Interaction of the effects of alcohol drinking and polymorphisms in alcohol-metabolizing enzymes on the risk of female breast cancer in Japan.
BACKGROUND
Epidemiological studies consistently indicate that alcoholic beverages are an independent risk factor for female breast cancer. Although the mechanism underlying this effect remains unknown, the predominant hypothesis implicates mutagenesis via the ethanol metabolite acetaldehyde, whose impact on the carcinogenesis of several types of cancer has been shown in both experimental models and molecular epidemiological studies. Many of the epidemiological studies have investigated genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) His48Arg and aldehyde dehydrogenase-2 (ALDH2) Glu504Lys, because of the strong impact these polymorphisms have on exposure to and accumulation of acetaldehyde. With regard to breast cancer, however, evidence is scarce.


METHODS
To clarify the impact on female breast cancer risk of the interaction of the effects of alcohol consumption and polymorphisms in the alcohol-metabolizing enzymes ADH1B and ALDH2, we conducted a case-control study of 456 newly and histologically diagnosed breast cancer cases and 912 age- and menopausal status-matched noncancer controls. Gene-gene and gene-environment interactions between individual and combined ADH1B and ALDH2 gene polymorphisms and alcohol consumption were evaluated.


RESULTS
Despite sufficient statistical power, there was no significant impact of ADH1B and ALDH2 on the risk of breast cancer. Neither was there any significant gene-environment interactions between alcohol drinking and polymorphisms in ADH1B and ALDH2.


CONCLUSIONS
Our findings do not support the hypothesis that acetaldehyde is the main contributor to the carcinogenesis of alcohol-induced breast cancer.
Kawase
Takakazu
T
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
Matsuo
Keitaro
K
Hiraki
Akio
A
Suzuki
Takeshi
T
Watanabe
Miki
M
Iwata
Hiroji
H
Tanaka
Hideo
H
Tajima
Kazuo
K
D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000428:Alcohol Drinking / Q000009:adverse effects*; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D000431:Ethanol / Q000378:metabolism; D005260:Female; D006304:Health Status; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
D000431:Ethanol; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial