Urinary Isothiocyanates; Glutathione S-Transferase M1, T1, and P1 Polymorphisms; and Risk of Colorectal Cancer: The Multiethnic Cohort Study

Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, 1236 Lauhala Street, Honolulu, HI 96813, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 02/2009; 18(1):314-20. DOI: 10.1158/1055-9965.EPI-08-0627
Source: PubMed


Although an association between diet, especially cruciferous vegetables, and colorectal cancer has been hypothesized, recent studies have been inconsistent with their findings. One possibility for the discrepant results is that the interaction with related genes has not generally been considered. The present study examined the associations among urinary isothiocyanates, glutathione S-transferase (GST) polymorphisms, and colorectal cancer risk in a case-control study nested within the Multiethnic Cohort Study, based in Hawaii and Los Angeles, California. We measured prediagnositic urinary isothiocyanate levels adjusted for creatinine and analyzed GSTM1, GSTT1, and GSTP1 polymorphisms in 173 cases and 313 matched controls, with biospecimens collected between 2001 and 2006. Conditional logistic regression was used to compute odds ratios and 95% confidence intervals (95% CI). A detectable amount of urinary isothiocyanates was associated with a 41% decrease in colorectal cancer risk (95% CI, 0.36-0.98). No significant, main-effect associations were seen with a homozygous deletion of the GSTM1 or GSTT1 polymorphism, or with the AG or GG genotypes for GSTP1 rs1695. There was a weak suggestion that for individuals with the GSTP1 AG or GG genotype, a detectable amount of isothiocyanates further decreases one's risk of colorectal cancer compared with those with the GSTP1 AA genotype, but the interaction term was not statistically significant (P = 0.09). This is only the second study published on the association between urinary isothiocyanates and colorectal cancer risk. The results suggest that further studies, with larger numbers, examining a possible interaction with the GSTP1 polymorphisms are warranted.

Download full-text


Available from: Maarit Tiirikainen
  • Source
    • "Two control individuals for each case were randomly chosen from the women in the biospecimen subcohort who were alive and free of breast cancer at the age of the case's diagnosis, and who matched the case on birth year (± 1 year), race/ethnicity, location (Hawaii or California), date (± 6 months) and time (± 2 hours) of blood draw, fasting hours (8 to < 10 hours and 10+ hours), and hormone therapy use (current versus not current). Plasma concentrations of carotenoids, retinoids, and tocopherols were determined by high-pressure liquid chromatography with photodiode array detection from our earlier protocol [7,8], with slight modifications [6]. The median time from blood draw to date of diagnosis was 1 year and 5 months, with the middle 50% of subjects having follow-up time in the range of 8 months to 2.5 years. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Assessments by the handful of prospective studies of the association of serum antioxidants and breast cancer risk have yielded inconsistent results. This multiethnic nested case-control study sought to examine the association of plasma carotenoids, retinol, and tocopherols with postmenopausal breast cancer risk. Methods From the biospecimen subcohort of the Multiethnic Cohort Study, 286 incident postmenopausal breast cancer cases were matched to 535 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection and hours of fasting. We measured prediagnostic circulating levels of individual carotenoids, retinol, and tocopherols. Conditional logistic regression was used to compute odds ratios and 95% confidence intervals. Results Women with breast cancer tended to have lower levels of plasma carotenoids and tocopherols than matched controls, but the differences were not large or statistically significant and the trends were not monotonic. No association was seen with retinol. A sensitivity analysis excluding cases diagnosed within 1 year after blood draw did not alter the findings. Conclusions The lack of significant associations in this multiethnic population is consistent with previously observed results from less racially-diverse cohorts and serves as further evidence against a causal link between plasma micronutrient concentrations and postmenopausal breast cancer risk.
    Full-text · Article · Jul 2009 · Breast Cancer Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancer (CRC) is a multifactorial disease with dietary, lifestyle, and environmental exposures on one hand and genetic predispositions on the other hand. In this study, we examined the hypothesis of whether genetic polymorphisms in glutathione S-transferase M1 (GSTM1) and cytochrome P450 1A1 (CYP1A1) are related to the risk of developing CRC in Egyptian patients. The association of polymorphisms of CYP1A1 and GSTM1 with CRC was investigated in 40 patients (group I) and 40 controls (group II) using multiplex PCR for GSTM1 and PCR-RFLP for CYP1A1 polymorphism detection. The GSTM1 null genotype was more frequent in group I (45%) than in group II (35%), but this difference was not statistically significant [odds ratio (OR), 0.658 and the 95% confidence interval (CI), 0.217–1.997]. The relationship of GSTM1 deficiency and CRC risk was performed between both sexes; p = 0.213, tumor site p = 0.232, and pathological type p = 0.2, but none of them was statistically significant. The CYP1A1 variant genotype was more frequent in group II (25%) than in group I (10%), but this difference was not statistically significant (OR, 0.333 with the 95% CI, 0.078–1.416). The relationship of CYP1A1 and CRC risk was also performed between both sexes, p = 0.30, tumor site p = 0.329, and pathological type p = 0.16, but none of them was statistically significant. The results of this study suggest that neither the GSTM1 nor the CYP1A1 is associated with the risk of development of colorectal cancer in Egyptian patients.
    No preview · Article · Jan 2011 · Comparative Clinical Pathology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancer is the third most common form of cancer and the fourth most frequent cause of cancer deaths worldwide. Its development is influenced by both environmental and genetic factors. The glutathione S-transferase P1 gene (GSTP1) is a particularly attractive candidate for colorectal cancer susceptibility because it codes the enzyme involved in the metabolism of environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs). However, epidemiologic findings have been inconsistent. To investigate a putative association of GSTP1 Ile105Val polymorphism with the risk of colorectal cancer, we performed a meta-analysis and HuGE review of 16 published case-control studies (involving a total of 4386 colorectal cancer patients and 7127 controls). We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, the comparison of Val versus Ile allele showed no differential susceptibility to colorectal cancer (OR=0.98, 95% CI: 0.92-1.04). A protective effect was found in recessive, with an OR of 0.86 (95% CI: 0.76-0.98). Whereas no significant association was observed in either dominant or codominant model. In stratified subgroup analysis, no effect of Val allele was seen in subjects of Caucasian and Asian descent, and in healthy and hospital controls. In conclusion, the meta-analysis suggests that the GSTP1 Ile105Val polymorphism is unlikely to increase considerably the risk of sporadic colorectal cancer, and it should be confirmed in further studies.
    No preview · Article · Aug 2009 · European journal of cancer (Oxford, England: 1990)
Show more