Alcohol consumption, variability in alcohol dehydrogenase genes and risk of renal cell carcinoma

被引:12
作者
Antwi, Samuel O. [1 ]
Eckel-Passow, Jeanette E. [2 ]
Diehl, Nancy D. [1 ]
Serie, Daniel J. [1 ]
Custer, Kaitlynn M. [1 ]
Wu, Kevin J. [3 ]
Cheville, John C. [3 ]
Thiel, David D. [4 ]
Leibovich, Bradley C. [5 ]
Parker, Alexander S. [1 ]
机构
[1] Dept Hlth Sci Res, 4500 San Pablo Rd, Jacksonville, FL USA
[2] Dept Hlth Sci Res, 200 1st St SW, Rochester, MN USA
[3] Dept Lab Med & Pathol, 4500 San Pablo Rd, Jacksonville, FL USA
[4] Mayo Clin, Dept Urol, 4500 San Pablo Rd, Jacksonville, FL USA
[5] Mayo Clin, Dept Urol, 200 1st St SW, Rochester, MN USA
关键词
alcohol; alcohol metabolism genes; kidney cancer; renal cell carcinoma; RCC; gene-environment interaction; DOSE-RESPONSE METAANALYSIS; GENOME-WIDE ASSOCIATION; CANCER-RISK; IN-VITRO; POSTMENOPAUSAL WOMEN; SUSCEPTIBILITY LOCI; RISING INCIDENCE; KIDNEY CANCER; UNITED-STATES; ADH7; GENE;
D O I
10.1002/ijc.31103
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Alcohol consumption has been associated inversely with renal cell carcinoma (RCC) risk; however, no study has examined effect modification by germline variation in alcohol-metabolizing genes. We investigated whether the association between alcohol intake and RCC risk is modulated by germline variants in alcohol dehydrogenase genes in a large case-control study. Data from 652 RCC cases and 1,366 non-cancer controls were analyzed. Alcohol intake was assessed using a standardized risk factor questionnaire. Three previously genotyped polymorphisms in ADH6 and ADH7 with the TaqMan assay were examined. Odds ratios (ORs) and 95% confidence interval (CI) were calculated using logistic regression, adjusting for covariates. Compared to non-drinkers, ever consumption of alcohol was associated with lower RCC risk (OR=0.52, 95% CI=0.42-0.65). Analysis with cubic spline regression curve showed a "J-shaped" relationship between alcohol drinks/day and RCC risk, such that there was no added benefit against RCC for consumption of more than two drinks/day. We observed effect modification by variation in rs1154454 (ADH7) (p(interaction)=0.007); a per unit increase in alcohol drink/day was associated with 35% lower RCC risk among non-minor allele carriers, a 27% lower risk among those who carry one copy of the minor allele, but no association was observed among those with two copies of the minor allele. These findings indicate that alcohol consumption is associated with lower RCC risk. Consuming more than two drinks a day does not confer additional protection against RCC. The association between alcohol intake and RCC risk appears to be modulated by inter-individual germline variation in alcohol-metabolizing genes.
引用
收藏
页码:747 / 756
页数:10
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