Dataset Information

Association between germline homeobox B13 (HOXB13) G84E allele and prostate cancer susceptibility: a meta-analysis and trial sequential analysis.

ABSTRACT: Germline HOXB13 G84E mutation (rs138213197) has been described associated with prostate cancer (PCa) susceptibility but results of different studies are inconsistent. We conducted this meta-analysis to evaluate the specific role of this mutation. Relevant available studies were identified by searching the databases Pubmed, Embase and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. Subgroup analysis were performed to evaluate the specific role of rs138213197 in disease aggressiveness, diagnostic age and family history. Furthermore, trial sequential analysis (TSA) was conducted for the first time to estimate whether the evidence of the results is sufficient. Our results indicated that significant increased PCa susceptibility was associated with rs138213197 compared with non-carriers (OR = 3.38, 95% CI: 2.45-4.66). Besides, in subgroup analysis, HOXB13 G84E variant was obviously associated with early onset (OR = 2.90, 95% CI: 2.24-3.75), affected relatives (OR = 2.60, 95% CI 2.19-3.10) and highly aggressive disease (OR = 2.38, 95% CI 1.84-3.08). By TSA, the findings in the current study were based on sufficient evidence. Therefore, our results indicated that the G84E mutation in HOXB13 gene might increase susceptibility to PCa.

SUBMITTER: Zhang J

PROVIDER: S-EPMC5341860 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Association between germline homeobox B13 (HOXB13) G84E allele and prostate cancer susceptibility: a meta-analysis and trial sequential analysis.

Zhang Jianzhong J Xiao Li L Qin Zhiqiang Z Xu Aiming A Zhao Kai K Liang Chao C Miao Chenkui C Zhu Jundong J Chen Wei W Hua Yibo Y Liu Yiyang Y Zhang Chao C Yu Yajie Y Su Shifeng S Wang Zengjun Z

Oncotarget 20161001 41

Germline HOXB13 G84E mutation (rs138213197) has been described associated with prostate cancer (PCa) susceptibility but results of different studies are inconsistent. We conducted this meta-analysis to evaluate the specific role of this mutation. Relevant available studies were identified by searching the databases Pubmed, Embase and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. Subgroup analysis were performed to ...[more]

PMID: 27626483

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Project description:BackgroundThe homeobox B13 (HOXB13) G84E mutation has been recommended for use in genetic counselling for prostate cancer (PCa), but the magnitude of PCa risk conferred by this mutation is uncertain.ObjectiveTo obtain precise risk estimates for mutation carriers and information on how these vary by family history and other factors.Design, setting, and participantsTwo-fold: a systematic review and meta-analysis of published risk estimates, and a kin-cohort study comprising pedigree data on 11983 PCa patients enrolled during 1993-2014 from 189 UK hospitals and who had been genotyped for HOXB13 G84E.Outcome measurements and statistical analysisRelative and absolute PCa risks. Complex segregation analysis with ascertainment adjustment to derive age-specific risks applicable to the population, and to investigate how these vary by family history and birth cohort.Results and limitationsA meta-analysis of case-control studies revealed significant heterogeneity between reported relative risks (RRs; range: 0.95-33.0, p<0.001) and differences by case selection (p=0.007). Based on case-control studies unselected for PCa family history, the pooled RR estimate was 3.43 (95% confidence interval [CI] 2.78-4.23). In the kin-cohort study, PCa risk for mutation carriers varied by family history (p<0.001). There was a suggestion that RRs decrease with age, but this was not significant (p=0.068). We found higher RR estimates for men from more recent birth cohorts (p=0.004): 3.09 (95% CI 2.03-4.71) for men born in 1929 or earlier and 5.96 (95% CI 4.01-8.88) for men born in 1930 or later. The absolute PCa risk by age 85 for a male HOXB13 G84E carrier varied from 60% for those with no PCa family history to 98% for those with two relatives diagnosed at young ages, compared with an average risk of 15% for noncarriers. Limitations include the reliance on self-reported cancer family history.ConclusionsPCa risks for HOXB13 G84E mutation carriers are heterogeneous. Counselling should not be based on average risk estimates but on age-specific absolute risk estimates tailored to individual mutation carriers' family history and birth cohort.Patient summaryMen who carry a hereditary mutation in the homeobox B13 (HOXB13) gene have a higher than average risk for developing prostate cancer. In our study, we examined a large number of families of men with prostate cancer recruited across UK hospitals, to assess what other factors may contribute to this risk and to assess whether we could create a precise model to help in predicting a man's prostate cancer risk. We found that the risk of developing prostate cancer in men who carry this genetic mutation is also affected by a family history of prostate cancer and their year of birth. This information can be used to assess more personalised prostate cancer risks to men who carry HOXB13 mutations and hence better counsel them on more personalised risk management options, such as tailoring prostate cancer screening frequency.

Dataset Information

Association between germline homeobox B13 (HOXB13) G84E allele and prostate cancer susceptibility: a meta-analysis and trial sequential analysis.

Publications

Association between germline homeobox B13 (HOXB13) G84E allele and prostate cancer susceptibility: a meta-analysis and trial sequential analysis.

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