title: Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women.
abstract: GWAS have identified variation in the FGFR2 locus as risk factors for breast cancer. Validation studies, however, have shown inconsistent results by ethnics and pathological characteristics. To further explore this inconsistency and investigate the associations of FGFR2 variants with breast cancer according to intrinsic subtype (Luminal-A, Luminal-B, ER-&PR-&HER2+, and triple negative) among Southern Han Chinese women, we genotyped rs1078806, rs1219648, rs2420946, rs2981579, and rs2981582 polymorphisms in 609 patients and 882 controls. Significant associations with breast cancer risk were observed for rs2420946, rs2981579, and rs2981582 with OR (95% CI) per risk allele of 1.19 (1.03-1.39), 1.24 (1.07-1.43), and 1.17 (1.01-1.36), respectively. In subtype specific analysis, above three SNPs were significantly associated with increased Luminal-A risk in a dose-dependent manner (P trend < 0.01); however, only rs2981579 was associated with Luminal-B, and none were linked to ER-&PR- subtypes (ER-&PR-&HER2+ and triple negative). Haplotype analyses also identified common haplotypes significantly associated with luminal-like subtypes (Luminal-A and Luminal-B), but not with ER-&PR- subtypes. Our results suggest that associations of FGFR2 SNPs with breast cancer were heterogeneous according to intrinsic subtype. Future studies stratifying patients by their intrinsic subtypes will provide new insights into the complex genetic mechanisms underlying breast cancer.
authors.affiliation: School of Biotechnology, Southern Medical University, Shatai Southern Road 1023, Baiyun District, Guangzhou, Guangdong 510515, China ; Institute of Pediatrics, Guangzhou Women and Children Medical Center, 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: 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: 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: 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: Obstetrics Outpatient Clinic, Guangzhou Women and Children Medical Center, Jinsui Road 9, Tianhe District, Guangzhou, Guangdong 510623, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
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: D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D012307:Risk Factors
chemical_list: C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2