Assessing interactions between the associations of fibroblast growth factor receptor 2 common genetic variants and hormone receptor status with breast cancer risk

• Published in: Breast cancer research and treatment Vol. 137; no. 2; pp. 511 - 522
• Main Authors: Wang, Hong, Yang, Ziang, Zhang, Hongwei
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.01.2013; Springer; Springer Nature B.V
• Subjects: Angiogenesis; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Breast cancer; Breast Neoplasms - ethnology; Breast Neoplasms - genetics; Cancer research; Cancer therapies; Epidemiology; Estrogen; Ethnicity; European Continental Ancestry Group - genetics; Female; Fibroblast growth factors; Genes; Genetic Predisposition to Disease; Genetic research; Genomics; Gynecology. Andrology. Obstetrics; Health aspects; Hormones; Humans; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Meta-analysis; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Oncology; Polymorphism; Polymorphism, Single Nucleotide; Progesterone; Publication Bias; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Receptors, Estrogen - genetics; Risk Factors; Tumors; Breast; Estrogen receptor; Progesterone receptor; Cancer; Polymorphism; Meta-analysis; Breast disease; Genetic variability; Interaction; Genetic variant; Genotype; Breast cancer; Malignant tumor; Metaanalysis; Mammary gland diseases; Risk factor; Mammary gland; Fibroblast growth factor receptor 2; FGFR2; Hormonal receptor
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-012-2343-7

Fibroblast growth factor receptor 2 ( FGFR2 ) is a member of a receptor tyrosine kinase gene superfamily, involved in cell growth, invasiveness, motility, and angiogenesis, which has attracted considerable attention as a candidate gene for breast cancer (BC) since it was first identified through genome-wide association approach. In the past few years, the relationship between FGFR2 and BC has been reported in various ethnic groups; however, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 37 studies involving a total of 288,142 subjects for rs2981582, rs1219648, and rs2420946 polymorphism of the FGFR2 gene to evaluate the effect of FGFR2 on genetic susceptibility for BC. Overall, significantly increased BC risk was associated with these polymorphisms when all studies were pooled into the meta-analysis. In addition, our data indicate that FGFR2 is involved in BC susceptibility and confer its effect primarily in estrogen receptor-positive and progesterone receptor-positive tumors. When stratified by ethnicity, significantly increased risks were found in Caucasian and East Asian populations. However, no significant associations were detected among African descent populations. There was strong evidence of heterogeneity ( P  < 0.05), which largely disappeared after stratification by ethnicity. This meta-analysis demonstrated that FGFR2 polymorphism is a risk factor associated with increased BC susceptibility, but these associations vary in different ethnic populations.