Gene-environment interactions in renal cell carcinoma.
The majority of renal cell carcinomas (RCCs) are sporadic, and increasing incidence rates suggest that such environmental risk factors as smoking play a role in the etiology of the disease. Cases with RCC were selected from the population-based cancer registry of Orange County, California, between 1994 and 1997; controls were recruited by telephone using random digit dialing. A total of 115 case and 259 control subjects were genotyped for N-acetyltransferase 2 (NAT2), which codes for a polymorphic enzyme involved in tobacco-carcinogen metabolism. Subjects with slow acetylator genotypes were found to be at twofold increased risk (odds ratio (OR) = 1.8; 95 percent confidence interval (CI): 1.1, 2.9) of RCC. Although cancer risk doubled among smokers (OR = 2.2; 95 percent CI: 1.3, 3.7), stratified analysis revealed gene-environment interaction among slow acetylators that smoked (OR = 3.2; 95 percent CI: 1.7, 6.1) compared with rapid acetylators that smoked (OR = 1.4; 95 percent CI: 0.7, 2.9). A dose response was found for pack-years among slow acetylators (p < 0.01) but not among rapid acetylators (p = 0.06). Although smoking is a well-established risk factor of RCC, our data suggest that the risk is pronounced among slow rather than rapid acetylators.
Semenza
J C
JC
School of Community Health, College of Urban and Public Affairs, Portland State University, Portland, OR 97207-0751, USA. semenzaj@pdx.edu
Ziogas
A
A
Largent
J
J
Peel
D
D
Anton-Culver
H
H
D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002140:California / Q000453:epidemiology; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D017678:Sex Distribution; D012907:Smoking / Q000009:adverse effects
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human