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Germline mutations in PPFIBP2 are associated with lethal prostate cancer
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| Zeitschriftentitel: | The Prostate |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , |
| In: | The Prostate, 78, 2018, 16, S. 1222-1228 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Wu, Yishuo Yu, Hongjie Zheng, Siqun Lilly Feng, Bingjian Kapron, Ashley L. Na, Rong Boyle, Julie L. Shah, Sameep Shi, Zhuqing Ewing, Charles M. Wiley, Kathleen E. Luo, Jun Walsh, Patrick C. Carter, Herbert Ballentine Helfand, Brian T. Cooney, Kathleen A. Xu, Jianfeng Isaacs, William B. Wu, Yishuo Yu, Hongjie Zheng, Siqun Lilly Feng, Bingjian Kapron, Ashley L. Na, Rong Boyle, Julie L. Shah, Sameep Shi, Zhuqing Ewing, Charles M. Wiley, Kathleen E. Luo, Jun Walsh, Patrick C. Carter, Herbert Ballentine Helfand, Brian T. Cooney, Kathleen A. Xu, Jianfeng Isaacs, William B. |
|---|---|
| author |
Wu, Yishuo Yu, Hongjie Zheng, Siqun Lilly Feng, Bingjian Kapron, Ashley L. Na, Rong Boyle, Julie L. Shah, Sameep Shi, Zhuqing Ewing, Charles M. Wiley, Kathleen E. Luo, Jun Walsh, Patrick C. Carter, Herbert Ballentine Helfand, Brian T. Cooney, Kathleen A. Xu, Jianfeng Isaacs, William B. |
| spellingShingle |
Wu, Yishuo Yu, Hongjie Zheng, Siqun Lilly Feng, Bingjian Kapron, Ashley L. Na, Rong Boyle, Julie L. Shah, Sameep Shi, Zhuqing Ewing, Charles M. Wiley, Kathleen E. Luo, Jun Walsh, Patrick C. Carter, Herbert Ballentine Helfand, Brian T. Cooney, Kathleen A. Xu, Jianfeng Isaacs, William B. The Prostate Germline mutations in PPFIBP2 are associated with lethal prostate cancer Urology Oncology |
| author_sort |
wu, yishuo |
| spelling |
Wu, Yishuo Yu, Hongjie Zheng, Siqun Lilly Feng, Bingjian Kapron, Ashley L. Na, Rong Boyle, Julie L. Shah, Sameep Shi, Zhuqing Ewing, Charles M. Wiley, Kathleen E. Luo, Jun Walsh, Patrick C. Carter, Herbert Ballentine Helfand, Brian T. Cooney, Kathleen A. Xu, Jianfeng Isaacs, William B. 0270-4137 1097-0045 Wiley Urology Oncology http://dx.doi.org/10.1002/pros.23697 <jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:italic>PPFIBP2</jats:italic>. Mutation carrier rates and association with lethal PCa were analyzed using the Fisher exact test, logistic regression, and Kaplan‐Meier survival analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the entire study population, eight patients, all of European ancestry, were identified as carrying <jats:italic>PPFIBP2</jats:italic> 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, <jats:italic>P</jats:italic> = 0.0029. The estimated Odds Ratio (OR) of carrying <jats:italic>PPFIBP2</jats:italic> mutation for lethal PCa was 13.8 in European American population. The <jats:italic>PPFIBP2</jats:italic> 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%, <jats:italic>P</jats:italic> = 1.92 × 10<jats:sup>−5</jats:sup>) and in 498 men with localized PCa from The Cancer Genome Atlas cohort (TCGA) cohort (carrier rate of 0%, <jats:italic>P</jats:italic> = 0.0058). Survival analysis in European American lethal cases revealed <jats:italic>PPFIBP2</jats:italic> 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, <jats:italic>P</jats:italic> = 0.034).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>While larger studies are needed, germline mutations in a novel gene, <jats:italic>PPFIBP2</jats:italic>, differentiated risk for lethal PCa from low‐risk cases and were associated with shorter survival times after diagnosis.</jats:p></jats:sec> Germline mutations in <i>PPFIBP2</i> are associated with lethal prostate cancer The Prostate |
| doi_str_mv |
10.1002/pros.23697 |
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Online |
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Medizin |
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Wiley, 2018 |
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0270-4137 1097-0045 |
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The Prostate |
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| title |
Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_unstemmed |
Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_full |
Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_fullStr |
Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_full_unstemmed |
Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_short |
Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_sort |
germline mutations in <i>ppfibp2</i> are associated with lethal prostate cancer |
| topic |
Urology Oncology |
| url |
http://dx.doi.org/10.1002/pros.23697 |
| publishDate |
2018 |
| physical |
1222-1228 |
