Microsomal glutathione S-transferase gene polymorphisms and colorectal cancer risk in a Han Chinese population.
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.
Zhang
Hao
H
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
Liao
Ling-Hong
LH
Liu
Shuk-Ming
SM
Lau
Kwok-Wai
KW
Lai
Albert Kai-Cheong
AK
Zhang
Jin-Hui
JH
Wang
Qi
Q
Chen
Xiao-Qian
XQ
Wei
Wei
W
Liu
Hua
H
Cai
Jian-Hua
JH
Lung
Maria Li
ML
Tai
Susan S W
SS
Wu
Madeline
M
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*
D004247:DNA; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase