File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Germline mutations in PPFIBP2 are associated with lethal prostate cancer

TitleGermline mutations in PPFIBP2 are associated with lethal prostate cancer
Authors
Keywordsgermline
lethal prostate cancer
loss of function (LOF)
mutation
PPFIBP2
Issue Date2018
Citation
Prostate, 2018, v. 78, n. 16, p. 1222-1228 How to Cite?
AbstractBackground: Few genes have germline mutations which predispose men to more aggressive prostate cancer (PCa). This study evaluated the contribution of germline loss of function (LOF) variants in PPFIBP2 to risk of lethal PCa. Methods: A case-case study of 1414 PCa patients with lethal PCa and low-risk localized PCa was performed. Germline DNA samples from these patients were sequenced for PPFIBP2. Mutation carrier rates and association with lethal PCa were analyzed using the Fisher exact test, logistic regression, and Kaplan-Meier survival analysis. Results: In the entire study population, eight patients, all of European ancestry, were identified as carrying PPFIBP2 pathogenic or likely pathogenic mutations. Seven (1.52%) of 462 lethal PCa patients were carriers compared with only one (0.12%) carrier in 810 low-risk PCa patients, P = 0.0029. The estimated Odds Ratio (OR) of carrying PPFIBP2 mutation for lethal PCa was 13.8 in European American population. The PPFIBP2 loss-of-function mutation carrier rate in lethal PCa cases was also higher than in 33 370 non-Finnish European individuals from the Exome Aggregation Consortium (ExAC) (carrier rate of 0.17%, P = 1.92 × 10−5) and in 498 men with localized PCa from The Cancer Genome Atlas cohort (TCGA) cohort (carrier rate of 0%, P = 0.0058). Survival analysis in European American lethal cases revealed PPFIBP2 mutation status as an independent predictor of shorter survival after adjusting for age at diagnosis, PSA at diagnosis, and genetic background (hazard ratio = 2.62, P = 0.034). Conclusions: While larger studies are needed, germline mutations in a novel gene, PPFIBP2, differentiated risk for lethal PCa from low-risk cases and were associated with shorter survival times after diagnosis.
Persistent Identifierhttp://hdl.handle.net/10722/314356
ISSN
2021 Impact Factor: 4.012
2020 SCImago Journal Rankings: 1.295

 

DC FieldValueLanguage
dc.contributor.authorWu, Yishuo-
dc.contributor.authorYu, Hongjie-
dc.contributor.authorZheng, Siqun Lilly-
dc.contributor.authorFeng, Bingjian-
dc.contributor.authorKapron, Ashley L.-
dc.contributor.authorNa, Rong-
dc.contributor.authorBoyle, Julie L.-
dc.contributor.authorShah, Sameep-
dc.contributor.authorShi, Zhuqing-
dc.contributor.authorEwing, Charles M.-
dc.contributor.authorWiley, Kathleen E.-
dc.contributor.authorLuo, Jun-
dc.contributor.authorWalsh, Patrick C.-
dc.contributor.authorCarter, Herbert Ballentine-
dc.contributor.authorHelfand, Brian T.-
dc.contributor.authorCooney, Kathleen A.-
dc.contributor.authorXu, Jianfeng-
dc.contributor.authorIsaacs, William B.-
dc.date.accessioned2022-07-20T12:03:44Z-
dc.date.available2022-07-20T12:03:44Z-
dc.date.issued2018-
dc.identifier.citationProstate, 2018, v. 78, n. 16, p. 1222-1228-
dc.identifier.issn0270-4137-
dc.identifier.urihttp://hdl.handle.net/10722/314356-
dc.description.abstractBackground: Few genes have germline mutations which predispose men to more aggressive prostate cancer (PCa). This study evaluated the contribution of germline loss of function (LOF) variants in PPFIBP2 to risk of lethal PCa. Methods: A case-case study of 1414 PCa patients with lethal PCa and low-risk localized PCa was performed. Germline DNA samples from these patients were sequenced for PPFIBP2. Mutation carrier rates and association with lethal PCa were analyzed using the Fisher exact test, logistic regression, and Kaplan-Meier survival analysis. Results: In the entire study population, eight patients, all of European ancestry, were identified as carrying PPFIBP2 pathogenic or likely pathogenic mutations. Seven (1.52%) of 462 lethal PCa patients were carriers compared with only one (0.12%) carrier in 810 low-risk PCa patients, P = 0.0029. The estimated Odds Ratio (OR) of carrying PPFIBP2 mutation for lethal PCa was 13.8 in European American population. The PPFIBP2 loss-of-function mutation carrier rate in lethal PCa cases was also higher than in 33 370 non-Finnish European individuals from the Exome Aggregation Consortium (ExAC) (carrier rate of 0.17%, P = 1.92 × 10−5) and in 498 men with localized PCa from The Cancer Genome Atlas cohort (TCGA) cohort (carrier rate of 0%, P = 0.0058). Survival analysis in European American lethal cases revealed PPFIBP2 mutation status as an independent predictor of shorter survival after adjusting for age at diagnosis, PSA at diagnosis, and genetic background (hazard ratio = 2.62, P = 0.034). Conclusions: While larger studies are needed, germline mutations in a novel gene, PPFIBP2, differentiated risk for lethal PCa from low-risk cases and were associated with shorter survival times after diagnosis.-
dc.languageeng-
dc.relation.ispartofProstate-
dc.subjectgermline-
dc.subjectlethal prostate cancer-
dc.subjectloss of function (LOF)-
dc.subjectmutation-
dc.subjectPPFIBP2-
dc.titleGermline mutations in PPFIBP2 are associated with lethal prostate cancer-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/pros.23697-
dc.identifier.pmid30043417-
dc.identifier.scopuseid_2-s2.0-85055880181-
dc.identifier.volume78-
dc.identifier.issue16-
dc.identifier.spage1222-
dc.identifier.epage1228-
dc.identifier.eissn1097-0045-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats