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The association of alcohol consumption with increased risk for breast cancer has been a consistent finding in a majority of epidemiologic studies during the past 2 decades. Herein, we summarize information on this association from human and animal investigations, with particular reference to epidemiologic data published since 1995. increased estrogen and androgen levels in women consuming alcohol appear to be important mechanisms underlying the association. Other plausible mechanisms include enhanced mammary gland susceptibility to carcinogenesis, increased mammary carcinogen dna damage, and greater metastatic potential of breast cancer cells, processes for which the magnitude likely depends on the amount of alcohol consumed. Susceptibility to the breast cancer-enhancing effect of alcohol may also be affected by other dietary factors (such as low folate intake), lifestyle habits (such as use of hormone replacement therapy), or biological characteristics (such as tumor hormone receptor status). Additional progress in understanding alcohol's enhancing effect on breast cancer will depend on a better understanding of the interactions between alcohol and other risk factors and on additional insights into the multiple biological mechanisms involved.

Low B-vitamin intake may increase risk of breast cancer through decreased DNA repair capacity. Alcohol intake increases risk for breast cancer, with evidence from prospective studies of an interaction between alcohol and folate. We explored dietary intake of folate and other B vitamins with risk of breast cancer in a cohort study of 34,387 postmenopausal women. To measure diet, we mailed a food frequency questionnaire; we estimated nutrient intakes and categorized them into four levels: <10th, 11th-30th, 31st-50th, and >50th percentiles. Through 12 years of follow-up, we identified 1,586 cases of breast cancer in the cohort at risk. We estimated relative risks (RRs) and 95% confidence intervals (CIs) through Cox regression models adjusted for age, energy, and other risk factors. Women in the lowest 10th percentile of folate intake from diet alone were at modestly increased risk of breast cancer relative to those above the 50th percentile: RR = 1.21 (95% CI = 0.91--1.61). We examined the joint association of folate intake and alcohol use on risk of breast cancer, with the reference group defined as women with high folate (>50th percentile) and no alcohol use. The RRs of breast cancer associated with low dietary folate intake were 1.08 (95% CI = 0.78--1.49) among nondrinkers, 1.33 (95% CI = 0.86--2.05) among drinkers of < or = 4 gm per day, and 1.59 (95% CI = 1.05--2.41) among drinkers of > 4 gm per day. These results suggest that the risks of postmenopausal breast cancer may be increased among women with low intakes of folate if they consume alcohol-containing beverages.

We investigated the relation of alcohol consumption to risk of non-Hodgkin's lymphoma (NHL) in a cohort of 35 156 Iowa women aged 55-69 years who participated in the Iowa Women's Health Study in 1986. Alcohol consumption at baseline was obtained using a mailed questionnaire. During the 9-year follow-up period, 143 incident cases of NHL were identified. Higher alcohol consumption was significantly associated with a decreased risk of NHL (P-trend = 0.03). Compared to non-drinkers, multivariate-adjusted relative risks (RRs) were decreased for women with intake of < or = 3.4 g day(-1) (RR = 0.78; 95% confidence interval (CI) 0.51-1.21) and > 3.4 g day(-1) (RR = 0.59; 0.36-0.97). The inverse association could not be attributed to one particular type of alcoholic beverage, although red wine (RR = 0.21 for > 2 glasses per month vs non-drinker; 0.05-0.86; P-trend = 0.02) has the most distinct effect. The apparent protective effect was universal regardless of specific NHL grade or Working Formulation subtype, but was most pronounced for nodal NHL (RR = 0.48; 0.26-0.90; P-trend = 0.01) and low-grade NHL (RR = 0.52; 0.21-1.26; P-trend = 0.05). These data suggest that moderate alcohol consumption is inversely associated with the risk of NHL in older women and the amount of alcohol consumed, rather than the type of alcoholic beverages, appears to be the main effect determinant.

