Background: Meat-cooking mutagens, including heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs), are formed as a result of meat cooking, preparation, and level of doneness and may increase the risk of renal cell carcinoma (RCC). We utilized data from an ongoing case-control study to evaluate the association between meat-cooking mutagens and the risk of RCC. We assessed the modification of these associations by known and suspected RCC risk factors such as smoking, obesity, alcohol use, physical activity and hypertension as well as established genetic variants identified through genome-wide association studies (GWAS).

Methods: We investigated dietary intake of four meat-cooking mutagens among 659 incidence RCC cases recruited from the University of Texas MD Anderson Cancer Center in Houston, Texas and 699 healthy controls recruited via random digit dialing. We evaluate the association of PAH/HCA intake on RCC risk, and examined whether associations varied by known and suspected risk factors for RCC and genetic susceptibility variants previously identified from GWAS. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using tertiles of dietary PAH/HCA intake adjusting for total energy intake, fruit and vegetable intake, age, gender as well as known or suspected RCC risk factors.

Results: Dietary intake of the mutagenic compounds 2-amino-3,8-dimethylimidazo-[4,5-f] quinoxaline (MeIQx) and 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were significantly associated with an increased risk of RCC [(OR and 95%CI across tertiles:1.00 (ref), 1.28 (0.94-1.74), 1.95 (1.43-2.66); P-trend <0.001 and 1.00 (ref), 1.41 (1.04-1.90), 1.54 (1.14-2.07); P-trend = 0.02) respectively]. We observed evidence for interactions between PhIP and variants in two RCC susceptibility genes, ITPR2 (rs718314 multiplicative Pinteraction = 0.03, additive Pinteraction = 0.002) and EPAS1 (rs7579899 additive Pinteraction = 0.06), on modifying RCC risk.

Conclusions: Intake of meat may increase the risk of RCC through mechanisms related to the cooking compounds MeIQx and PhIP. These associations may be modified by genetic susceptibility variants related to RCC. Further research is necessary to understand the biological mechanisms underlying these interactions.

Citation Format: Stephanie C. Melkonian, Carrie R. Daniel, Yuanqing Ye, Nizar M. Tannir, Jose A. Karam, Surena F. Matin, Christopher G. Wood, Xifeng Wu. Gene-environment interaction of genome-wide association study-identified susceptibility loci and meat-cooking mutagens in renal cell carcinoma etiology. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 836. doi:10.1158/1538-7445.AM2015-836