Abstract

Abstract Background: Dietary intake of isothiocyanates (ITC), found in high concentrations in cruciferous vegetables, has been suggested as a protective factor against the development of cancer at various sites including the colon, lung, and urinary bladder in humans. Epidemiologic evidence of association between dietary intake of ITC and risk of hepatocellular carcinoma (HCC), however, remains scant. One of the proposed routes of ITC protection may be through its modification of phase I and II detoxification enzymes. Some studies have shown that this modifying effect may vary by sex. Methods: We prospectively examined the association between dietary intake of ITC at baseline and the risk of developing HCC in the Singapore Chinese Health Study, a cohort of 63,257 middle-aged and older Chinese men and women enrolled between 1993 and 1998. Dietary intake of ITC was derived from a validated, semi-quantified comprehensive food frequency questionnaire administered to subjects in person by trained interviewers at baseline. We had complete follow-up for incidence of cancer and death among cohort participants through computer linkage to databases of the population-based death and cancer registries. As of 31 December 2007, 394 cohort participants who were free of cancer at baseline developed HCC. The diagnoses of all HCC cases were verified through manual review of pathological reports and medical records. The hazard ratio (HR) and its 95% confidence interval (CI) for HCC with dietary ITC intake were estimated using a Cox proportional hazards model. Results: High intake of dietary ITC was associated with a reduced risk of HCC in men, but no protective effect was observed in women. Compared with the lowest tertile of ITC intake, men in the highest tertile of ITC experienced a 30% reduction in risk of developing HCC (HR=0.70, 95% CI = 0.51-0.97). After excluding HCC cases which occurred within two years post-enrollment, the inverse ITC-HCC risk association strengthened. The HRs (95% CIs) for the second and third tertiles of ITC were 0.97 (0.72-1.30) and 0.66 (0.46-0.94), respectively, when compared with the lowest tertile of intake (P for trend = 0.03). Dietary indole-3-carbinol, another breakdown product of glucosinolate, glucobrassicin, also found in high concentrations in cruciferous vegetables, was not significantly associated with risk of HCC in either men or women. Among those cases which occurred with more than two years follow-up, a statistically significant interaction between sex and ITC intake (p=0.01) was observed. Conclusion: High intake of dietary ITC led to a reduced incidence of HCC in men. The gender differential effect of ITC on HCC development suggests that ITC might have influence on the metabolism of sex hormones that have differential impact on HCC between men and women. 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 2817.

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