Polymorphisms in Second Intron of the FGFR2 Gene Are Associated with the Risk of Early-Onset Breast Cancer in Chinese Han Women

Polymorphisms in Second Intron of the FGFR2 Gene Are Associated with the Risk of Early-Onset Breast Cancer in Chinese Han Women

FANGMENG FU,^1,2 CHUAN WANG,¹ MENG HUANG,³ CHUANGUI SONG,¹ SHUNGUO LIN¹ and HEGUANG HUANG¹

¹Department of General Surgery, Affiliated Union Hospital of Fujian Medical University, Fuzhou, P.R. China
²Union Clinical School, Fujian Medical University, Fuzhou, P.R. China
³Fujian Center for Disease Control and Prevention, Fuzhou, P.R. China

Fibroblast growth factor receptor 2 (FGFR2) plays an important role in tumor cell growth, invasiveness, motility, and angiogenesis. Several single-nucleotide polymorphisms (SNPs) in the second intron of the FGFR2 gene are associated with the risk of breast cancer. In this study, we determined whether these SNPs of the FGFR2 gene are associated with early onset of non-familial breast cancer in a Chinese Han population. Recruited were 118 female breast cancer patients who were less than or equal to 35 years of age and without a family history of breast cancer, and 104 age-matched healthy controls. Six SNPs of the second intron of the FGFR2 gene, including rs2981428C/A (i.e., a change at this particular site from nucleotide C to A), rs11200014G/A, rs2981579C/T, rs1219648A/G, rs2420946C/T, and rs2981582C/T, were detected using matrix-assisted laser desorption/ionization mass spectrometry. The data showed that the homozygotes at each minor allele, rs11200014 (AA), rs1219648 (GG), rs2420946 (TT), and rs2981582 (TT), were significantly associated with an increased risk of early-onset non-familial breast cancer. The haplotype containing rs11200014A, rs1219648G, rs2420946T and rs2981582T also exhibited a significantly higher distribution in patients compared to controls (OR = 1.784, 95% CI = 1.161-2.744). In stratified analyses, each of the above four SNPs conferred a signicantly greater risk of estrogen receptor-positive breast cancer, compared to estrogen receptor-negative breast cancer that is more resistant to treatment. Our data demonstrate that these four SNPs of the FGFR2 gene are associated with the risk of breast cancer at a young age in Chinese Han women.

keywords —— early-onset breast cancer; cancer susceptibility; Chinese Han; fibroblast growth factor receptor 2; single-nucleotide polymorphism

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Tohoku J. Exp. Med., 2012, 226, 221-229

Correspondence: Heguang Huang, Department of General Surgery, Affiliated Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou 350001, P.R. China.

e-mail: hhuang2@yahoo.cn