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Intronic and promoter polymorphisms of hMLH1/hMSH2 and colorectal cancer risk in Heilongjiang Province of China.
- Source :
-
Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2015 Aug; Vol. 141 (8), pp. 1393-404. Date of Electronic Publication: 2015 Jan 06. - Publication Year :
- 2015
-
Abstract
- Purpose: Given that mismatch repair (MMR) system plays an important role in recognizing and removing insertion/deletion mutations which occur during DNA replication, common variants associated with impaired MMR system may thus increase risk of colorectal cancer (CRC). Therefore, we aimed to demonstrate the associations between common variants in two MMR genes (hMLH1 and hMSH2) and CRC risk.<br />Methods: We genotyped 10 intronic/promoter single-nucleotide polymorphisms (SNPs) of hMLH1 and hMSH2 in 451 CRC patients and 630 controls. Associations between genotypes and CRC risk were estimated using odds ratios and 95 % confidence intervals. Gene-gene interactions, as well as gene-environment interactions on CRC risk were also investigated.<br />Results: We found that IVS15-214T>C and IVS11 + 107A>G of hMSH2 were significantly associated with CRC risk. In dominant model, variant carriers of the two SNPs could decrease risk of CRC by 31 % (ORadj = 0.69, 95 % CI 0.53-0.91, p < 0.01) and 33 % (ORadj = 0.67, 95 % CI 0.47-0.95, p = 0.02), respectively. In addition, IVS7-212T>A, IVS11+183A>G and IVS8+719T>C of hMSH2 were associated with the susceptibility to colon cancer rather than rectal cancer. ATTTGGGT and TCTTAGAC haplotypes were associated with 44 and 45 % decreased risk of CRC, respectively, while ATTTGAGT and TTTCAGAC haplotypes were associated with 1.37-fold and 2.49-fold increased risk of CRC, respectively. There was a significant three-way gene-gene interaction among hMSH2 IVS11+107A>G, IVS11+183A>G and IVS8+719T>C (p < 0.01). Significant gene-environment interactions were observed between hMSH2 IVS15-214T>C and IVS11+107A>G and cereals consumption (both with p < 0.01).<br />Conclusions: Our findings suggested that intronic SNPs, gene-gene and gene-environment interactions in hMSH2 might be associated with susceptibility to CRC.
- Subjects :
- Aged
Case-Control Studies
China epidemiology
Colorectal Neoplasms epidemiology
Epistasis, Genetic
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
MutL Protein Homolog 1
Polymorphism, Single Nucleotide
Risk Factors
Adaptor Proteins, Signal Transducing genetics
Colorectal Neoplasms genetics
Gene-Environment Interaction
Introns genetics
MutS Homolog 2 Protein genetics
Nuclear Proteins genetics
Promoter Regions, Genetic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1335
- Volume :
- 141
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of cancer research and clinical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 25560462
- Full Text :
- https://doi.org/10.1007/s00432-014-1898-6