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Functional polymorphisms of ITGB1 are associated with clinical outcome of Chinese patients with resected colorectal cancer

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Abstract

Purpose

Integrin β1 (ITGB1) has been recognized to play a major role in tumor growth, invasion and metastasis. However, effects of single-nucleotide polymorphisms (SNPs) in ITGB1 gene on the prognosis of patients with colorectal cancer (CRC) have not been reported.

Methods

A total of 372 patients with resected colorectal adenocarcinoma were enrolled in our study. Three functional SNPs (rs2230395, rs1187075 and rs1187076) in ITGB1 were selected and genotyped using the Sequenom iPLEX genotyping system.

Results

We identified two SNPs (rs2230395 and rs1187075) in ITGB1 gene to be significantly associated with CRC overall survival (OS). Compared with the homozygous wild-type (AA) and heterozygous variant (AC), rs2230395 homozygous variant (CC) conferred a 1.55-fold (95 % CI 1.00–2.41, P = 0.049) increased risk of death. Similar result was obtained for homozygous variant (AA) in rs1187075 with a 1.62-fold (95 % CI 1.08–2.42, P = 0.020). In stratified analysis, this association in rs2230395 remained to be significant in patients receiving chemotherapy, but not in those without chemotherapy. We further evaluated the effects of chemotherapy on CRC survival in subgroups stratified by rs2230395 and rs1187075 genotypes. We found that chemotherapy resulted in a significantly better OS in patients with the homozygous wild-type (WW) or heterozygous variant (WV) genotype in both rs2230395 and rs1187075 when compared with patients with homozygous variant (VV) genotype.

Conclusions

Our data suggest that ITGB1 SNPs might be a prognostic biomarker for CRC patients, especially in those receiving chemotherapy. Our findings warrant validation in larger independent populations.

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Acknowledgments

This work was supported by Program for New Century Excellent Talents in University, National Natural Science Foundation (81201583), and International S&T Cooperation Program (2013DFA32110) of China.

Conflict of interest

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    Authors and Affiliations

    1. Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, 169 West Changle Street, Xi’an, 710032, China

      Feng Zhou & Xianli He

    2. Department of General Surgery, Huaihai Hospital, Xuzhou Medical College, Xuzhou, 221004, China

      Feng Zhou & Zhaohui Zhang

    3. State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 West Changle Street, Xi’an, 710032, China

      Xiaojun Huang, Yibing Chen & Jinliang Xing

    4. Xijing Hospital of Digestive Disease, Fourth Military Medical University, Xi’an, 710032, China

      Xiaonan Liu

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    1. Feng Zhou
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    Correspondence to Jinliang Xing or Xianli He.

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    Feng Zhou and Xiaojun Huang have contributed to this work equally.

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    Zhou, F., Huang, X., Zhang, Z. et al. Functional polymorphisms of ITGB1 are associated with clinical outcome of Chinese patients with resected colorectal cancer. Cancer Chemother Pharmacol 75, 1207–1215 (2015). https://doi.org/10.1007/s00280-015-2745-4

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