Genetic variant rs16430 6bp > 0bp at the microRNA‐binding site in TYMS and risk of sporadic breast cancer risk in non‐hispanic white women aged ≤55 years

Abstract

Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A > G, rs16430 6 bp > 0 bp, and rs1059394 C > T) in the predicted miRNA-binding sites of TYMS with risk of sporadic breast cancer in non-Hispanic white women aged ≤55. We found that carriers of the rs16430 0 bp variant allele had an increased risk of breast cancer [adjusted odd ratio (OR) = 1.37, 95% confidence interval (CI): 1.08–1.73; P = 0.010], compared with carriers of the 6 bp/6 bp genotype. This increased risk was more evident in older subjects (OR = 1.47, 95% CI = 1.06–2.03, P =0.022), never smokers (OR 1.67, 95% CI = 1.23–2.25, P < 0.001), never drinkers (OR = 1.44, 95% CI 1.01–2.05, P=0.043), and estrogen receptor-positive patients (OR=1.46, 95% CI=1.11–1.92, P=0.006), regardless of tumor stages. The results are consistent with the functional analyses of rs16430 as previously reported, which showed that the 0bp allele had a decrease in both luciferase activity by ~70% and mRNA levels by ~50% compared with the 6bp allele. Additionally, the rs16430 variant was predicted to influence the binding activity of miR-561 Taken together, these findings indicate that the TYMS rs16430 may contribute to the etiology of sporadic breast cancer in non-Hispanic white women aged ≤55 yr. Further validation in large population-based or cohort studies is needed.

3’UTR polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions

“…Nevertheless, this was the first study to evaluate the link between the risk of persistence of pre-neoplastic cervical lesions and the presence of genetic polymorphisms in enzymes that act on folate metabolism. Some authors have shown an association between the TS3'UTR polymorphism and esophageal, gastric, and breast cancers, although the results were controversial and varied with ethnicity [48][49][50][51][52]. However, studies on this polymorphism as a marker of cervical carcinogenesis have shown promising results, and further investigations are needed.…”

Genotype and allele frequencies of TYMS rs2790 A > G polymorphism in a Chinese paediatric population with acute lymphoblastic leukaemia

“…13,16,17 Some researchers explored the associations of genetic polymorphisms in TYMS with the risk for ALL development and clinical responses to MTX therapy. European populations also confirmed the interethnic differences in the distribution of the investigated polymorphism.…”

“…European populations also confirmed the interethnic differences in the distribution of the investigated polymorphism. 13,16,17 Some researchers explored the associations of genetic polymorphisms in TYMS with the risk for ALL development and clinical responses to MTX therapy. The protective role of the rs34743033 3R allele was reported in a population which consisted of 71 adult patients with ALL.…”

MicroRNAs Responsible for Inflammation in Obesity

“…MiR-1273, miR-190, miR-561, miR-151, miR-215, miR-196, and miR-328 are suggested to play a role in different types of cancer [68][69][70][71][72][73][74][75], whereas miR-3155A, miR-933, miR-4685, miR-640, and miR-4659 have not been associated to a specific function or disease yet. It has been stated that obesity is strongly associated with alterations in the physiological function of adipose tissue, resulting in insulin resistance, chronic inflammation, and changed secretion of adipokines.…”