Abstract 2824: A prospective evaluation of dietary indole-3-carbinol in relation to risk of lung cancer in the Singapore Chinese Health Study

Background: Indole-3-carbinol (I3C) is a naturally occurring hydrolysis product of glucobrassicin, a glucosinolate in cruciferous vegetables. I3C has been demonstrated to modulate carcinogenesis in multiple organs including the breast in experimental animals. Data examining the relationship between dietary I3C or its precursors and breast cancer risk in humans are sparse. Methods: We prospectively examined the association between dietary intake of glucobrassicins and risk of breast cancer in the Singapore Chinese Health Study, a cohort of 63,257 middle-aged and older Chinese men and women enrolled between 1993 – 1998. Dietary intake of glucobrassicins was derived from a validated, semi-quantitative food-frequency questionnaire administered to subjects in person at enrollment and the quantified amount of glucobrassicins in specific cruciferous vegetables purchased from Singapore markets. We had complete follow-up for incidence of cancer and death among cohort participants via computer record linkage analysis to the nationwide Singapore cancer and death registries. As of December 31, 2007, 758 women developed breast cancer after 397,681 person-years of follow-up of the cohort. Cox proportional hazards regression was used to evaluate the association between dietary intake of glucobrassicins and breast cancer risk. The regression model included age, year of interview, dialect, level of education, BMI (kg/m2), daily alcohol drinking, family history of breast cancer, age when period became regular, number of live births and dietary isothiocyanate (ITC) precursor intake. Results: Overall there was no association between dietary I3C intake and breast cancer risk with or without adjustment for potential confounders. The null association was present in both pre-menopausal and post-menopausal women. After excluding cases of breast cancer that occurred within the first 5 years post enrollment, premenopausal women with high intake of glucobrassicins were at increased risk of breast cancer in a dose-dependent manner (Ptrend=0.03). Compared to the lowest quintile, hazard ratios (HR) [95% confidence intervals (CI)] for the 2nd, 3rd, 4th and 5th quintile of glucobrassicins were 2.09 (1.02-4.26), 2.98 (1.41-6.32), 2.65 (1.18-5.99) and 3.26 (1.36-7.81), respectively. No association between dietary glucobrassicins and breast cancer risk was observed in postmenopausal subjects. The present study did not show an inverse association between dietary ITC and breast cancer risk. Conclusion: High intake of dietary glucobrassicins was associated with increased incidence of breast cancer in premenopausal women. These findings suggest that I3C precursors may modulate hormonal metabolism that leads to increased risk of breast cancer in premenopausal women. Mechanistic studies are warranted to shed light on the observed association between dietary I3C and breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3731. doi:10.1158/1538-7445.AM2011-3731