Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center and.
Human Molecular Genetics (Impact Factor: 6.39). 03/2013; 22(12). DOI: 10.1093/hmg/ddt089
Source: PubMed


In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at P < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ∼10% of excess familial risk of breast cancer in Asian populations.

Download full-text


Available from: Jiajun Shi
  • Source
    • "The KOHBRA Study group performed various domestic and international collaborative studies to identify genetic variants associated with breast cancer risk through genome-wide association studies [42-44]. We are also participating in the International BRCA1/2 Carrier Cohort Study and the Consortium of Investigators of Modifiers of BRCA1/2 to identify epidemiologic factors and genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Most studies related to BRCA mutations have been performed in Western populations, and only a few small studies have been conducted in Korean populations. In 2007, the Korean Hereditary Breast Cancer (KOHBRA) Study was established to obtain evidence for the accurate risk assessment and management of hereditary breast and ovarian cancer (HBOC) in Korea. Between May 2007 and May 2010, the first phase of the KOHBRA Study was performed to estimate the prevalence of BRCA1/2 mutations among patients and their families at risk for HBOC. Between June 2010 and May 2013, the second phase of the KOHBRA Study was performed to identify the clinical characteristics and prognostic indicators of BRCA-related breast cancer and environmental and genetic modifiers of BRCA mutations and to develop a Korean BRCA risk calculator and nationwide genetic counseling network for HBOC. Herein, we review the results of the KOHBRA Study and describe the future perspectives of the study.
    Full-text · Article · Sep 2013 · Journal of Breast Cancer
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations. METHODS: We evaluated nine of those non-replication loci in East Asians in order to identify new risk variants for breast cancer in these regions. First, we analyzed single nucleotide polymorphisms (SNPs) 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 a 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 odds ratios (OR) 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% 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). CONCLUSIONS: 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.
    Full-text · Article · May 2013 · Cancer Epidemiology Biomarkers & Prevention
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A recent genome-wide association study (GWAS) has identified three new breast cancer susceptibility loci at 12p11, 12q24 and 21q21 in populations of European descent. However, because of the genetic heterogeneity, it is largely unknown for the role of these loci in the breast cancer susceptibility in the populations of non-European descent. Here, we genotyped three variants (rs10771399 at 12p11, rs1292011 at 12q24 and rs2823093 at 21q21) in an independent case-control study with a total of 1792 breast cancer cases and 1867 cancer-free controls in a Chinese population. We found that rs10771399 and rs1292011 were significantly associated with risk of breast cancer with per-allele odds ratios (ORs) of 0.85 (95% confidence interval (CI): 0.76-0.96; P = 0.010) and 0.84 (95% CI: 0.76-0.95; P = 4.50×10(-3)), respectively, which was consistent with those reported in populations of European descent. Similar effects were observed between ER/PR positive and negative breast cancer for both loci. However, we did not found significant association between rs2823093 and breast cancer risk (OR = 0.97, 95%CI = 0.76-1.24; P = 0.795). Our results indicate that genetic variants at 12p11 and 12q24 may also play an important role in breast cancer development in Chinese women.
    Preview · Article · Jun 2013 · PLoS ONE
Show more