title: Microsomal glutathione S-transferase gene polymorphisms and colorectal cancer risk in a Han Chinese population.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  The results suggest that MGST1 polymorphisms may contribute to CRC risk among Han Chinese.
authors.affiliation: Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, People's Republic of China. bollh@ust.hk
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Ling-Hong
authors.initials: LH
authors.lastname: Liao
authors.forename: Shuk-Ming
authors.initials: SM
authors.lastname: Liu
authors.forename: Kwok-Wai
authors.initials: KW
authors.lastname: Lau
authors.forename: Albert Kai-Cheong
authors.initials: AK
authors.lastname: Lai
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Cai
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
authors.forename: Susan S W
authors.initials: SS
authors.lastname: Tai
authors.forename: Madeline
authors.initials: M
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D004247:DNA; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D004247:DNA; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase