title: Associations of Genetic Variants at Nongenic Susceptibility Loci with Breast Cancer Risk and Heterogeneity by Tumor Subtype in Southern Han Chinese Women.
abstract: Current understanding of cancer genomes is mainly "gene centric." However, GWAS have identified some nongenic breast cancer susceptibility loci. Validation studies showed inconsistent results among different populations. To further explore this inconsistency and to investigate associations by intrinsic subtype (Luminal-A, Luminal-B, ER-&PR-&HER2+, and triple negative) among Southern Han Chinese women, we genotyped five nongenic polymorphisms (2q35: rs13387042, 5p12: rs981782 and rs4415084, and 8q24: rs1562430 and rs13281615) using MassARRAY IPLEX platform in 609 patients and 882 controls. Significant associations with breast cancer were observed for rs13387042 and rs4415084 with OR (95% CI) per-allele 1.29 (1.00-1.66) and 0.83 (0.71-0.97), respectively. In subtype specific analysis, rs13387042 (per-allele adjusted OR = 1.36, 95% CI = 1.00-1.87) and rs4415084 (per-allele adjusted OR = 0.82, 95% CI = 0.66-1.00) showed slightly significant association with Luminal-A subtype; however, only rs13387042 was associated with ER-&PR-&HER2+ tumors (per-allele adjusted OR = 1.55, 95% CI = 1.00-2.40), and none of them were linked to Luminal-B and triple negative subtype. Collectively, nongenic SNPs were heterogeneous according to the intrinsic subtype. Further studies with larger datasets along with intrinsic subtype categorization should explore and confirm the role of these variants in increasing breast cancer risk.
authors.affiliation: Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Jinsui Road 9, Tianhe District, Guangzhou, Guangdong 510623, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Liang
authors.affiliation: School of Biotechnology, Southern Medical University, Shatai Southern Road 1023, Baiyun District, Guangzhou, Guangdong 510515, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Biotechnology, Southern Medical University, Shatai Southern Road 1023, Baiyun District, Guangzhou, Guangdong 510515, China.
authors.forename: Xuexi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Breast Center Nanfang Hospital, Southern Medical University, Shatai Southern Road 1023, Baiyun District, Guangzhou, Guangdong 510515, China.
authors.forename: Lujia
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Biotechnology, Southern Medical University, Shatai Southern Road 1023, Baiyun District, Guangzhou, Guangdong 510515, China.
authors.forename: Anna
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Department of Primary Public Health, Guangzhou Center for Disease Control and Prevention, Qide Road 1, Baiyun District, Guangzhou, Guangdong 510440, China.
authors.forename: Minying
authors.initials: M
authors.lastname: Sun
authors.affiliation: Breast Center Nanfang Hospital, Southern Medical University, Shatai Southern Road 1023, Baiyun District, Guangzhou, Guangdong 510515, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Ye
authors.affiliation: School of Biotechnology, Southern Medical University, Shatai Southern Road 1023, Baiyun District, Guangzhou, Guangdong 510515, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D002681:China / Q000208:ethnology; D004198:Disease Susceptibility / Q000208:ethnology; D005260:Female; D056426:Genetic Loci; D006801:Humans; D011110:Polymorphism, Genetic