TY - JOUR
T1 - 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 ≤55years
AU - Guan, Xiaoxiang
AU - Liu, Hongliang
AU - Ju, Jingfang
AU - Li, Yangkai
AU - Li, Peng
AU - Wang, Li E.
AU - Brewster, Abenaa M.
AU - Buchholz, Thomas A.
AU - Arun, Banu K.
AU - Wei, Qingyi
AU - Liu, Zhensheng
N1 - Publisher Copyright:
© 2013 Wiley Periodicals, Inc.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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 6bp>0bp, 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 0bp 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 6bp/6bp 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 ≤55yr. Further validation in large population-based or cohort studies is needed.
AB - 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 6bp>0bp, 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 0bp 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 6bp/6bp 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 ≤55yr. Further validation in large population-based or cohort studies is needed.
KW - Breast cancer
KW - Genetic susceptibility
KW - MiR-561
KW - MicroRNA
KW - Molecular epidemiology
KW - TYMS
UR - http://www.scopus.com/inward/record.url?scp=84924799382&partnerID=8YFLogxK
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U2 - 10.1002/mc.22097
DO - 10.1002/mc.22097
M3 - Article
C2 - 24166930
AN - SCOPUS:84924799382
SN - 0899-1987
VL - 54
SP - 281
EP - 290
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 4
ER -