In this population of Asian-American women with breast cancer, we assessed the impact on breast cancer risk of two common modifiable exposures, alcohol and tobacco use, to determine whether they partially explained the 6-fold gradient in risk by acculturation in this migrant population. Alcohol consumption is an accepted risk factor for breast cancer. Several pooled and meta-analyses, as well as most recent studies, have found evidence of a dose-response relationship that appears at modest intake (approximately 1 drink per day), with risk increasing 3% – 12% for each 10 g of alcohol (approximately one drink) consumed per day [9
]. Questions still remain, however, about the shape of the dose-response curve, especially at low levels of intake (< 1 drink per day) [14
Similar to a large cohort study of women in the United Kingdom [19
], we found no excess breast cancer risk associated with low levels of alcohol intake (< 5 g per day) in our study of Asian American women. But, we did find higher than expected risks (1.3–1.5) among women reporting recent alcohol intake of 5 – 20 g/day. However, these risk estimates have wide confidence intervals and are not statistically significant due to the relatively small number of users who drank one drink or more per week. Few studies that estimate breast cancer risk by quantity of alcohol intake in Asian or Asian-American populations have been published; those we have found were conducted in Japan. A recently published systematic review of cohort and case-control studies in Japanese populations that evaluated the relationship between alcohol drinking and breast cancer risk reported that results from both types of studies were inconsistent and often limited by study methodology [20
]. The authors stated that lack of information precluded evaluating the dose-response relationship for alcohol.
The metabolism of alcohol differs in Asian and White populations. This may explain why the elevation in breast cancer risk associated with moderate drinking is unusually high in our Asian-American women. The enzyme alcohol dehydrogenase (ADH) oxidizes ethanol to acetaldehyde, which is oxidized to acetic acid by aldehyde dehydrogenase (ALDH). Two of the three common ADH genes, ADH1B
, have polymorphisms (ADH1B
) that code for more active enzymes, increase acetaldehyde production, and are more prevalent in Asian populations [21
]. In addition, a polymorphism in the ALDH gene (ALDH2
) that codes for an essentially inactive form of ALDH is found in Asian but not White populations [21
]. These three polymorphisms, which would increase the acetaldehyde in circulation, are believed to be responsible for the flushing, discomfort, and nausea associated with heavy drinking in susceptible Asian individuals and the relatively low alcohol intake and low prevalence of alcoholism in Asian populations [23
]. Acetaldehyde, a known mutagen and carcinogen, may explain why alcohol intake increases the risk of breast cancer [25
]. Asian women who drank even small quantities of alcohol would receive greater exposure to acetaldehyde, compared with White women with similar or somewhat higher intake, which could explain the high, though not significant, risk of breast cancer we observed at modest levels of alcohol intake among the Asian-American women in our study. We were surprised that among the Asian-American women with the very highest intakes, 20+ g of alcohol/day, breast cancer risk dropped, but this estimate has wide confidence intervals and could be an unstable result based on small numbers. However, if this observation were accurate, it is conceivable that these women may be exposed to lower levels of acetaldehyde despite their higher alcohol consumption because they lack the polymorphisms that increase acetaldehyde levels and thus inhibit heavy drinking.
Other mechanisms, in addition to acetaldehyde production, have been proposed to explain why breast cancer risk is elevated at modest levels of alcohol consumption [19
]. It is plausible that these mechanisms of action could be influenced by the genetic differences in alcohol metabolism in Asian populations. The low percentage of Asian-American women in our study drinking 5+ g of alcohol/day (7.6% of controls) and the relatively high percentage of women characterizing themselves as never drinking (39.1% of controls) are consistent with other reports of alcohol use in Asian populations [20
Over the years, smoking has been postulated to increase the risk of breast cancer. While most epidemiologic studies have not supported an overall association, some questions, such as the influence of early initiation and long duration, remain unanswered [28
]. Also, recent evidence suggests that cigarette smoking is associated with an increased breast cancer risk among Caucasian and African American women with N-acetyltransferase 2
) slow acetylation genotypes which result in slow clearance of aromatic amines, a major class of tobacco carcinogens [30
]. However, we lacked the genotype data to evaluate such a finding in our study population. Among the Asian-American women in our study, we found no statistically significant increase in risk with ever having smoked and no consistent or significant trends in risk with duration or frequency of cigarette use. However, we did find a statistically significant elevation in risk among ex-smokers who had quit from 2–19 years and consistent with other reports [31
], we did find an increased risk associated with initiation of smoking during adolescence, a time when breasts are developing and breast cancer risk may be altered [36
]. The results of our smoking analysis agree with a collaborative reanalysis of pooled data from 53 epidemiologic studies that found no increased breast cancer risk among ever or current smokers that did not drink [14
Both alcohol and cigarette use were significantly higher in Asian-American women born in the West than in those born in the East, with the percentage of ever drinkers 30.3% higher and the percentage of ever smokers 190% higher. Among drinkers and smokers, the frequency of use did not vary substantially by place of birth. However, because the influence of alcohol and cigarettes on breast cancer risk was modest, these factors explain little of the 6-fold gradient in breast cancer risk associated with migration history and acculturation.
A limitation on estimating the influence of moderate to heavy intake of alcohol in this Asian population is the small percentage of subjects who drank 5 or more grams of alcohol per day. Also no information was available on different patterns of alcohol use that may have occurred over their lifetime. Strengths of this migrant study are that it is population-based and included a wide range of lifestyles and acculturation in Asian-American women. Also, this is the first study to examine the role of smoking and alcohol consumption, particularly low levels of intake, with data collected consistently from Asian-American women from the general population.
In conclusion, low alcohol intake was not related to increased breast cancer risk and neither alcohol nor cigarette use contributed to the striking increase in breast cancer risk with acculturation in these Asian-American women. In previous analyses we found that this increase also was not due to differences in menstrual or reproductive factors, anthropometry, or dietary intake of soy [4
]. However, in previous analyses of this case-control dataset, we were able to demonstrate that breast cancer incidence in Asian migrants to the United States has approached that of U.S. White women [3
]. Recent analyses have confirmed this finding in Japanese- and Filipino-American women [38
]. Thus, modifiable factors associated with Westernization are likely to play a major role in breast cancer etiology, and continued research is necessary to elucidate the responsible lifestyle and environmental exposures.