Microsomal glutathione S-transferase gene polymorphisms and colorectal cancer risk in a Han Chinese population.

BACKGROUND AND AIMS: Glutathione S-transferases (GSTs) are phase II detoxification enzymes. Human GSTs have been classified into cytosolic, mitochondrial, and microsomal families. Several studies reported the association of colorectal cancer (CRC) risk with the genetic polymorphisms of cytosolic GSTs. The microsomal GSTs are structurally distinct but functionally similar to cytosolic GSTs; their association with CRC has not been reported. In this report, we summarized the result of a case-control study aimed at investigating the association of MGST1 gene locus polymorphisms with CRC risk among Han Chinese. PATIENT/METHODS: Three hundred and seventy-two healthy controls and 238 sporadic CRC patients participated in this study. DNA resequencing was conducted for the 3.4 kb genomic DNA region containing the promoter, exons, exon-intron junctions, and the 5' and 3' untranslated regions. RESULTS: We detected 13 single nucleotide polymorphisms (SNPs) including four novel SNPs not reported in database/literature. The gene shows a much higher nucleotide diversity than most human genes. The linkage and recombination analysis revealed 24 common haplotypes (13% > or = freq > or = 1%) and identified extensive intragenic recombination throughout the MGST1 locus (R = 81.8). Significant CRC association (P < or = 0.005) was not detected for each individual SNP. However, SNPs 102G>A and 16416G>A reached a marginal level of statistical significance with P values of 0.016 and 0.078, respectively. A combined genotype analysis detected a statistically significant CRC association for individuals carrying 102G>A/16416G>A (GG/GG) genotype (adjusted OR, 1.682; 95% confidence interval (CI), 1.177-2.404; P = 0.004). Consistent with the results of genotype analysis, the GG haplotype (102G>A/16416G>A) with two risk alleles was associated with a significantly higher CRC risk comparing with the haplotypes with one or no risk allele (adjusted OR 1.744; 95% CI 1.309-2.322; P = 0.0001). CONCLUSION: The results suggest that MGST1 polymorphisms may contribute to CRC risk among Han Chinese.

The association of CYP2C9 gene polymorphisms with colorectal carcinoma in Han Chinese.

BACKGROUND: Cytochrome P450 (CYP) 2C9 is an important enzyme involved in xenobiotics metabolism. This study investigated the association of CYP2C9 gene coding region polymorphisms with colorectal cancer (CRC) in Chinese Han population. METHODS: Four hundred and eighty-three healthy controls and 286 sporadic CRC patients participated in this study. Direct sequencing was used to identify the sequence polymorphisms. RESULTS: We detected the significant association of 2 coding region SNPs, rs1057910 and rs1057911, of CYP2C9 with the risk of developing sporadic CRC for Han Chinese. These 2 SNPs showed a strong linkage disequilibrium (LD) (r(2)=0.97, D'=0.985). Significantly different minor allele frequencies were found for SNPs rs1057910 and rs1057911 between the cases (7% and 7.2%, respectively) and controls (3% and 2.9%, respectively) with adjusted P=0.0004 and 0.0002, respectively. Individuals heterozygous for rs1057910A/C or rs1057911A/T showed 2.589-fold (95% CI: 1.549-4.330) or 2.770-fold (95% CI 1.653-4.643) increased risk of developing sporadic CRC. We did not detect any homozygote minor allele carrier for either rs1057910 or rs1057911 in our study population. The CRC association appeared to be more evident for individuals over age 50 y, for men, and for rectum cancer site. CONCLUSION: There is an association of CYP2C9 coding region polymorphisms with the risk of developing CRC in Han Chinese after genotyping cases and controls recruited from different locations in China.