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. Issue 4 (26th October 2013)

• Record Type: Journal Article
• Authors: Guan, Xiaoxiang; Liu, Hongliang; Ju, Jingfang; Li, Yangkai; Li, Peng; Wang, Li‐E; Brewster, Abenaa M.; Buchholz, Thomas A.; Arun, Banu K.; Wei, Qingyi; Liu, Zhensheng
• Is Part Of: Molecular carcinogenesis. Volume 54:Issue 4(2015:Apr.)
• Page Start: 281
• Page End: 290
• Publication Date: 2013-10-26
• Subjects: Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22097
• Languages: English
• ISSNs: 0899-1987

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="mc22097-sec-0001" sec-type="section"> <p>Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in <italic>TYMS</italic> 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 <italic>TYMS</italic> 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; <italic>P </italic>= 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, <italic>P</italic> = 0.022), never smokers (OR = 1.67, 95% CI = 1.23–2.25, <italic>P</italic> < 0.001), never drinkers (OR = 1.44, 95% CI = 1.01–2.05, <italic>P</italic> = 0.043), and estrogen receptor‐positive patients (OR = 1.46, 95% CI = 1.11–1.92, <italic>P</italic> = 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 <italic>miR‐561</italic>. Taken together, these findings indicate that the <italic>TYMS</italic> 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. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>