Abstract 1262: Established genetic variants and dietary patterns jointly impact risk of renal cell carcinoma in non-Hispanic whites

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Several emerging renal cell carcinoma (RCC) risk factors related to diet and energy balance have been identified; however, the etiology of RCC and potential mechanisms remain poorly described. Utilizing data collected in an ongoing case-control study, we identified dietary patterns associated with RCC risk. We further assessed whether these associations varied by known and suspected RCC risk factors, such as obesity, tobacco use, physical inactivity and hypertensive status, as well as established genetic variants identified through GWAS. Methods: Diet was assessed among 703 incident RCC cases recruited from the University of Texas MD Anderson Cancer Center in Houston, Texas and 746 healthy controls recruited via random digit dialing. We derived three primary dietary patterns: “fruits and vegetables”, an “American/Western” and a “Tex-Mex” pattern using factor analysis. We examined associations between dietary pattern scores and RCC risk and effect modification by obesity, smoking status, physical activity, history of hypertension and genetic variants. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using multivariate logistic regression adjusted for age, gender, total energy intake, and other RCC risk factors. Results: Greater adherence to the fruits and vegetables dietary pattern was inversely related to RCC risk [OR and 95% CI across tertiles: 1.00 (ref), 0.68 (0.51-0.86) and 0.55 (0.41-0.74), respectively; P-trend <0.001], while the American/Western dietary pattern was directly associated with RCC risk [1.00 (ref), 1.60 (95% CI: 1.19-2.15) and 1.96 (95% CI: 1.47-2.61); P-trend<0.001]. Results were consistent across various stratified analyses. We observed evidence of a significant synergistic interaction between the American/Western pattern and hypertensive status [highest vs. lowest tertile OR = 1.82 95% CI: 1.20-2.74 among individuals with no history of hypertension and highest vs. lowest tertile OR =2.14 95% CI: 1.42-3.23 among those with history of hypertension; additive Pinteraction= 0.01]. Variants in genes ITPR2, ZEB2, PDZD2 and CEP85L were also found to significantly interact with dietary patterns in relation to RCC risk. The strongest interaction was observed between rs718314 (ITPR2) and the American/Western dietary pattern (multiplicative Pinteraction =0.04; additive Pinteraction= 0.02). ITPR2 has previously been shown to be related to nutrient metabolism and central obesity. Conclusion: Dietary patterns, genetic variants, and host characteristics may individually and jointly influence susceptibility to RCC. Citation Format: Melkonian Stephanie, Carrie R. Daniel, Michelle Hildebrandt, Nizar Tannir, Yuanqing Ye, Wong-Ho Chow, Christopher Wood, Xifeng Wu. Established genetic variants and dietary patterns jointly impact risk of renal cell carcinoma in non-Hispanic whites. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1262. doi:10.1158/1538-7445.AM2014-1262