Genome-wide scan identifies role for AOX1 in prostate cancer survival Journal Article


Authors: Li, W.; Middha, M.; Bicak, M.; Sjoberg, D. D.; Vertosick, E.; Dahlin, A.; Häggström, C.; Hallmans, G.; Rönn, A. C.; Stattin, P.; Melander, O.; Ulmert, D.; Lilja, H.; Klein, R. J.
Article Title: Genome-wide scan identifies role for AOX1 in prostate cancer survival
Abstract: Background: Most men diagnosed with prostate cancer have low-risk cancers. How to predict prostate cancer progression at the time of diagnosis remains challenging. Objective: To identify single nucleotide polymorphisms (SNPs) associated with death from prostate cancer. Design, setting, and participants: Blood samples from 11 506 men in Sweden were collected during 1991–1996. Of these, 1053 men were diagnosed with prostate cancer and 245 died from the disease. Stage and grade at diagnosis and outcome information were obtained, and DNA from all cases was genotyped. Outcome measurements and statistical analysis: A total of 6 126 633 SNPs were tested for association with prostate-cancer-specific survival time using a Cox proportional hazard model, adjusted for age, stage, and grade at diagnosis. A value of 1 × 10−6 was used as suggestive significance threshold. Positive candidate SNPs were tested for association with gene expression using expression quantitative trait locus analysis. Results and limitations: We found 12 SNPs at seven independent loci associated with prostate-cancer-specific survival time. One of 6 126 633 SNPs tested reached genome-wide significance (p < 5 × 10−8) and replicated in an independent cohort: rs73055188 (p = 5.27 × 10−9, per-allele hazard ratio [HR] = 2.27, 95% confidence interval [CI] 1.72–2.98) in the AOX1 gene. A second SNP reached a suggestive level of significance (p < 1 × 10−6) and replicated in an independent cohort: rs2702185 (p = 7.1 × 10−7, per-allele HR = 2.55, 95% CI = 1.76–3.69) in the SMG7 gene. The SNP rs73055188 is correlated with AOX1 expression levels, which is associated with biochemical recurrence of prostate cancer in independent cohorts. This association is yet to be validated in other ethnic groups. Conclusions: The SNP rs73055188 at the AOX1 locus is associated with prostate-cancer-specific survival time, and AOX1 gene expression level is correlated with biochemical recurrence of prostate cancer. Patient summary: We identify two genetic markers that are associated with prostate-cancer-specific survival time. We performed genome-wide association studies and found single nucleotide polymorphisms (SNPs) at seven independent loci associated with prostate-cancer-specific survival time. Two SNPs replicated in an independent cohort. The SNP rs73055188 at AOX1 is associated with AOX1 gene expression level, which is correlated with biochemical recurrence. © 2018 European Association of Urology
Keywords: adult; aged; survival analysis; major clinical study; single nucleotide polymorphism; cancer patient; follow up; cancer diagnosis; allele; cohort analysis; genome-wide association study; cancer mortality; prostate cancer; sweden; survival time; blood sampling; cancer specific survival; tumor gene; biochemical recurrence; gene expression level; human; male; priority journal; article; expression quantitative trait locus; aox1; aox1 gene
Journal Title: European Urology
Volume: 74
Issue: 6
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2018-12-01
Start Page: 710
End Page: 719
Language: English
DOI: 10.1016/j.eururo.2018.06.021
PUBMED: 30289108
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
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MSK Authors
  1. Hans Gosta Lilja
    286 Lilja
  2. Daniel D. Sjoberg
    138 Sjoberg
  3. Hans David Staffan Ulmert
    49 Ulmert