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A functional −77T>C polymorphism in XRCC1 is associated with risk of breast cancer

  • Epidemiology
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Abstract

X-ray repair cross-complementing 1 (XRCC1) plays a critical role in base excision repair and genetic variations of XRCC1 may be associated with cancer susceptibility. We tested this hypothesis by examining the contribution of polymorphism in the regulatory region of XRCC1 −77T>C to risk of breast cancer in 995 patients and 1,004 controls. We found this polymorphism was associated with an increased risk of breast cancer, with an OR of 1.25 (95% CI, 1.00–1.56) for the −77TC genotype and 2.55 (95% CI, 1.11–5.86) for the −77CC genotype compared with the −77TT genotype. Haplotype analysis combining the −77T>C with three well-studied non-synonymous polymorphisms (Arg194Trp, Arg280His, and Arg399Gln) showed that only the −77C-containing haplotype was associated with the risk. Moreover, the C allele had more than 3-fold decreased luciferase expression compared with the T allele in breast cancer cell line MCF-7 (P < 0.001). A meta-analysis of seven publications with a total 2,888 cancer cases and 3,177 controls demonstrated that −77C was significantly associated with cancer risk, with an OR of 1.34 (95% CI, 1.18–1.51) for the TC genotype and 1.53 (95% CI, 1.14–2.07) for the CC genotype compared with the TT genotype. In conclusion, these findings indicated that XRCC1 −77T>C polymorphism may be a genetic determinant for developing breast cancer.

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Abbreviations

XRCC1 :

X-ray repair cross-complementing 1

BER:

Base excision repair

PCR-RFLP:

Polymerase chain reaction-based restriction fragment length polymorphism

UTR:

Untranslated region

LD:

Linkage disequilibrium

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Acknowledgments

We would like to express our gratitude to all the subjects who participated in the study. This study was supported by Program for New Century Excellent Talents in University NCET-10-0388 to X Miao.

Conflict of interest statement

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Li Liu, Li Liu, Rong Zhong, Yihua Xu, Jing Wu, Shengyu Duan, Rui Rui, Shaofa Nie & Xiaoping Miao

  2. Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Peng Yuan

  3. State Key Laboratory of Molecular Oncology and Department of Etiology& Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Chen Wu & Dongxin Lin

  4. Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Xiaomin Zhang, Huan Guo & Tangchun Wu

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  1. Li Liu
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  2. Peng Yuan
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  3. Li Liu
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Corresponding authors

Correspondence to Shaofa Nie or Xiaoping Miao.

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L. Liu and P. Yuan have contributed equally to this work.

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Liu, L., Yuan, P., Liu, L. et al. A functional −77T>C polymorphism in XRCC1 is associated with risk of breast cancer. Breast Cancer Res Treat 125, 479–487 (2011). https://doi.org/10.1007/s10549-010-0959-z

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