The associations between alcohol and colon and rectal cancers were examined in the Iowa Women's Health Study. In January 1986, 41 837 postmenopausal women, aged 55-69, completed a questionnaire including usual alcohol intake and other information. Through December 1990, 237 incident colon and 75 rectal cancer cases occurred. Mantel-Haenszel age-adjusted relative risks (RR) and 95% confidence intervals (CI) for consumers of < 4.0 and > or = 4.0 g of alcohol per day compared to abstainers were 1.07 (0.61-1.89) and 1.27 (0.72-2.24) (P for trend = 0.46) for rectal cancer. Alcohol intake was inversely associated with distal colon cancer (RR for < 4.0 and > or = 4.0 g of alcohol per day were 0.64 and 0.69 respectively, P for trend = 0.04), which was specific to wine; however, no association was observed with proximal colon cancer (P for trend = 0.94). This is the only report of an inverse association between alcohol and colon cancer in women. Because gut physiology and alcohol metabolism differ between men and women, more research on the association between alcohol and colon cancer in women only, is warranted.

At least three case-control studies have examined the association between alcohol consumption and endometrial cancer; two studies showed inverse associations, and a third a positive association. To our knowledge, no prospective studies of this association have been reported. The association between alcohol and endometrial cancer was examined in the Iowa Women's Health Study (United States), a prospective study of postmenopausal women. Information on alcohol consumption and other variables was obtained through a mailed questionnaire in January 1986. Through December 1990, 167 incident endometrial cancer cases occurred in the at-risk cohort of 25,170 women. Multivariate-adjusted relative risks (RR) and 95 percent confidence intervals (CI) were computed using Cox proportional hazards regression controlling for age, body mass index (BMI), parity, age at menopause, and noncontraceptive estrogen use, and to determine multiplicative interactions. The RRs of endometrial cancer associated with < 4.0 and > or = 4.0 g of alcohol per day compared with abstainers were 0.7 (CI = 0.5-1.1) and 1.0 (CI = 0.7-1.6), respectively. No statistically significant association between endometrial cancer and consumption of either beer, wine, or liquor was observed. There was no interaction between alcohol and any other endometrial cancer risk factors, including BMI or noncontraceptive estrogen use. These data do not support an association between alcohol and endometrial cancer among postmenopausal women.

Chromatographic, peptide mapping and mass spectrometric analysis were used to examine hemoglobin (Hb) from heavy drinkers and abstainers for alcohol consumption-related modifications. Heavy drinker and abstainer hemoglobin samples contained similar amounts of glycosylated Hb and significantly different (p < 0.05) amounts of "fast" hemoglobin. The presence of higher amounts of "fast" Hb in heavy drinker relative to abstainer samples suggested the presence of alcohol-consumption related modifications. To further examine Hb for modifications, tryptic peptides of the "fast" hemoglobin HbA1c were isolated and analyzed by plasma desorption mass spectrometry (PDMS). [14C]acetaldehyde (AcH)-Hb was synthesized in vivo for use as a standard. Specific peptides were chosen based on co-migration with radiolabeled peptides from a tryptic digest of the [14C]acetaldehyde-Hb. The masses obtained by PDMS for two heavy drinker peptides were identical to two radiolabeled peptides; the two pairs of peptides co-migrated on HPLC. A comparison of the observed mass for the peptides with the theoretical masses for acetaldehyde-modified Hb peptides suggested that the peptides were AcH-modified alpha and beta chain N-termini of Hb. The modified peptides were found in five of six heavy drinker samples. This is the first description of site-specific AcH-Hb adducts occurring in vivo. The routine detection of such adducts has potential for characterizing usual alcohol intake.

The association between breast cancer incidence and alcohol consumption among postmenopausal women was examined in the Iowa Women's Health Study. In January 1986, a cohort of 41,837 postmenopausal women, aged 55-69 years, completed a questionnaire that included alcohol intake and other information. Through December 1989, 493 incident breast cancer cases were identified. Age-adjusted relative risks of consumption of less than 1.5, 1.5-4.9, 5.0-14.9, and 15.0 g or more of alcohol per day compared with abstention were 1.08, 1.10, 1.08, and 1.28, respectively (p for trend = 0.11). After controlling for age, body mass index, age at first livebirth, age at menarche, and family history of breast cancer, the relative risks were 1.18, 1.20, 1.25, and 1.46 (p for trend = 0.04). Multivariate modeling, using Cox proportional hazards regression, revealed a significant multiplicative interaction between alcohol intake and noncontraceptive estrogen use. The relative risks of breast cancer associated with average daily alcohol consumption of 5.0-14.9 and 15.0 g or more were 1.88 (95% confidence interval 1.30-2.72) and 1.83 (95% confidence interval 1.18-2.85), respectively, among ever-users of estrogen; no association between alcohol and breast cancer was observed among never-users of estrogen.