Association between polymorphisms in the thymidylate synthase gene and risk of breast cancer in a Mexican population

Abstract

ABSTRACT. Breast cancer (BC) is the leading cause of cancer-related deaths among women in Mexico. Two single-nucleotide polymorphisms (SNPs) in the thymidylate synthase (TS) gene, the 28-base pair (bp) 8750©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (4): 8749-8756 (2014) A. Quintero-Ramos et al. tandem repeat in the TS 5'-untranslated enhanced region (TSER) and the 6-bp insertion/deletion in the TS 3'-untranslated region (TS 3'-UTR), increase the rate of misincorporation of uridylate into DNA and may lead to chromosomal damage. We examined the association between these polymorphisms and BC risk in Mexican women according to menopause status. Mexican patients with initial BC diagnosis (N = 230) and 145 individuals from a reference general population group (RGP) were included. For statistical analysis, the BC group was divided into pre-and post-menopause groups (PRE and POST groups, respectively). We analyzed both TS polymorphisms (TSER and TS 3'-UTR) using polymerase chain reaction. Finetti analysis was used to evaluate interand intra-group differences. The results showed a high frequency for the 3R and ins6 alleles in the BC, RGP, PRE, and POST groups. No significant differences were observed for the TS and TSER genotype and allele frequency distributions between groups. We found that the TSER and TS 3'-UTR SNPs are not associated with BC risk in Mexican patients.

The polymorphisms of genes involved in DNA methylation in patients with malignancies from West Ukraine

“…Our results are very similar to those reported for the Spanish [27] and Mexican [28] women. The studies on other populations have found the significant associations between the TYMS gene TSER variations and breast cancer development [14].…”

Thymidylate synthase predicts poor response to pemetrexed chemotherapy in patients with advanced breast cancer

“…As a multitargeted antifolate, pemetrexed inhibits several de novo synthesis enzymes for purine and pyrimidine, including TYMS. Previous clinical and in vitro studies showed that cancer cell lines with TYMS expression showed poor sensitivity to cisplatin-and taxane-based chemotherapy regimens (24,25). Pemetrexed treatment in non-small cell lung cancer patients indicated that low TYMS mRNA expression was associated with increased ORR (26), and TYMS was an appropriate biomarker for pemetrexed chemotherapy response in non-small cell lung cancer (9,10,27).…”

Genomic Disparities in Breast Cancer among Latinas

“…Genes or pathways studied have included those related to hormone metabolism, hormone receptors, and hormone coactivators or supressors, 148,164–169 growth factors, 149,170–176 matrix metalloproteinases, 177,178 inflammation and energy balance, 158,179–184 metabolism of xenobiotic compounds and oxidative stress, 159,185–188 DNA repair, 160,161,163,189 and angiogenesis. 190 Results reported in these publications should be interpreted with caution, given that approximately 60% of the candidate gene analyses included in our report did not adjust for genetic ancestry, which is a known confounder in genetic association studies in admixed populations.…”