Dataset Information

Urinary isothiocyanates; glutathione S-transferase M1, T1, and P1 polymorphisms; and risk of colorectal cancer: the Multiethnic Cohort Study.

ABSTRACT: 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.

SUBMITTER: Epplein M

PROVIDER: S-EPMC2715873 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Urinary isothiocyanates; glutathione S-transferase M1, T1, and P1 polymorphisms; and risk of colorectal cancer: the Multiethnic Cohort Study.

Epplein Meira M Wilkens Lynne R LR Tiirikainen Maarit M Dyba Marcin M Chung Fung-Lung FL Goodman Marc T MT Murphy Suzanne P SP Henderson Brian E BE Kolonel Laurence N LN Le Marchand Loïc L

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20090101 1

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 ...[more]

PMID: 19124514

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Project description:BackgroundGlutathione S-transferases (GSTs) play important roles in protecting cells against oxidative stress and toxic chemicals. This study aimed to investigate the distribution of GSTM1, GSTT1, and GSTP1 variants and their roles in periodontitis susceptibility in a Caucasian population.MethodsWe analyzed 406 participants, including 204 healthy controls and 203 periodontitis patients. A multiplex polymerase chain reaction (PCR) approach was used to analyze GSTM1 and GSTT1 loci. GSTP1 variants were detected by PCR-haplotyping method in a subgroup of participants (N = 350). Chi-square or Fisher´s exact tests were used to compare genotypic and allelic differences. The Bonferroni method was applied to correct for multiple comparisons (pcorr).ResultsThe GSTM1 genotype distribution did not differ significantly between controls and periodontitis patients (p = 0.44). Additionally, the wild/null genotypes of GSTT1, Ile105Val and Ala114Val frequencies of GSTP1 were not significantly different between the two groups after correction for multiple comparisons (p = 0.05, p = 0.55, p = 0.02, pcorr>0.05, respectively). The GSTM1 and GSTP1 Ile105Val gene variants were similarly distributed between non-smokers and smokers in both groups (p = 0.38, p = 0.20, and p = 0.14, p = 0.35, respectively). However, the wild genotype of the GSTT1 and Ala114Ala variant of the GSTP1 genes were present more frequently in non-smoking periodontitis patients than in non-smoking controls (p = 0.03, pcorr>0.05, and p = 0.009, pcorr>0.05, respectively) although their frequencies did not differ between smoking periodontitis patients and smoking controls (p = 0.23, p = 0.68, respectively).ConclusionsThis study in a Czech Caucasian population did not confirm a highly significant association between GST gene variants and susceptibility to periodontitis, as previously reported by Arshad and colleagues in Pakistanis. However, a weak relationship between GSTT1 and GSTP1 rs1138272 polymorphisms and periodontitis in non-smokers was observed.

Project description:Glutathione S-transferase (GST) genes as well as heme oxygenase 1 gene (HMOX1) encode enzymes that detoxify carcinogens and protect against oxidative stress. This study was undertaken to examine the impact of gene-smoking interactions on susceptibility to rheumatoid arthritis (RA).Caucasian patients with RA and matched control subjects (n = 549 each) were selected from the Nurses' Health Study. Genotyping of the patients' blood by TaqMan and BioTrove assays identified homozygous deletions at the M1 and T1 loci of GST (GSTM1-null and GSTT1-null, respectively) as well as alleles for GSTP1 (rs1695) and HMOX1 (rs2071746). In addition, the effect of gene-smoking interactions on the risk of all RA and RA serologic phenotypes was studied in separate logistic models that were adjusted for covariates. Multiplicative interactions were assessed by including a product term in a logistic model, and additive interactions were assessed using the attributable proportion (AP) due to interaction. For replication of the results, analyses revealing significant interactions were repeated in an independent case-control cohort from the Epidemiological Investigation of Rheumatoid Arthritis study.For the risk of all RA, multiplicative (P = 0.05) and additive (AP = 0.53, P = 0.0005) interactions between the GSTT1-null polymorphism and smoking and multiplicative interactions (P = 0.05) between HMOX1 and smoking were observed. For the risk of seropositive RA, multiplicative (P = 0.01) and additive (AP = 0.62, P < 0.0001) interactions between GSTT1-null and smoking and additive interactions (AP = 0.41, P = 0.03) between HMOX1 and smoking were observed. After correction for multiple comparisons, the additive interactions between GSTT1-null and smoking remained significant. The M1-null and P1 variants of GST did not show significant interactions, and no associations with seronegative RA were observed. In replication analyses, significant multiplicative interactions (P = 0.04) and additive interactions (AP = 0.32, P = 0.02) were observed between GSTT1-null and smoking in the risk of anti-citrullinated protein antibody-positive RA.Significant gene-environment interactions between the GSTT1-null polymorphism and heavy smoking were observed when assessing the risk of RA. Future studies are needed to assess the impact of these interactions on RA prediction.

Dataset Information

Urinary isothiocyanates; glutathione S-transferase M1, T1, and P1 polymorphisms; and risk of colorectal cancer: the Multiethnic Cohort Study.

Publications

Urinary isothiocyanates; glutathione S-transferase M1, T1, and P1 polymorphisms; and risk of colorectal cancer: the Multiethnic Cohort Study.

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