Abstract 5515: An investigation of risk factors for renal cell carcinoma by histologic subtype in two case-control studies
Authors: Purdue Mark P. , Moore Lee , Merino Maria J. , Boffetta Paolo , Colt Joanne S. , Schwartz Kendra L. , Bencko Vladimir , Davis Faith G. , Graubard Barry , Janout Vladimir , Ruterbusch Julie J. , Beebe-Dimmer Jennifer , Cote Michele , Shuch Brian , Mates Dana , Hofmann Jonathon N. , Foretova Lenka , Rothman Nathaniel , Szeszenia-Dabrowska Neonilia , Matveev Vsevolod , Wacholder Sholom , Zaridze David , Linehan W. Marston , Brennan Paul , Chow Wong-Ho 
Published: August 2012

Abstract
BACKGROUND: Renal cell carcinoma (RCC) is made up of several histological subtypes, the most common of which include clear cell, papillary and chromophobe RCC. These subtypes possess distinct genetic and clinical characteristics, and may also differ in etiology. To better understand whether the associations with established RCC risk factors [body mass index (BMI), smoking, hypertension, family history of kidney cancer] differ across subtypes, we conducted analyses in two large case-control studies conducted in the U.S. (1,217 cases, 1,235 controls) and Central and Eastern Europe (1,097 cases, 1,476 controls). METHODS: Histology was ascertained for 706 U.S. cases (58% of participating cases) and 891 European cases (81%) through a central pathology review conducted by a single pathologist. For cases not included in the central review, histology was abstracted from the original diagnostic pathology report. Case-only analyses were performed to compute odds ratios (OR) and 95% confidence intervals (CI) summarizing subtype differences by age, sex, and race. Case-control analyses were performed to compute subtype-specific ORs for other risk factors using polytomous regression. RESULTS: In case-only analyses, papillary cases (N=237) were older (OR=1.2, 95% CI=1.1-1.4 per 10-year increase), less likely to be female (OR=0.5, 95 % CI=0.4-0.8) and more likely to be black (OR=2.6, 95% CI=1.8-3.9) compared to clear cell cases (N=1,524). In case-control analyses, BMI was associated with clear cell (OR=1.5, 95% CI=1.3-1.7 per 10 kg/m2 increase) and chromophobe RCC (N=80; OR=1.5, 95% CI=1.1-2.0), but not papillary RCC (OR=1.1, 95% CI 0.9-1.5; heterogeneity test vs. clear cell, P=0.006). No differences across subtypes were observed for other risk factors. Analyses stratified by study and restricted to cases included in the central pathology review yielded virtually identical findings. CONCLUSIONS: Our results from this analysis, to our knowledge the most comprehensive investigation of etiologic heterogeneity across RCC histologic subtypes conducted to date, support the existence of distinct age, sex and racial distributions for RCC subtypes, and suggest that the obesity-RCC association differs by histology. These findings underscore the importance of accounting for histologic subtype in investigations of RCC etiology.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5515. doi:1538-7445.AM2012-5515