3 to 6 drinks/wk might already yield a (small) increase in risk. On the other hand, intakes up to 1 drink/day are not associated to the risk of laryngeal, colorectal, and pancreatic cancer. The positive association between alcohol consumption and the risk of head and neck cancers is independent from tobacco exposure.     

Alcohol drinking and bladder cancer

The relation between alcoholic beverage consumption and bladder cancer risk was investigated using data from a case-control study conducted between 1985 and 1992 in two areas of northern Italy. Cases were 727 patients with incident, histologically confirmed bladder cancer, and controls 1,067 patients admitted to the same network of hospitals for acute, non-neoplastic, nonurologic, or genital tract diseases. Compared to nondrinkers, the odds ratio (OR) was 0.79 (95% confidence interval, CI, 0.58-1.08) for drinkers, and 0.84 (95%CI, 0.58-1.22) for > or =6 drinks/day. The OR was 0.86 (95%CI, 0.60-1.23) for > or =5 wine drinks/day, 0.69 for beer, and 0.85 for spirits. No trend was observed with duration (OR =1.00 for > or =40 years). ORs were consistent across various strata of covariates including age, sex, and smoking habits. Our study, based on a population with high alcohol (mainly wine) intake, found no association between bladder cancer risk and alcohol intake, even at high levels of consumption.     

Alcohol drinking, consumption patterns and breast cancer among Danish nurses: a cohort study

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 17 647 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 Cox's 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 (CI): 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.     

Alcohol and epithelial ovarian cancer.

The relationship between alcohol consumption and the risk of epithelial ovarian cancer was analysed using data from a case-control study of 801 histologically confirmed epithelial ovarian cancers and 2114 controls in hospital for acute, non-neoplastic, gynecological, or hormone-related conditions, admitted to a network of teaching and general hospitals in the greater Milan area, northern Italy, i.e. a region with comparatively frequent alcohol consumption by women. Compared to alcohol abstainers, the multivariate relative risks (RRs) were 1.0 [95% confidence interval (CI), 0.7 to 1.4] for less than one, 1.1. (95% CI 0.9 to 1.6) for one to two, 1.2 (95% CI 1.0 to 1.5) for two to three and 1.3 (95% CI 0.9 to 1.8) for three or more drinks per day. A significant direct trend in risk with dose emerged. This finding chiefly derived from an association between ovarian cancer risk and consumption of wine (which accounts for over 90% of alcohol intake in this female population). Although no significant interaction between the effect of alcohol consumption and various women's characteristics emerged, there was a hint that the adverse influence of alcohol consumption is more marked in middle-age and less educated women. Thus, the results of this study suggest that relatively elevated alcohol intake (of the order of 40 g per day or more) may cause a modest increase of epithelial ovarian cancer risk.