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Genetic risk of lung cancer associated with a single nucleotide polymorphism from EXO1: a meta analysis.

ABSTRACT: BACKGROUND/AIM:Several reports have investigated the role of exonuclease 1 (EXO1) rs1047840 in lung cancer risk in different ethnic populations. Nevertheless, the results have been controversial. We aimed to assess the possible association between EXO1 rs1047840 and risk of lung cancer in a meta-analysis. METHODS:Human hospital- or population-based studies released before December 16, 2013 were identified by systematic search of the PubMed and Embase databases. Data were extracted in duplicate from each study. An OR and 95% CI (odds ratio and 95% confidence interval) was calculated to evaluate the effects of EXO1 rs1047840 on lung carcinogenesis. RESULTS:A total of 1,114 lung cancer patients and 1,166 well-matched controls were analyzed in this study. The fixed-effects meta-analysis revealed that carriage of a single A allele, compared to the carriage of single G allele, was associated with 1.18 times increased risk of lung cancer (A vs. G: OR =1.18; 95% CI: 1.03-1.35; PHeterogeneity, 0.121). CONCLUSION:This first meta-analysis demonstrates that the A allele of EXO1 rs1047840 may confer modulating effects on the risk of lung cancer and could be used as a marker for early detection and primary prevention.

SUBMITTER: Tang J

PROVIDER: S-EPMC4565297 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genetic risk of lung cancer associated with a single nucleotide polymorphism from EXO1: a meta analysis.

Tang Jian J Tang Shengbo S Liu Jichun J Wu Qicai Q Wan Li L Xu Qirong Q

International journal of clinical and experimental medicine 20150715 7

<h4>Background/aim</h4>Several reports have investigated the role of exonuclease 1 (EXO1) rs1047840 in lung cancer risk in different ethnic populations. Nevertheless, the results have been controversial. We aimed to assess the possible association between EXO1 rs1047840 and risk of lung cancer in a meta-analysis.<h4>Methods</h4>Human hospital- or population-based studies released before December 16, 2013 were identified by systematic search of the PubMed and Embase databases. Data were extracted ...[more]

PMID: 26379914

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Project description:Importance:Few studies have evaluated the association between a single-nucleotide polymorphism-based genetic risk score (GRS) and patient age at prostate cancer (PCa) diagnosis. Objectives:To test the association between a GRS and patient age at PCa diagnosis and to compare the performance of a GRS with that of family history (FH) in PCa risk stratification. Design, Setting, and Participants:A cohort study of 3225 white men was conducted as a secondary analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) chemoprevention trial, a 4-year, randomized, double-blind, placebo-controlled multicenter study conducted from March 2003 to April 2009 to evaluate the safety and efficacy of dutasteride in reducing PCa events. Participants were confirmed to be cancer free by prostate biopsy (6-12 cores) within 6 months prior to the study and underwent 10 core biopsies every 2 years per protocol. The dates for performing data analysis were from July 2016 to October 2019. Interventions:A well-established, population-standardized GRS was calculated for each participant based on 110 known PCa risk-associated single-nucleotide polymorphisms, which is a relative risk compared with the general population. Men were classified into 3 GRS risk groups based on predetermined cutoff values: low (<0.50), average (0.50-1.49), and high (?1.50). Main Outcomes and Measures:Prostate cancer diagnosis-free survival among men of different risk groups. Results:Among 3225 men (median age, 63 years [interquartile range, 58-67 years]) in the study, 683 (21%) were classified as low risk, 1937 (60%) as average risk, and 605 (19%) as high risk based on GRS alone. In comparison, 2789 (86%) were classified as low or average risk and 436 (14%) as high risk based on FH alone. Men in higher GRS risk groups had a PCa diagnosis-free survival rate that was worse than that of those in the lower GRS risk group (?2?=?53.3; P?<?.001 for trend) and in participants with a negative FH of PCa (?2?=?45.5; P?<?.001 for trend). Combining GRS and FH further stratified overall genetic risk, indicating that 957 men (30%) were at high genetic risk (either high GRS or positive FH), 1667 men (52%) were at average genetic risk (average GRS and negative FH), and 601 men (19%) were at low genetic risk (low GRS and negative FH). The median PCa diagnosis-free survival was 74 years (95% CI, 73-75 years) for men at high genetic risk, 77 years (95% CI, 75 to >80 years) for men at average genetic risk, and more than 80 years (95% CI, >80 to >80 years) for men at low genetic risk. In contrast, the median PCa diagnosis-free survival was 73 years (95% CI, 71-76 years) for men with a positive FH and 77 years (95% CI, 76-79 years) for men with a negative FH. Conclusions and Relevance:This study suggests that a GRS is significantly associated with patient age at PCa diagnosis. Combining FH and GRS may better stratify inherited risk than FH alone for developing personalized PCa screening strategies.

Dataset Information

Genetic risk of lung cancer associated with a single nucleotide polymorphism from EXO1: a meta analysis.

Publications

Genetic risk of lung cancer associated with a single nucleotide polymorphism from EXO1: a meta analysis.

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