Genetic Polymorphisms Of The2ed Intron Of Fibroblast Growth Factor Receptor2Associated With Breast Cancer Susceptibility In Han Race Of Hubei Province

Breast cancer, the most common malignant tumor in the world, is number one of female cancers in western countries. In our country, breast cancer is the top two in women cancers. About1.2million women suffer from breast cancer, and half million women dies of breast cancer each year in the world. The incidence rate of breast cancer has increased gradually in recent years. Many factors, such as genetic factors, hormone factors and benign mammary gland disease, are involved in the development of breast cancers. With the deep study of molecular biology, people have found some genes (eg.BP1, BRCA1, FGFR2) and SNP sites related to breast cancer. At present, molecular mechanism between the genes and the formation of breast cancer pathogenesis is still unclear. In this study, we investigated seven SNP sites of FGFR2related to breast cancer, and tried to found the relationship between seven SNPs and breast cancer through case-control analysis.636blood samples of breast cancer patients and771samples of healthy people as control were collected. We genotyped7SNPs of FGFR2via PCR amplification and direct sequencing. The distribution of SNP genotype and allele frequency were calculated using the direct counting method, then tested whether it fit Hardy-Weinberg balance by Goodness-of-fit Chi-square test. The OR (odds ratio) value between the genotype and allele of each SNP site with breast cancer risk was calculated under the condition in which all samples for each site met H-W equilibrium. Distributional difference of the haplotype of susceptibility SNPs between the patient group and the control group were assessed by SHEsis software.The results of this study indicate that the genotype and allele frequency distributions of the rs2981578are statistically different between patient and control groups (p<0.05), implying that the rs2981578site perhaps is a susceptibility loci of breast cancer. The distribution of genotype frequency of the rs3750817site also is statistically different between the patient group and the control group (p<0.05), and the genotype "C/T"(OR:1.63(1.22-2.17)) for this SNP is related to high risk of breast cancer, while the genotype "T/T"(OR:0.65(0.45-0.93)) appears to be related to low risk of breast cancer. Other SNP sites appear to be not relative with the development of breast cancer. There are four kinds of haplotypes in two SNP sites (rs2981578, rs3750817) which is located in the same linkage disequilibrium region. Two (rs2981578G-rs3750817C and rs2981578A-rs3750817T) of four haplotypes show significant differences between patient and control groups (p<0.05). The haPlotype rs2981578G-rs3750817C(OR:1.279(1.010-1.620)) is related to high risk of breast cancer.In conclusion, the SNP sites rs3750817and rs2981578in FGFR2gene are the susceptibility loci of breast cancer in Han people of Hubei province. Two SNP sites we found can perhaps be used as molecular markers to screen high-risk groups.