GSTT2 promoter polymorphisms and colorectal cancer risk.
BACKGROUND
Glutathione S-transferases are a group of enzymes that participate in detoxification and defense mechanisms against toxic carcinogens and other compounds. These enzymes play an important role in human carcinogenesis. In the present study, we sought to determine whether GSTT2 promoter single nucleotide polymorphisms (SNPs) are associated with colorectal cancer risk.


METHODS
A total of 436 colorectal cancer patients and 568 healthy controls were genotyped for three GSTT2 promoter SNPs (-537G>A, -277T>C and -158G>A), using real-time TaqMan assay and direct sequencing. An electrophoretic mobility shift assay (EMSA) was performed to determine the effects of polymorphisms on protein binding to the GSTT2 promoter.


RESULTS
The -537A allele (-537G/A or A/A) was significantly associated with colorectal cancer risk (OR = 1.373, p = 0.025), while the -158A allele (-158G/A or A/A) was involved in protection against colorectal cancer (OR = 0.539, p = 0.032). Haplotype 2 (-537A, -277T, -158G) was significantly associated with colorectal cancer risk (OR = 1.386, p = 0.021), while haplotype 4 (-537G, -277C, -158A) protected against colorectal cancer (OR = 0.539, p = 0.032). EMSA data revealed lower promoter binding activity in the -537A allele than its -537G counterpart.


CONCLUSIONS
Our results collectively suggest that SNPs and haplotypes of the GSTT2 promoter region are associated with colorectal cancer risk in the Korean population.
Jang
Sang-Geun
SG
Laboratory of Cell Biology, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, Korea. jangsg@gmail.com <jangsg@gmail.com>
Kim
Il-Jin
IJ
Kang
Hio Chung
HC
Park
Hye-Won
HW
Ahn
Sun-A
SA
Yoon
Hyun-Ju
HJ
Kim
Kun
K
Shin
Hai-Rim
HR
Lee
Jin Soo
JS
Park
Jae-Gahb
JG
D015179:Colorectal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
C491107:GSTT2 protein, human; D005982:Glutathione Transferase