Abstract
The associations between genetic polymorphisms in ADH1B (rs1229984) and ALDH2 (rs671), alcohol consumption, the effect of a combination of the two polymorphisms, and breast cancer risk were studied in a population of East-Asian women. In this study, 623 breast cancer cases and 1845 controls, aged 40 or above, were included. The association between ALDH2 polymorphism and breast cancer risk was validated in 2143 breast cancer cases and 3977 controls. Alcohol consumption increased the risk of breast cancer regardless of ADH1B and ALDH2 genotypes. The rs671 polymorphism of ALDH2 was independently associated with increased breast cancer risk (OR = 1.27, 95% CI = 1.02–1.58 per increment of A). The ADH1B rs1229984 polymorphism, and combined effects of the rs671 and rs1229984 polymorphisms, did not reveal any significant association with breast cancer. Stratification by menopausal status revealed that rs671 gene polymorphisms were significantly associated with breast cancer only in postmenopausal women (OR = 1.45, 95% CI = 1.03–2.05 per increment of A). This is the first study to demonstrate an independent association between ALDH2 gene variants and breast cancer in Asian women. Further studies are warranted to further elucidate the etiology of breast cancer as it relates to alcohol consumption in Asian women.
Highlights
Alcohol consumption is a major risk factor that adversely affects the health of people worldwide[1]
The rs[671] genotype, unassociated with breast cancer in an adjusted model, was significantly associated with breast cancer risk after the model was adjusted for daily alcohol intake in patients with a GA or AA genotype compared with those presenting a GG homozygote (OR = 1.29, 95% CI = 1.00–1.65, P-value = 0.045) and per increment of A (OR = 1.27, 95% CI = 1.02–1.58, P-value = 0.032)
The combined effects of the ALDH2 rs[671] and ADH1B rs1229984 polymorphisms are presented in Appendix Table 2
Summary
Alcohol consumption is a major risk factor that adversely affects the health of people worldwide[1]. Gene variants involved in alcohol metabolism and detoxification are thought to affect the genetic susceptibility to alcohol-associated cancers. Epidemiological and animal studies have consistently correlated high alcohol intake with increased breast cancer risk in women[2]; the gene variants involved in alcohol metabolism or detoxification have only been inconclusively associated with breast cancer risk[8,9]. In the present study, we investigated the association among genetic, functionally established single nucleotide polymorphisms (SNPs) in ADH1B (rs1229984) and ALDH2 (rs671), alcohol consumption, and their combined effects and breast cancer risk in an East-Asian population
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