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

Alcohol consumption has been associated inversely with renal cell carcinoma (RCC) risk; however, no study has examined effect modification by germline variation in alcohol-metabolising genes. A study 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 analysed. Alcohol intake was assessed using a standardised 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.

The researchers observed effect modification by variation in rs1154454 (ADH7) 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 Renal Cell Carcinoma risk. However, consuming more than two drinks a day negates this protective effect. The authors conclude that the association between alcohol intake and RCC risk appears to be modulated by inter-individual germline variation in alcohol-metabolising genes.

Source: Alcohol consumption, variability in alcohol dehydrogenase genes and risk of renal cell carcinoma. Antwi SO, Eckel-Passow JE, Diehl ND, Serie DJ, Custer K, Wu KJ, Cheville JC, Thiel DD, Leibovich BC, Parker AS. Int J Cancer. 2017 Oct 12. doi: 10.1002/ijc.31103.

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