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New breast cancer risk variant discovered at 10q25 in East Asian women.

ABSTRACT: BACKGROUND:Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study (GWAS) conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations. METHODS:We evaluated nine of those nonreplication loci in East Asians to identify new risk variants for breast cancer in these regions. First, we analyzed single-nucleotide polymorphisms (SNP) in these regions using data from two GWAS conducted among Chinese and Korean women, including 5,083 cases and 4,376 controls (stage 1). In each region, we selected an SNP showing the strongest association with breast cancer risk for replication in an independent set of 7,294 cases and 9,404 controls of East Asian descents (stage 2). Logistic regression models were used to calculate adjusted ORs and 95% confidence intervals (CI) as a measure of the association of breast cancer risk and genetic variants. RESULTS:Two SNPs were replicated in stage 2 at P < 0.05: rs1419026 at 6q14 [per allele OR, 1.07; 95% confidence interval (CI), 1.03-1.12; P = 3.0 × 10(-4)] and rs941827 at 10q25 (OR, 0.92, 95% CI, 0.89-0.96; P = 5.3 × 10(-5)). The association with rs941827 remained highly statistically significant after adjusting for the risk variant identified initially in women of European ancestry (OR, 0.88; 95% CI, 0.82-0.97; P = 5.3 × 10(-5)). CONCLUSION:We identified a new breast cancer risk variant at 10q25 in East Asian women. IMPACT:Results from this study improve the understanding of the genetic basis for breast cancer.

SUBMITTER: Shi J

PROVIDER: S-EPMC3720126 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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New breast cancer risk variant discovered at 10q25 in East Asian women.

Shi Jiajun J Sung Hyuna H Zhang Ben B Lu Wei W Choi Ji-Yeob JY Xiang Yong-Bing YB Kim Mi Kyung MK Iwasaki Motoki M Long Jirong J Ji Bu-Tian BT Park Sue K SK Zheng Ying Y Tsugane Shoichiro S Yoo Keun-Young KY Wang Wenjing W Noh Dong-Young DY Han Wonshik W Kim Sung-Won SW Lee Min Hyuk MH Lee Jong Won JW Lee Jong-Young JY Shen Chen-Yang CY Matsuo Keitaro K Ahn Sei-Hyun SH Gao Yu-Tang YT Shu Xiao Ou XO Cai Qiuyin Q Kang Daehee D Zheng Wei W

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20130515 7

<h4>Background</h4>Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study (GWAS) conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations.<h4>Methods</h4>We evaluated nine of those nonreplication loci in East Asians to identify new risk variants for breast cancer in these regions. First, we analyzed single-nucleotide polymorphisms (SNP) in these regions using data from two ...[more]

PMID: 23677579

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Project description:BackgroundThe Breast Cancer Risk Assessment Tool (BCRAT) of the National Cancer Institute is widely used for estimating absolute risk of invasive breast cancer. However, the absolute risk estimates for Asian and Pacific Islander American (APA) women are based on data from white women. We developed a model for projecting absolute invasive breast cancer risk in APA women and compared its projections to those from BCRAT.MethodsData from 589 women with breast cancer (case patients) and 952 women without breast cancer (control subjects) in the Asian American Breast Cancer Study were used to compute relative and attributable risks based on the age at menarche, number of affected mothers, sisters, and daughters, and number of previous benign biopsies. Absolute risks were obtained by combining this information with ethnicity-specific data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program and with US ethnicity-specific mortality data to create the Asian American Breast Cancer Study model (AABCS model). Independent data from APA women in the Women's Health Initiative (WHI) were used to check the calibration and discriminatory accuracy of the AABCS model.ResultsThe AABCS model estimated absolute risk separately for Chinese, Japanese, Filipino, Hawaiian, Other Pacific Islander, and Other Asian women. Relative and attributable risks for APA women were comparable to those in BCRAT, but the AABCS model usually estimated lower-risk projections than BCRAT in Chinese and Filipino, but not in Hawaiian women, and not in every age and ethnic subgroup. The AABCS model underestimated absolute risk by 17% (95% confidence interval = 1% to 38%) in independent data from WHI, but APA women in the WHI had incidence rates approximately 18% higher than those estimated from the SEER program.ConclusionsThe AABCS model was calibrated to ethnicity-specific incidence rates from the SEER program for projecting absolute invasive breast cancer risk and is preferable to BCRAT for counseling APA women.

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New breast cancer risk variant discovered at 10q25 in East Asian women.

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New breast cancer risk variant discovered at 10q25 in East Asian women.

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