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Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry.

ABSTRACT: BACKGROUND:We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets. METHODS:Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets. FINDINGS:Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P?

SUBMITTER: Yang Y

PROVIDER: S-EPMC6838373 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry.

Yang Yaohua Y Shu Xiang X Shu Xiao-Ou XO Bolla Manjeet K MK Kweon Sun-Seog SS Cai Qiuyin Q Michailidou Kyriaki K Wang Qin Q Dennis Joe J Park Boyoung B Matsuo Keitaro K Kwong Ava A Park Sue Kyung SK Wu Anna H AH Teo Soo Hwang SH Iwasaki Motoki M Choi Ji-Yeob JY Li Jingmei J Hartman Mikael M Shen Chen-Yang CY Muir Kenneth K Lophatananon Artitaya A Li Bingshan B Wen Wanqing W Gao Yu-Tang YT Xiang Yong-Bing YB Aronson Kristan J KJ Spinell John J JJ Gago-Dominguez Manuela M John Esther M EM Kurian Allison W AW Chang-Claude Jenny J Chen Shou-Tung ST Dörk Thilo T Evans D Gareth R DGR Schmidt Marjanka K MK Shin Min-Ho MH Giles Graham G GG Milne Roger L RL Simard Jacques J Kubo Michiaki M Kraft Peter P Kang Daehee D Easton Douglas F DF Zheng Wei W Long Jirong J

EBioMedicine 20191016

<h4>Background</h4>We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets.<h4>Methods</h4>Of these 279 v ...[more]

PMID: 31629678

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Project description:ContextA genome-wide association study has identified three loci (five independent signals) that confer risk for polycystic ovary syndrome (PCOS) in Han Chinese women. Replication is necessary to determine whether the same variants confer risk for PCOS in women of European ancestry.ObjectiveThe objective of the study was to test whether these PCOS risk variants in Han Chinese women confer risk for PCOS in women of European ancestry.DesignThis was a case-control study.SettingThe study was conducted at deCODE Genetics in Iceland and two academic medical centers in the United States.PatientsCases were 376 Icelandic women and 565 and 203 women from Boston, MA, and Chicago, IL, respectively, all diagnosed with PCOS by the National Institutes of Health criteria. Controls were 16,947, 483, and 189 women not known to have PCOS from Iceland, Boston, and Chicago, respectively.InterventionThere were no interventions.Main outcomesMain outcomes were allele frequencies for seven variants in PCOS cases and controls.ResultsTwo strongly correlated Han Chinese PCOS risk variants on chromosome 9q33.3, rs10986105[C], and rs10818854[A], were replicated in samples of European ancestry with odds ratio of 1.68 (P = 0.00033) and odds ratio of 1.53 (P = 0.0019), respectively. Other risk variants at 2p16.3 (rs13405728), 2p21 (rs12468394, rs12478601, and rs13429458), and 9q33.3 (rs2479106), or variants correlated with them, did not associate with PCOS. The same allele of rs10986105 that increased the risk of PCOS also increased the risk of hyperandrogenism in women without PCOS from Iceland and demonstrated a stronger risk for PCOS defined by the National Institutes of Health criteria than the Rotterdam criteria.ConclusionsWe replicated one of the five Chinese PCOS association signals, represented by rs10986105 and rs10818854 on 9q33, in individuals of European ancestry. Examination of the subjects meeting at least one of the Rotterdam criteria for PCOS suggests that the variant may be involved in the hyperandrogenism and possibly the irregular menses of PCOS.

Dataset Information

Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry.

Publications

Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry.

Similar Datasets

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