The incidence of kidney/renal pelvis cancers has increased substantially over the last twenty years, suggesting environmental risk factors such as tobacco use in the etiology of the disease. We genotyped kidney/renal pelvis cancer cases and controls for N-acetyltransferase 2 (NAT2) which is polymorphic in the population and is involved in tobacco carcinogen metabolism. We found individuals with slow acetylator NAT2 genotypes to be at a twofold increased risk (odds ratio [OR]=1.9; 95% confidence interval [CI]=1.1-3.1) for kidney/renal pelvis cancer, presumably due to reduced NAT2 enzyme activity. Although the risk for kidney/renal pelvis cancer was doubled among smokers (OR=2.3; 95%CI 1.4-3.7), stratified analysis revealed that this risk was confined to slow NAT2 acetylators that smoked (OR=3.8; 95% CI=1.9-7.6) rather than rapid acetylators that smoked (OR=1.3; 95% CI=0.6-2.7). A dose-response relationship was found for pack-years among slow acetylators (p<0.01) but not among rapid acetylators (p=0.06). A large proportion (72%) of the cancers studied were attributed to gene-environment interaction between the polymorphic variant and smoking. The gene-environment interaction was particularly pronounced among women smokers with a synergy index of 15.7, as a measure of the strength of interaction. These data illustrate the importance of genetic susceptibility and environmental exposures in the etiology of kidney/renal pelvis cancer in the general population. Although smoking is a well-established risk factor for kidney/renal pelvis cancer, our data suggest that the risk is restricted to slow acetylators rather than rapid acetylators.
Learning Objectives: recognize role of gene- environment interactions in cancer risk take action for prevention of cancer through environmental exposure
Presenting author's disclosure statement:
Organization/institution whose products or services will be discussed: none
I do not have any significant financial interest/arrangement or affiliation with any organization/institution whose products or services are being discussed in this session.