Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1

Abstract

In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified three novel genetic loci associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene, P = 8.82 × 10−9), rs10474352 at 5q14.3 (near the ARRDC3 gene, P = 1.67 × 10−9), and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene, P = 4.25 × 10−8). These associations were replicated in European-ancestry populations including 16,003 cases and 41,335 controls (P = 0.030, 0.004, and 0.010, respectively). Data from the ENCODE project suggest that variants rs4951011 and rs10474352 may be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.

Modifiers of breast and ovarian cancer risks for BRCA1 and BRCA2 mutation carriers

“…Genotypes at many millions of common variants across the genome can be genotyped or imputed with high accuracy using largescale genotyping arrays, using reference panels from the 1000 Genomes Project (Auton et al 2015). This approach has been applied with great success in cancer epidemiology in the general population, with GWAS having identified more than 100 common susceptibility variants for breast cancer , Hunter et al 2007, Stacey et al 2007, Ahmed et al 2009, Thomas et al 2009, Antoniou et al 2010b, Turnbull et al 2010, Cai et al 2011, Fletcher et al 2011, Ghoussaini et al 2012, Hein et al 2012, Long et al 2012, Siddiq et al 2012, Bojesen et al 2013, French et al 2013, Garcia-Closas et al 2013, Gaudet et al 2013, Meyer et al 2013, Cai et al 2014, Milne et al 2014a, Orr et al 2015, Couch et al 2016, Dunning et al 2016, Lawrenson et al 2016, Zheng et al 2009) and 22 for ovarian cancer (Song et al 2009, Bolton et al 2010, Goode et al 2010, Bojesen et al 2013, Permuth-Wey et al 2013, Pharoah et al 2013, Kuchenbaecker et al 2015.…”

Heterozygosity Ratio, a Robust Global Genomic Measure of Autozygosity and Its Association with Height and Disease Risk

“…In PLINK, we quality controlled the BioVU data set for gender mismatches, relatedness, HWE, heterozygosity rate, and Mendelian error as stated in our protocol (Guo et al 2014a). In addition to BioVU Exome chip data, a second Exome chip data set of 10,906 (case N = 5852, control N = 5054) Chinese subjects from the Shanghai Breast Cancer Genetic Study (SBCGS) (Cai et al 2014) was used to test the association between heterozygosity ratio and height.…”

Variants in 6q25.1 Are Associated with Mammographic Density in Malaysian Chinese Women

“…We assessed the association of mammographic densities and genetic loci that have been known to be associated with one or more of these variables: mammographic density or breast size or both, in women of European ancestry and breast cancer risk in Asian women (6,11,17,18,(20)(21)(22)25). We also investigated the association of one SNP in PPARg that was found to be associated with mammographic density in Singaporean Chinese women (15).…”

“…A total of 56 publications were identified, and full versions of 4 publications were retrieved, from which we selected 20 genome-wide significant SNPs from four publications (18)(19)(20)(21) for genotyping. Four SNPs identified as breast cancer susceptibility loci in a then unpublished GWAS from the Asian Breast Cancer Consortium were also included for genotyping (22).…”