Association of the single nucleotide polymorphisms in fgfr2 and tp53 genes with early onset breast cancer in Eastern and Southeastern Turkey

Early onset breast cancer rate has increased up to 25% in the developing countries. There are several studies that confirm that breast cancer cases of younger women have biological characteristics different from normal breast cancer cases and these patients should be studied separately. Recently, base changes that might have impact on breast cancer have been studied with GWAS but the number of studies on early onset breast cancer is very limited. The lack of necessary information about the younger patients prevents improvements about the diagnosis and treatment strategies targeting these patients. Polymorphisms within intron 2 of the FGFR2 gene rs1219648 and within exon 4 of the Tp53 gene rs1042522 have been associated with postmenopausal breast cancer patients in many populations but there is no research on the impact of rs1219648 and rs1042522 on early onset breast cancer in the Turkish population. This study focused on 75 patients for rs1219648 analyses and 96 patients for rs1042522 analyses under the age of 40, who applied to Dicle University, Faculty of Medicine, Department of Pathology between the years of 2010 and 2015, and the control group was comprised of 96 women under 40 years of age who did not have history and family history for any type of cancer. Individuals in the patient and control groups were selected from people born and raised in the Eastern and Southeastern Anatolia regions. Melting curve analysis was used for identification of amplicons via Light Cycler. Our results indicated that the rs1219648 polymorphism in the FGFR2 gene was statistically associated with the risk of early-onset breast cancer in Turkish population (p<0.05). G allele of the rs1219648 was strongly prominent in breast cancer patients (OR: 2.0098, 95% CI 1.3016-3.1032, p= 0.002). The rs1219648 was examined as a categorical variable related to the wild genotype (AA). The calculated OR was 5.2308 (95% CI 1.9391-14.1102), p = 0.001, for genotypes GG. When the GG genotype was considered as the reference for the analysis for rs1042522, the calculated OR value for the CG genotype of rs1042522 was found to be 0.4196 (95% CI 0.1941-0.9067), p = 0.027. These findings indicate that the CG genotype can be accounted for as a protective factor against early onset breast cancer in Turkish population. In our study, we have also examined the relation between these polymorphisms and clinicopathologic data of patients. As a result of statistical analysis, we determined that there was a significant association between ER status, histological grade, tumor size and rs1219648 polymorphism located in the second intron of the FGFR2 gene (p<0.05). According to the analyses of rs1042522 polymorphism within exon four of the Tp53 gene, it was determined that this polymorphism was only related to the PgR status (p<0.05). In order to verify our results, a large scale new studies about this subject in Turkish population are needed to be performed. Keywords: Early onset breast cancer, rs1219648, FGFR2 gene, Tp53 gene, rs1042522, Polymorphism