J Breast Cancer.  2013 Dec;16(4):366-371. 10.4048/jbc.2013.16.4.366.

Case-Control Study on the Fibroblast Growth Factor Receptor 2 Gene Polymorphisms Associated with Breast Cancer in Chinese Han Women

• Liu CL
• Hu XP
• Guo WD
• Yang L
• Dang J
• Jiao HY

• KMID: 1976373
• DOI: http://doi.org/10.4048/jbc.2013.16.4.366

Abstract

PURPOSE
Genetic variation in fibroblast growth factor receptor 2 (FGFR2) is a newly described risk factor for breast cancer. This study aimed to evaluate the association of four single nucleotide polymorphisms (SNPs) in FGFR2 with breast cancer in Han Chinese women.
METHODS
Two hundred three women with breast cancer and 200 breast cancer-free age-matched controls were selected. Four SNPs (rs2981579, rs1219648, rs2420946, and rs2981582) and their haplotypes were analyzed to test for their association with breast cancer susceptibility. The presence of the four FGFR2 SNPs was determined by polymerase chain reaction-restriction fragment length polymorphism analysis.
RESULTS
A statistically significant difference was observed in the frequency of rs2981582 in the FGFR2 gene (p<0.05) between case and control groups. In subjects stratified by menopausal status, rs2981582 TT, rs2420946 AA, and rs1219648 CC were significantly associated with the risk of breast cancer in postmenopausal subjects, but no significant associations between these four SNPs and the risk of breast cancer were identified in premenopausal subjects. Further, there was no significant association between hormone receptor status (estrogen receptor and progesterone receptor) and breast cancer risk. Six common (> 3%) haplotypes were identified. Three of these haplotypes, CGTC (odds ratio [OR], 0.613; 95% confidence interval [CI], 0.457-0.82; p=0.001), TGTC (OR, 6.561; 95% CI, 2.064-20.854; p<0.001), and CATC (OR, 12.645; 95% CI, 1.742-91.799; p=0.001) were significantly associated with breast cancer risk.
CONCLUSION
Our findings indicated that the SNP rs2981582 and haplotypes CGTC, TGTC, and CATC in FGFR2 may be associated with an increased risk of breast cancer in Han Chinese women.

Keyword

Breast neoplasms; Single nucleotide polymorphisms; Type 2 fibroblast growth factor receptor

MeSH Terms

Asian Continental Ancestry Group*
Breast
Breast Neoplasms
Case-Control Studies*
Female
Fibroblast Growth Factors*
Fibroblasts*
Genetic Variation
Haplotypes
Humans
Polymorphism, Single Nucleotide
Progesterone
Receptor, Fibroblast Growth Factor, Type 2*
Receptors, Fibroblast Growth Factor*
Risk Factors
Fibroblast Growth Factors
Progesterone
Receptor, Fibroblast Growth Factor, Type 2
Receptors, Fibroblast Growth Factor

Figure

• 

  Figure 1 Results of polymerase chain reaction (PCR)-restriction fragment length Polymorphism (RFLP) and sequence analysis carried out for resolution of FGFR2 rs2981582, rs2420946, rs1219648 and rs2981579. (A) The amplification of PCR products for four FGFR2 SNPs. Lanes 1-2 (176 bp), lanes 3-5 (429 bp), lanes 6-8 (230 bp) and lanes 9-11 (437 bp), Lane M: 100-bp ladder marker. (B) The genotyping for rs2981582, rs2420946, rs1219648, and rs2981579 of FGFR2. Lanes 1-3 of rs2981582 genotype patterns, TT[176 base pairs (bp)], TC (176+154+22bp), CC (154+22 bp); Lanes 4-6 of rs2420946 genotype patterns, GG (321+108bp), AG (429+321+108 bp), AA (429bp); Lanes 7-10 of rs1219648 genotype patterns,TT (230 bp) (7-8), CC (211+19 bp), TC (230+211+19 bp); Lanes 11-17 of rs rs2981579 genotype patterns, TT (437 bp) (lanes 11, 15, 16), CC (350+87 bp) (lanes 12, 13, 14), TC (437+350+87 bp) (lane 17), and Lane M:100-bp ladder marker. (C) Results of DNA sequence analysis, Wild and Mutant allele of four SNPs are indicated with arrows, respectively.

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