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Association between co-inhibitory molecule gene tagging single nucleotide polymorphisms and the risk of colorectal cancer in Chinese

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

Abstract

Purpose

T lymphocyte immune responses are controlled by both co-stimulatory and co-inhibitory signaling through T cell co-receptors. Cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death 1 (PD-1) and B and T lymphocyte attenuator (BTLA) are all co-inhibitory molecules that negatively regulate the activation of T cells. In this study, we investigated the relationship between ten tagging SNPs in three co-inhibitory molecule genes and colorectal cancer (CRC).

Methods

We conducted a hospital-based case–control study consisting of 601 cases with CRC and 627 CRC-free individuals from the Heilongjiang Province of China.

Results

The rs7421861 CT genotype was significantly associated with the risk of colorectal cancer compared to the wild-type TT genotype (adjusted OR 1.314, 95 % CI 1.012–1.706, P = 0.041). The rs2705535 TT genotype was associated with the risk of rectal cancer [OR 1.819 (1.093–3.027), P = 0.021]. There was statistical interaction between the PD-1/rs2227982 (CT + TT) genotypes and high seafood intake (>once/week), as well as the CTLA-4/rs231777 variant and high pungent food intake (>3 times/week). The AG + AA genotypes of CTLA-4/rs3087243 statistically and antagonistically interacted with soybeans, pork and alcohol intake and were associated with CRC risk. Analogously, BTLA/rs1844089 interacted with pork intake, PD-1/rs7421861 with beef and lamb consumption and PD-1/rs6710479 with barbecue consumption. Haplotype G-C-G-A-T-T-A was significantly associated with CRC risk (OR 1.221 P = 0.034).

Conclusions

These data indicate potential associations between BTLA and PD-1 polymorphisms and CRC susceptibility. Additionally, the three co-inhibitory molecule gene SNPs have environmental interactions associated with CRC risk.

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Acknowledgments

This work was supported by grants from Natural Science Foundation of China (Grant No. 30972539) and Specialized Research Fund for the Technical Innovation Talented Person of Harbin (Grant No. 2011RFXXS045).

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Authors and Affiliations

  1. Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China

    Jie Ge, Lin Zhu, Guangxiao Li, Ye Li, Shuying Li, Zhiwei Wu & Yashuang Zhao

  2. Department of General Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China

    Junde Zhou & Qiang Chi

  3. Department of Orthopedics Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China

    Jiesheng Rong

  4. Department of Ophthalmology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China

    Huiping Yuan

  5. Department of Clinical Laboratory, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China

    Yanhong Liu

  6. Department of General Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China

    Daxun Piao

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

    Binbin Cui

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  1. Jie Ge
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  2. Lin Zhu
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  3. Junde Zhou
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  4. Guangxiao Li
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  5. Ye Li
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  10. Yanhong Liu
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Correspondence to Yashuang Zhao or Binbin Cui.

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Ge, J., Zhu, L., Zhou, J. et al. Association between co-inhibitory molecule gene tagging single nucleotide polymorphisms and the risk of colorectal cancer in Chinese. J Cancer Res Clin Oncol 141, 1533–1544 (2015). https://doi.org/10.1007/s00432-015-1915-4

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  • DOI: https://doi.org/10.1007/s00432-015-1915-4

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