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

• Published in: International journal of cancer 2018-02, Vol.142 (4), p.747-756
• Main Authors: Antwi, Samuel O., Eckel‐Passow, Jeanette E., Diehl, Nancy D., Serie, Daniel J., Custer, Kaitlynn M., Wu, Kevin J., Cheville, John C., Thiel, David D, Leibovich, Bradley C., Parker, Alexander S.
• Format: Article
• Language: English
• Subjects: alcohol; Alcohol dehydrogenase; alcohol metabolism genes; Alcohol use; Alcoholic beverages; Alcohols; Alleles; Cancer; Dehydrogenase; Dehydrogenases; Drinking behavior; gene–environment interaction; Health risk assessment; Health risks; Kidney cancer; Medical research; RCC; Renal cell carcinoma; Risk factors; Variation
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.31103

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) (pinteraction = 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. What's new? Drinking alcohol can reduce kidney cancer risk, but is that true for everyone? These authors looked at alcohol consumption, renal cell carcinoma risk and variants in alcohol metabolizing genes ADH6 and ADH7. They pinpointed a variant of the ADH7 gene that might activate alcohol's benefits: people with two copies of the common allele could reduce their RCC risk with alcohol consumption; those with one copy experienced a smaller benefit. For those lacking the allele, drinking alcohol did not lower RCC risk. The authors also showed that alcohol's protection comes in moderation. Up to two drinks daily lowered RCC risk; beyond that, they saw no additional benefit.