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Genetic polymorphisms and breast cancer risk: evidence from meta-analyses, pooled analyses, and genome-wide association studies

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Abstract

To address the association between variants and breast cancer, an increasing number of articles on genetic association studies, genome-wide association studies (GWASs), and related meta- and pooled analyses have been published. Such studies have prompted an updated assessment of the associations between gene variants and breast cancer risk. We searched PubMed, Medline, and Web of Science and retrieved a total of 87 meta- and pooled analyses, which addressed the associations between 145 gene variants and breast cancer. Analyses met the following criteria: (1) breast cancer was the outcome, (2) the articles were all published in English, and (3) in the recent published meta- and pooled analyses, the analyses with more subjects were selected. Among the 145 variants, 46 were significantly associated with breast cancer and the other 99 (in 62 genes) were not significantly associated with breast cancer. The summary ORs for the 46 significant associations (P < 0.05) were further assessed by the method of false-positive report probability (FPRP). Our results demonstrated that 10 associations were noteworthy: CASP8 (D302H), CHEK2 (*1100delC), CTLA4 (+49G>A), FGFR2 (rs2981582, rs1219648, and rs2420946), HRAS (rare alleles), IL1B (rs1143627), LSP1 (rs3817198), and MAP3K1 (rs889312). In addition, eight GWASs were identified, in which 25 loci were obtained (14 in nine genes, six near a gene or genes, and five intergenic loci). Of the 25 SNPs, 20 were noteworthy: C6orf97 (rs2046210 and rs3757318), FGFR2 (rs2981579, rs1219648, and rs2981582), LSP1 (rs909116), RNF146 (rs2180341), SLC4A7 (rs4973768), MRPS30 (rs7716600), TOX3 (rs3803662 and rs4784227), ZNF365 (rs10995190), rs889312, rs614367, rs13281615, rs13387042, rs11249433, rs1011970, rs614367, and rs1562430. In summary, in this review of genetic association studies, 31.7% of the gene-variant breast cancer associations were significant, and 21.7% of these significant associations were noteworthy. However, in GWASs, 80% of the significant associations were noteworthy.

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Acknowledgments

This study was supported by The “Eleventh Five-Year” Science and Technology Support Plan of the Ministry of Science and Technology of China (MSTC, 2009BA180B00) and a grant from the Natural Science Foundation of Zhejiang Province (NSFZJ, Y2090081). We thank Dr. Iain Bruce for valuable comments and English editing.

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Authors and Affiliations

  1. Department of Pathology, Zhejiang University School of Medicine, 388 Yuhangtang Road, Hangzhou, 310058, Zhejiang, People’s Republic of China

    Sihua Peng, Hongqiang Sheng & Maode Lai

  2. Department of Surgical Pathology, Affiliated Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China

    Bingjian Lü

  3. Department of Respiratory Diseases, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China

    Wenjing Ruan

  4. Department of Public Health, School of Medicine, Zhejiang University, Hangzhou, 310058, People’s Republic of China

    Yimin Zhu

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  1. Sihua Peng
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Correspondence to Maode Lai.

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Peng, S., Lü, B., Ruan, W. et al. Genetic polymorphisms and breast cancer risk: evidence from meta-analyses, pooled analyses, and genome-wide association studies. Breast Cancer Res Treat 127, 309–324 (2011). https://doi.org/10.1007/s10549-011-1459-5

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