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

Samuel Antwi, Jeanette E Eckel-Passow, Nancy D. Diehl, Daniel J. Serie, Kaitlynn M. Custer, Kevin J. Wu, John Cheville, David D. Thiel, Bradley Leibovich, Alexander Parker

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StateAccepted/In press - 2017

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Alcohol Dehydrogenase
Renal Cell Carcinoma
Alcohol Drinking
Alcohols
Genes
Alleles
Odds Ratio
Confidence Intervals
Case-Control Studies
Logistic Models

Keywords

  • Alcohol
  • Alcohol metabolism genes
  • Gene-environment interaction
  • Kidney cancer
  • RCC
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Alcohol consumption, variability in alcohol dehydrogenase genes and risk of renal cell carcinoma. / Antwi, Samuel; Eckel-Passow, Jeanette E; Diehl, Nancy D.; Serie, Daniel J.; Custer, Kaitlynn M.; Wu, Kevin J.; Cheville, John; Thiel, David D.; Leibovich, Bradley; Parker, Alexander.

In: International Journal of Cancer, 2017.

Research output: Contribution to journalArticle

Antwi, Samuel ; Eckel-Passow, Jeanette E ; Diehl, Nancy D. ; Serie, Daniel J. ; Custer, Kaitlynn M. ; Wu, Kevin J. ; Cheville, John ; Thiel, David D. ; Leibovich, Bradley ; Parker, Alexander. / Alcohol consumption, variability in alcohol dehydrogenase genes and risk of renal cell carcinoma. In: International Journal of Cancer. 2017.
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abstract = "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.",
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AU - Custer, Kaitlynn M.

AU - Wu, Kevin J.

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AB - 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.

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