Etiologic heterogeneity of clear-cell and papillary renal cell carcinoma in the Netherlands Cohort Study.

At present, mostly case-control and retrospective studies have investigated the association between etiologic risk factors and the development of histologic subtypes of renal cell carcinoma (RCC). Therefore, we assessed the heterogeneity between body mass index (BMI), cigarette smoking, alcohol consumption and hypertension across clear-cell RCC (ccRCC) and papillary RCC (pRCC) risk in the prospective Netherlands Cohort Study on diet and cancer (NLCS). In 1986, 120,852 participants aged 55-69 completed a self-administered questionnaire on diet and other risk factors for cancer. Participants were followed-up for cancer through record linkage. Tumor histology was assessed through centralized revision by two experienced uropathologists. After 20.3 years of follow-up, 384 histologically verified RCC cases, including 315 ccRCC and 46 pRCC cases, and 4144 subcohort members were eligible for case-cohort analysis. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated by multivariable-adjusted proportional hazards models. Overall, BMI was associated positively with ccRCC risk, but inversely with pRCC risk. Cigarette smoking was associated with an increased ccRCC, but a decreased pRCC risk. Alcohol consumption was inversely associated with both ccRCC and pRCC risk. Hypertension was associated with an increased risk of both ccRCC and pRCC. Statistically significant etiologic heterogeneity was observed for BMI, BMI change since age 20, and smoking duration in current smokers across ccRCC and pRCC risk. In conclusion, we observed potential heterogeneity for BMI, BMI change and smoking duration across ccRCC and pRCC risk. This article is protected by copyright. All rights reserved.

International journal of cancer. 2020 Jul 07 [Epub ahead of print]

J A A van de Pol, L George, P A van den Brandt, M M L L Baldewijns, L J Schouten

Department of Epidemiology, GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.