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Journal of Cancer Research and Clinical Oncology

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01.08.2015 | Original Article – Cancer Research

Intronic and promoter polymorphisms of hMLH1/hMSH2 and colorectal cancer risk in Heilongjiang Province of China

verfasst von: Guangxiao Li, Fulan Hu, Fengshun Yuan, Jialong Fan, Zhifu Yu, Zhiwei Wu, Xiaojuan Zhao, Ye Li, Shuying Li, Jiesheng Rong, Binbin Cui, Xinshu Dong, Huiping Yuan, Yashuang Zhao

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 8/2015

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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.

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.

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 % (OR_adj = 0.69, 95 % CI 0.53–0.91, p < 0.01) and 33 % (OR_adj = 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).

Conclusions

Our findings suggested that intronic SNPs, gene–gene and gene–environment interactions in hMSH2 might be associated with susceptibility to CRC.

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Titel: Intronic and promoter polymorphisms of hMLH1/hMSH2 and colorectal cancer risk in Heilongjiang Province of China
verfasst von: Guangxiao Li
Fulan Hu
Fengshun Yuan
Jialong Fan
Zhifu Yu
Zhiwei Wu
Xiaojuan Zhao
Ye Li
Shuying Li
Jiesheng Rong
Binbin Cui
Xinshu Dong
Huiping Yuan
Yashuang Zhao
Publikationsdatum: 01.08.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 8/2015
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-014-1898-6

Springer Medizin

Intronic and promoter polymorphisms of hMLH1/hMSH2 and colorectal cancer risk in Heilongjiang Province of China