P21 Ser31Arg and FGFR2 rs2981582 Polymorphisms as Risk Factors for Early Onset of Breast Cancer in Yogyakarta, Indonesia

Abstract

Objectives: Breast cancer tend to be more progressive with poorer prognosis in younger patients than those at an older age. Single Nucleotide Polymorphisms (SNPs) of P53 Pro72Arg, MDM2 SNP309, P21 Ser31Arg, ER SNP594, HER2 Ile655Val, and FGFR2 rs2981582 have drawn attention as genetic factors associated with cancer risk. However, there were contradictory results involving different races and their association is still unknown in Indonesian populations. This study was performed to examine the proportion of these six genes polymorphisms and their associations with age of onset of breast cancer patients in Yogyakarta, Indonesia. Methods: Biorepository DNA from 199 patients registered at Dr. Sardjito Hospital Yogyakarta from 2006-2013 were tested for polymorphisms using the PCR-RFLP method. Samples were taken from two age groups; early-onset (<40 years) and late-onset of breast cancer (>55 years). Chisquare tests with odds ratio were used for data analysis. Results: The mean age of the early-onset group was 36±4.2 years, while the late-onset group was 62±6.9 years. AA genotype and A allele of P21 and TT genotypes and T allele of FGFR2 were significantly more frequent and were associated with an increased risk of early-onset of breast cancer (95%CI: 2.54 and 1.59; 2.63 and 1.64, respectively). Conclusions: Our study indicates that the A allele of P21 and the allele T of FGFR2 may be associated with an increased risk of early-onset of breast cancer in Yogyakarta, Indonesia. Further analysis is needed to confirm the findings.

FGFR families: biological functions and therapeutic interventions in tumors

“…224 Moreover, activating mutations in FGFR2 also induce Golgi fragmentation, loss of polarity, and directional migration. 225 In addition, gene polymorphisms of FGFR2, including rs2981582, [226][227][228][229] rs1219648, 230,231 rs35054928, and rs45631563, 232 have been found to be associated with susceptibility to breast cancer. In breast cancer, FGFR2 activates multiple pathways.…”

“…In addition, gene polymorphisms of FGFR2, including rs2981582, 226 , 227 , 228 , 229 rs1219648, 230 , 231 rs35054928, and rs45631563, 232 have been found to be associated with susceptibility to breast cancer. In breast cancer, FGFR2 activates multiple pathways.…”

FGFR2 genetic variants in women with breast cancer

“…The FGFR2 SNP that is most commonly associated with breast cancer in women of European ancestry, rs2981582 ( 17 ), was recently also associated with an increased risk of breast cancer in Saudi Arabian women ( 25 ), and with luminal A breast cancer in Han Chinese women ( 26 ) and Korean women ( 27 ). The expression of the minor allele was associated with early-onset breast cancer in Indonesian women ( 28 ). However, a study of women from Argentina and Uruguay did not find an association between rs2981582 and breast cancer, possibly because the populations of those countries include subpopulations of varied ethnicity (admixed populations) ( 29 ).…”