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Association between MutL homolog 1 polymorphisms and the risk of colorectal cancer: a meta-analysis

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

As one of the most essential components of mismatch repair system, MutL homolog 1 (MLH1) plays an increasingly implicated role in initiation and promotion of colorectal carcinogenesis, with germ-line mutations in different loci. However, whether a single genetic variant in MLH1 could predict the risk of cancer was still under doubt and recent studies yielded inconsistent results. Therefore, this meta-analysis aimed at investigating the association between MLH1 single-nucleotide polymorphisms (SNPs) and colorectal cancer (CRC) risks.

Methods

A systematic literature search of PubMed, MEDLINE, Web of Science and BIOSIS databases was performed to obtain all available SNPs and studies. We focused on three SNPs (rs1800734, rs1799977 and rs63750448) with the most included studies and conducted overall and subgroup analyses after data extraction.

Results

A total of 37,347, 29,114 and 2722 patients in case and control groups were meta-analyzed in four genetic models (AA vs. BB, AB vs. BB, AA+AB vs. BB and AA vs. BB+AB) for each SNP. The overall results suggested that the mutation in rs63750447 predicted a higher CRC risk (AB vs. BB: OR 2.283, 95 % CI 1.612–3.232, P = 0.000; AA+AB vs. BB: OR 2.291, 95 % CI 1.618–3.244, P = 0.000), while rs1800734 and rs1799977 were not associated with CRC risks. Subgroup analysis according to study area, quality score and genotyping technique revealed the similar results.

Conclusions

As the first meta-analysis reporting the association between rs63750448 and CRC risk, the A allele substitution might be a risk factor for CRC. Additionally, there was no persuasive evidence showing that SNPs of rs1800734 and rs1799977 were related to CRC susceptibility.

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Acknowledgments

This work was partly supported by grants from National Natural Science Foundation of China (Nos. 81272455, 81472664) and Zhejiang Provincial Natural Science Foundation of China (No. R2100071).

Conflict of interest

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    Authors and Affiliations

    1. The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Hangzhou, Zhejiang, China

      Haiyan Chen, Yeting Hu, Qian Xiao, Dikai Bei, Xiangfeng Shen & Kefeng Ding

    2. Department of Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

      Haiyan Chen, Yeting Hu, Qian Xiao, Dikai Bei, Xiangfeng Shen & Kefeng Ding

    3. Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China

      Zhujing Shen

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    Correspondence to Kefeng Ding.

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    Haiyan Chen and Zhujing Shen contributed equally to this work.

    Electronic supplementary material

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    FigS1

    ORs for the relation of MLH1 rs1800734 polymorphism and CRC risk with four genetic models (A, B, C and D). No statistical difference was observed (TIFF 4685 kb)

    FigS2

    ORs for the relation of MLH1 rs1799977 polymorphism and CRC risk with four genetic models (A, B, C and D). No statistical difference was observed (TIFF 5831 kb)

    FigS3

    Begg’s funnel plot for MLH1 rs1800734 polymorphism and CRC risk with four genetic models (A, B, C and D) (TIFF 14789 kb)

    FigS4

    Begg’s funnel plot for MLH1 rs1799977 polymorphism and CRC risk with four genetic models (A, B, C and D) (TIFF 10466 kb)

    FigS5

    Begg’s funnel plot for MLH1 63750447 polymorphism and CRC risk with AB VS BB and AA+AB VS BB genetic models (A and B, respectively). They suggested low risk of publication bias (TIFF 5160 kb)

    Supplementary material 6 (DOCX 103 kb)

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    Chen, H., Shen, Z., Hu, Y. et al. Association between MutL homolog 1 polymorphisms and the risk of colorectal cancer: a meta-analysis. J Cancer Res Clin Oncol 141, 2147–2158 (2015). https://doi.org/10.1007/s00432-015-1976-4

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    • DOI: https://doi.org/10.1007/s00432-015-1976-4

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