Abstract 910: Isothiocyanate-gene interactions and endometrial cancer risk: the California Teachers Study

Abstract

Abstract Background: Cruciferous vegetables may reduce the risk of endometrial cancer, although the evidence is mixed. However, as observed for other cancers, this association may be modified by polymorphic variation in phase I genes (e.g., CYP1A1 which also controls estrogen metabolism) and phase II genes (e.g., GSTs). Such interactions have not been previously examined for endometrial cancer. Methods: A nested case-control study of type 1 invasive endometrial cancer was conducted within the California Teachers Study (CTS) cohort. 320 women (age≥50) with incident cancer, identified through the California Cancer Registry and diagnosed after joining the cohort and before January 2005, and 629 controls, frequency-matched on age, race/ethnicity, and broad geographic region of residence within California, provided a DNA sample and had complete epidemiologic data. Consumption of cruciferous vegetables was assessed using a validated food-frequency questionnaire at the time women joined the cohort in 1995-96. Isothiocyanate (ITC) consumption was estimated using values obtained from prior analysis of California foods and was based on frequency and portion size of usual consumption of cruciferous vegetables. Selected single nucleotide polymorphisms (SNP) in several phase I and II genes were genotyped. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for matching variables. Results: Neither cruciferous vegetable or ITC intake, nor variants in CYP1A1 MspI (rs4646903), GSTM1, or GSTT1 were directly associated with endometrial cancer risk. The Val/Val genotype of GSTP1 Ile105Val was associated with increased endometrial cancer risk (OR=1.64, 95% CI: 1.07-2.53) and the Val/Val genotype of CYP1A1 Ile462Val was associated with reduced risk (OR=0.63, 95% CI: 0.37-1.08). There was no interaction, however, between cruciferous vegetable or ITC intake and any of these genes. Conclusion: Consistent with some, but not all, previous studies we observed a significant reduction in risk associated with the Val/Val genotype of CYP1A1 Ile462Val. This study also confirms a single previous, but smaller report of an association between type I endometrial cancer and the Ile105Val SNP in GSTP1. However, while the prospective assessment of dietary intake minimizes recall bias, we found no evidence of an interaction between these genetic variants and ITC consumption. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 910.