Abstract B79: Tobacco smoking, polymorphisms in xenobiotic metabolism enzyme genes, and prostate cancer risk and survival

Abstract

Introduction: The association between tobacco smoking and prostate cancer (PCa) risk and progression remains unclear. This study examined the association between tobacco smoking and risk of localized and advanced PCa, PCa-specific mortality, and overall mortality in African-American, Hispanic and non-Hispanic White men. Polymorphisms in xenobiotic metabolism enzyme genes were further examined as possible modifiers of associations with smoking.

Methods: Using data from the California Collaborative Prostate Cancer Study, a multiethnic population-based case-control study conducted in Los Angeles County (631 advanced and 533 localized cases; 594 controls) and the San Francisco Bay Area (568 advanced and 208 localized cases; 545 controls), we evaluated associations between tobacco smoking and risk of localized and advanced PCa using conditional logistic regression. Cox proportional hazards regression models and Kaplan Meier curves with log-rank tests were used to assess associations with PCa-specific and all-cause mortality. Median follow-up time for cases was 8.8 years (IQR: 6.2-9.9). We also investigated the role of 12 metabolism enzyme single nucleotide polymorphisms from 7 genes as potential modifiers of the relationship between tobacco smoking and PCa risk and progression using interaction models.

Results: After adjusting for age, PCa family history, body mass index, alcohol consumption, intake of meat cooked at high temperature, and use of snuffing/chewing tobacco, non-Hispanic Whites who were former smokers had an increased risk of localized PCa when compared to never smokers (OR=1.52, 95%CI: 1.11-2.09, p<0.01). Risk increased with younger age at first tobacco use (p-trend<0.01), duration of tobacco smoking (p-trend=0.01), number of daily cigarettes smoked (p-trend=0.02), and cigarette pack-years (p-trend=0.03). Current smoking was associated with an increased risk of advanced PCa (OR=1.41, 95%CI: 1.02-1.94, p=0.037) among non-Hispanic Whites, but a decreased risk among Hispanics (OR=0.48, 95%CI: 0.23-0.99, p=0.047). No significant trends were seen for any of the smoking variables among Hispanics or African-Americans. A CYP1A2 polymorphism (rs7662551) modified the relationship between smoking status and PCa risk; the addition of each C-allele increased risk for localized (p-interaction=0.01) and advanced (p-interaction=0.03) PCa, particularly among current smokers. Tobacco smoking was not associated with PCa-specific mortality. For all-cause mortality, increased risk was associated with current smoking, duration of smoking, cigarette pack-years, and young age at first smoking. Kaplan Meier survival probabilities for current smokers were 77% from all-cause mortality and 89% from PCa-specific mortality.

Conclusions: We observed that tobacco smoking was associated with risk of localized and advanced PCa primarily among Non-Hispanic Whites. Moreover, we observed that tobacco smoking was associated with all-cause mortality, albeit no associations were observed for PCa-specific mortality. Genetic variation in CYP1A2 seems to modify the relationship of tobacco smoking status and PCa risk, but not mortality.

Citation Format: Ahva Shahabi, Roman Corral, Chelsea Catsburg, Amit D. Joshi, Jocelyn Koo, Esther M. John, Sue A. Ingles, Mariana C. Stern. Tobacco smoking, polymorphisms in xenobiotic metabolism enzyme genes, and prostate cancer risk and survival. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B79.