Alcohol consumption‐associated breast cancer incidence and potential effect modifiers: the Japan Public Health Center‐based Prospective Study

Abstract

Epidemiological studies have evaluated whether the impact of alcohol intake on breast cancer risk is modified by use of exogenous estrogens, folate intake, body weight and smoking status, but results have been inconsistent. Further, effect modification by intake of isoflavones and alcohol-induced facial flushing, which are prevalent in Asian populations, have not been investigated. We investigated the association between alcohol intake and breast cancer risk and whether the association is modified by these factors among 50,757 premenopausal and postmenopausal women (aged 40-69 years) in the population-based Japan Public Health Center-based Prospective Study. Alcohol consumption and other related factors were assessed using self-reported questionnaires. Through to the end of 2006, 572 patients were identified. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated by hazard ratios derived from Cox proportional hazards regression models. Compared with never-drinkers, regular alcohol drinkers (>150 g of ethanol/week) had a higher risk of the development of breast cancer; the multivariable-adjusted RRs were 1.75 (95% CI 5 1.16-2.65; p trend 5 0.035) for overall, 1.78 (95% CI 5 1.09-2.90) for premenopausal and 1.21 (95% CI 5 0.53-2.75) for postmenopausal women. There was no statistical evidence for effect modification by menopausal status, use of exogenous estrogens, intakes of isoflavone and folate, body weight, alcohol-induced facial flushing or smoking (All p interactions ! 0.15). Excessive alcohol intake was associated with an increase in the risk of breast cancer in this population. There was no statistical evidence for effect modification.Alcohol-related carcinogenesis of the breast has been identified in a number of animal and epidemiological studies, and confirmed by the International Agency for Research on Cancer (IARC) working group, 1,2 the Second Expert Report from the World Cancer Research Fund, 3 and meta-analyses. 4,5 Apparently consistent with this, the steep increase in the incidence of breast cancer in Japan over the last 3 decades 6 has coincided with an upward trend in alcohol consumption, 7 although other explanations may include increased height, early menarche, low birthrate or late first birth. [8][9][10][11] Nevertheless, a recent qualitative review 12 of 11 epidemiological studies conducted in Japanese women suggested that the association remains inconclusive, albeit that one prospective study in 35,844 women, including 151 cases, reported a positive association. 13 Proposed mechanisms of ethanol-associated breast carcinogenesis include both hormone-dependent 14-19 as well as hormone-independent carcinogenic pathways, such as the induction of carcinogenesis, mutagenesis and DNA damage by acetaldehyde, a toxic ethanol metabolite; reactive oxygen species and an effect on one carbon metabolism, which is involved with folate level and vitamin B intake. [20][21][22][23][24] Although the results of a meta-analysis 5 supported both pathways by showing a positive association for estr...

Alcohol Consumption and Breast Cancer Risk According to Hormone Receptor Status in Japanese Women: A Case-Control Study

“…In our study, approximately 75% of ever drinkers among the controls drank beer (data not shown in tables). This frequency differed from not only those in American and European populations (Allen et al 2009;Li et al 2009) but also that in the Japanese population (Suzuki et al 2010). In the JHPC study population, the proportion of beer drinkers was low, whereas beverages containing high level of alcohol such as sake and shochu were preferably consumed (Suzuki et al 2010).…”

“…This frequency differed from not only those in American and European populations (Allen et al 2009;Li et al 2009) but also that in the Japanese population (Suzuki et al 2010). In the JHPC study population, the proportion of beer drinkers was low, whereas beverages containing high level of alcohol such as sake and shochu were preferably consumed (Suzuki et al 2010). Alcoholic beverages contain several chemicals, and it is possible that these chemicals may have different effects on receptor-specific risk (Scoccianti et al 2014).…”

“…A qualitative review of such Japanese studies, including three cohort studies and eight case-control studies, found an increased risk among drinkers in three of them (Kato et al 1989;Hirose et al 1995;Lin et al 2005), whereas the remaining studies found no such risk elevation. Subsequent studies including the Japan Public Health Center-based Prospective Study (JPHC Study) (Suzuki et al 2010) and a case-control study conducted in Aichi (Islam et al 2013) demonstrated a positive association between alcohol drinking and breast cancer risk. On the other hand, some previous epidemiological studies including those targeting Asian-American or Chinese women (Li et al 2011;Zhang and Holman 2011;Wu et al 2012) have shown an inverse association or no association between alcohol consumption and breast cancer risk.…”

“…However, there have been variations in receptor-specific risk among recent studies. For example, the JPHC Study conducted in Japan demonstrated an increased risk of ER+/PgR+ cancer among heavy drinkers (> 150 g of ethanol per week); however, the trend test showed non-significance (Suzuki et al 2010). In the cohort study conducted by the National Institutes of Health (NIH), alcohol consumption was significantly and positively associated with the risk of ER+/PgR+ cancer; however, the relative risks for ER+/PgR− and ER−/PgR− were non-significant (Lew et al 2009).…”

“…However, evidence for alcohol-related breast cancer risk in relation to hormone receptor status has been limited in both Japan and Western countries. In Japan, three studies have investigated alcohol-related breast cancer risk stratified by hormone receptor status (Yoo et al 1997;Suzuki et al 2010;Islam et al 2013); however, information on hormone receptor status was incomplete among these three studies.…”