Dataset Information

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 0 bp 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.

SUBMITTER: Guan X

PROVIDER: S-EPMC4464775 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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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.

Guan Xiaoxiang X Liu Hongliang H Ju Jingfang J Li Yangkai Y Li Peng P Wang Li-E LE Brewster Abenaa M AM Buchholz Thomas A TA Arun Banu K BK Wei Qingyi Q Liu Zhensheng Z

Molecular carcinogenesis 20131026 4

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 ha ...[more]

PMID: 24166930

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Project description:ImportanceGiven the rapidly rising dementia incidence, management of modifiable risk factors, such as hearing loss, is vital. Multiple studies have demonstrated an improvement of cognitive functioning in older adults with severe hearing loss after cochlear implantation; however, few of these studies, to the authors' knowledge, specifically analyzed participants achieving poor cognitive results preoperatively.ObjectiveTo evaluate the cognitive functioning of older adults with severe hearing loss at risk for mild cognitive impairment (MCI) before and after cochlear implantation.Design, setting, and participantsThis prospective, longitudinal cohort study performed at a single center reports data obtained over a 6-year period (April 2015 to September 2021) of an ongoing prospective, longitudinal cohort study on cochlear implant outcomes in older adults. A consecutive sample of older adults with severe hearing loss eligible for cochlear implantation was included. All participants obtained a Repeatable Battery for the Assessment of Neuropsychological Status for hearing-impaired patients (RBANS-H) total score indicative of MCI preoperatively. Participants were assessed before cochlear implant activation and 12 months after cochlear implant activation.InterventionThe intervention consisted of cochlear implantation.Main outcome and measureThe primary outcome measure was cognition, measured by the RBANS-H.ResultsA total of 21 older adult cochlear implant candidates were included in the analysis (mean [SD] age, 72 [9] years; 13 [62%] men). Cochlear implantation was associated with an improvement of overall cognitive functioning 12 months after activation (median [IQR] percentile, 5 [2-8] vs 12 [7-19]; difference, 7 [95% CI, 2-12]). Eight participants (38%) surpassed the MCI cutoff (16th percentile) postoperatively, while the overall median cognitive score remained under this cutoff. In addition, participants' speech recognition in noise improved, with a lower score indicating improvement (mean [SD] score, +17.16 [5.45] vs +5.67 [6.3]; difference, -11.49 [95% CI, -14.26 to -8.72]), after cochlear implant activation. Improvement of speech recognition in noise was positively associated with improvement in cognitive functioning (rs, -0.48 [95% CI, -0.69 to -0.19]). Years of education, sex, RBANS-H version, and symptoms of depression and anxiety were not related to the evolution in RBANS-H scores.Conclusions and relevanceIn this prospective, longitudinal cohort study, cognitive functioning and speech perception in noise showed a clinically meaningful improvement 12 months after cochlear implant activation in older adults with severe hearing loss at risk for MCI, suggesting that cochlear implantation is not contraindicated in cochlear implant candidates with cognitive decline and should be considered after multidisciplinary evaluation.

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Dataset Information

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.

Publications

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.

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