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Prognostic significance of hMLH1/hMSH2 gene mutations and hMLH1 promoter methylation in sporadic colorectal cancer

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Abstract

No study in China has focused on the relationships between germline and somatic hMLH1/hMSH2 gene mutations, hMLH1 promoter methylation, and the prognosis of colorectal cancer (CRC), especially in sporadic CRC. Therefore, we carried out this study with 433 primary sporadic CRC patients to investigate the associations between germline and somatic hMLH1/hMSH2 gene mutations, hMLH1 promoter methylation, and the overall survival (OS) of CRC; to evaluate the effect of interaction between gene mutation and methylation on the risk of CRC prognosis. As a result, the 3-, 5-, and 7-year survival of the sporadic CRC patients was 67, 57, and 50.0 %, respectively. There were no significant associations observed between germline and somatic hMLH1/hMSH2 gene mutations after adjusted (HR = 1.37, 95 % CI 0.70–2.67, p = 0.35; HR = 1.31, 95 % CI 0.69–2.47, p = 0.42, respectively). When the analyses were stratified based on tumor stage, tumor location, and chemotherapy, no significant survival advantage of hMLH1/hMSH2 gene mutation was illustrated. In addition, no significant association between germline and somatic hMLH1 promoter methylation and OS of CRC was observed (HR = 1.46, 95 % CI 0.57–3.74, p = 0.43; HR = 0.70, 95 % CI 0.32–1.53, p = 0.37, respectively). In conclusion, the research did not find the significant association between germline and somatic hMLH1/hMSH2 gene mutations, hMLH1 promoter methylation, and sporadic CRC prognosis.

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Acknowledgments

Thanks for the Grants from the National Natural Science Foundation of China (Nos. 30671801, 30371243, and 30972538), Harbin Technological Innovation Talent Research Special Foundation (2011RFXXS045), and the Foundation for the Returned Scholars of Harbin (No. 2005AFLXJ017).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All the subjects included in the study have been approved by the Ethics Committee of Harbin Medical University.

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Authors and Affiliations

  1. Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, People’s Republic of China

    Yibaina Wang, Dandan Li, Xia Li, Lin Zhu, Yashuang Zhao & Fulan Hu

  2. Department of Medical Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin, People’s Republic of China

    Chong Teng

  3. Department of Colorectal Surgery, Cancer Hospital of Harbin Medical University, Harbin, People’s Republic of China

    Binbin Cui

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  1. Yibaina Wang
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  3. Xia Li
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  5. Lin Zhu
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Correspondence to Yashuang Zhao or Fulan Hu.

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Wang, Y., Li, D., Li, X. et al. Prognostic significance of hMLH1/hMSH2 gene mutations and hMLH1 promoter methylation in sporadic colorectal cancer. Med Oncol 31, 39 (2014). https://doi.org/10.1007/s12032-014-0039-z

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  • DOI: https://doi.org/10.1007/s12032-014-0039-z

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