Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer
Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer
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DOI：
10.1111/j.1530-0277.2006.00334.x
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发表时间：
2007-03-01
影响因子：
3.2
通讯作者：
Helzlsouer, Kathy J.
中科院分区：
文献类型：
--
作者：
Visvanathan, Kala;Crum, Rosa M.;Helzlsouer, Kathy J.
背景资料：在体外，由ADH 1C（*）1或ADH 1B（*）2等位基因纯合基因编码的人类同工酶将乙醇代谢为乙醛的速率比ADH 1C（*）2或ADH 1B（*）1等位基因纯合基因更快。由于酒精是乳腺癌的一个已知的危险因素，我们评估了ADH和酒精消费量的遗传变异与乳腺癌的联合关联。方法：对321例病例和匹配对照进行了巢式病例对照研究。对ADH 1C和ADH 1B基因的5个单核苷酸多态性（SNP）进行基因分型。Logistic回归用于评估每个SNP的比值比（OR）和95%置信限（CI）。结果：饮酒者中，总酒精摄入量的中位数为13 g/wk（第10 - 90次饮酒; 4.5-135.9）的情况下和18 g/wk（第10 - 90次饮酒; 4.5-104.1）的控制。与不饮酒的女性相比，饮酒的女性患乳腺癌的风险往往增加（OR= 1.40%，95%CI 0.97-2.03），尤其是那些在乳腺癌诊断时绝经前的女性（OR= 2.69%，95%CI：1.00-7.26）。在已知的功能等位基因中，与每个基因座上基因型纯合子相比，至少有1个ADH 1C（*）1或ADH 1B（*）2等位基因的携带者患乳腺癌的风险没有显著增加。然而，在ADH 1B IVS 1 + 896 A> G位点遗传G等位基因的女性中，乳腺癌的风险倾向于较低（OR=0.62，95%CI 0.37-1.04）。总体单倍型频率没有显着不同的情况下和controls.Conclusions：在这项研究中，低水平的酒精与乳腺癌的风险是不改变已知的功能等位基因变体ADH 1B和1C基因的适度增加。ADH 1B IVS 1 + 896 A> G等位基因所赋予的保护性关联需要进一步评估。
Background: In vitro, human isoenzymes encoded by genes homozygous for the ADH1C(*)1 or ADH1B(*)2 alleles metabolize ethanol to acetaldehyde at a faster rate than those homozygous for the ADH1C(*)2 or ADH1B(*)1 allele. Because alcohol is a known risk factor for breast cancer, we evaluated the joint association of genetic variants in ADH and alcohol consumption in relation to breast cancer.Methods: A nested case-control study of 321 cases and matched controls was conducted. Five single nucleotide polymorphisms (SNPs) in the ADH1C and ADH1B genes were genotyped. Logistic regression was used to assess odds ratios (ORs) and 95% confidence limits (CIs) for each SNP. Haplotype analysis of all 5 SNPs was also undertaken.Results: Among drinkers, the median intake of total alcohol was 13 g/wk (10th-90th percentiles; 4.5-135.9) in cases and 18 g/wk (10th-90th percentiles; 4.5-104.1) in controls. Women who drank alcohol tended to be at an increased risk of developing breast cancer compared with those who did not drink (OR=1.40%, 95% CI 0.97-2.03), particularly those who were premenopausal at the time of breast cancer diagnosis (OR=2.69%, 95% CI: 1.00-7.26). Of the known functional alleles, breast cancer risk was not significantly increased among carriers of at least 1 ADH1C(*)1 or ADH1B(*)2 allele, when compared with those homozygous for the genotype at each locus. However, breast cancer risk tended to be lower among women who inherited the G allele at ADH1B IVS1+896A > G (OR=0.62, 95% CI 0.37-1.04). Overall haplotype frequencies were not significantly different between cases and controls.Conclusions: In this study low levels of alcohol are associated with a modest increase in breast cancer risk that is not altered by known functional allelic variants of the ADH1B and 1C gene. The protective association conferred by the G allele at ADH1B IVS1+896A > G needs further evaluation.