| description |
<jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:italic>PPFIBP2</jats:italic>. Mutation carrier rates and association with lethal PCa were analyzed using the Fisher exact test, logistic regression, and Kaplan‐Meier survival analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the entire study population, eight patients, all of European ancestry, were identified as carrying <jats:italic>PPFIBP2</jats:italic> 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, <jats:italic>P</jats:italic> = 0.0029. The estimated Odds Ratio (OR) of carrying <jats:italic>PPFIBP2</jats:italic> mutation for lethal PCa was 13.8 in European American population. The <jats:italic>PPFIBP2</jats:italic> 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%, <jats:italic>P</jats:italic> = 1.92 × 10<jats:sup>−5</jats:sup>) and in 498 men with localized PCa from The Cancer Genome Atlas cohort (TCGA) cohort (carrier rate of 0%, <jats:italic>P</jats:italic> = 0.0058). Survival analysis in European American lethal cases revealed <jats:italic>PPFIBP2</jats:italic> 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, <jats:italic>P</jats:italic> = 0.034).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>While larger studies are needed, germline mutations in a novel gene, <jats:italic>PPFIBP2</jats:italic>, differentiated risk for lethal PCa from low‐risk cases and were associated with shorter survival times after diagnosis.</jats:p></jats:sec> |
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| author | Wu, Yishuo, Yu, Hongjie, Zheng, Siqun Lilly, Feng, Bingjian, Kapron, Ashley L., Na, Rong, Boyle, Julie L., Shah, Sameep, Shi, Zhuqing, Ewing, Charles M., Wiley, Kathleen E., Luo, Jun, Walsh, Patrick C., Carter, Herbert Ballentine, Helfand, Brian T., Cooney, Kathleen A., Xu, Jianfeng, Isaacs, William B. |
| author_facet | Wu, Yishuo, Yu, Hongjie, Zheng, Siqun Lilly, Feng, Bingjian, Kapron, Ashley L., Na, Rong, Boyle, Julie L., Shah, Sameep, Shi, Zhuqing, Ewing, Charles M., Wiley, Kathleen E., Luo, Jun, Walsh, Patrick C., Carter, Herbert Ballentine, Helfand, Brian T., Cooney, Kathleen A., Xu, Jianfeng, Isaacs, William B., Wu, Yishuo, Yu, Hongjie, Zheng, Siqun Lilly, Feng, Bingjian, Kapron, Ashley L., Na, Rong, Boyle, Julie L., Shah, Sameep, Shi, Zhuqing, Ewing, Charles M., Wiley, Kathleen E., Luo, Jun, Walsh, Patrick C., Carter, Herbert Ballentine, Helfand, Brian T., Cooney, Kathleen A., Xu, Jianfeng, Isaacs, William B. |
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| description | <jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:italic>PPFIBP2</jats:italic>. Mutation carrier rates and association with lethal PCa were analyzed using the Fisher exact test, logistic regression, and Kaplan‐Meier survival analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the entire study population, eight patients, all of European ancestry, were identified as carrying <jats:italic>PPFIBP2</jats:italic> 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, <jats:italic>P</jats:italic> = 0.0029. The estimated Odds Ratio (OR) of carrying <jats:italic>PPFIBP2</jats:italic> mutation for lethal PCa was 13.8 in European American population. The <jats:italic>PPFIBP2</jats:italic> 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%, <jats:italic>P</jats:italic> = 1.92 × 10<jats:sup>−5</jats:sup>) and in 498 men with localized PCa from The Cancer Genome Atlas cohort (TCGA) cohort (carrier rate of 0%, <jats:italic>P</jats:italic> = 0.0058). Survival analysis in European American lethal cases revealed <jats:italic>PPFIBP2</jats:italic> 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, <jats:italic>P</jats:italic> = 0.034).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>While larger studies are needed, germline mutations in a novel gene, <jats:italic>PPFIBP2</jats:italic>, differentiated risk for lethal PCa from low‐risk cases and were associated with shorter survival times after diagnosis.</jats:p></jats:sec> |
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| imprint | Wiley, 2018 |
| imprint_str_mv | Wiley, 2018 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-D161, DE-Zi4, DE-Gla1, DE-15, DE-Pl11, DE-Rs1, DE-14, DE-105, DE-Ch1, DE-L229 |
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| spelling | Wu, Yishuo Yu, Hongjie Zheng, Siqun Lilly Feng, Bingjian Kapron, Ashley L. Na, Rong Boyle, Julie L. Shah, Sameep Shi, Zhuqing Ewing, Charles M. Wiley, Kathleen E. Luo, Jun Walsh, Patrick C. Carter, Herbert Ballentine Helfand, Brian T. Cooney, Kathleen A. Xu, Jianfeng Isaacs, William B. 0270-4137 1097-0045 Wiley Urology Oncology http://dx.doi.org/10.1002/pros.23697 <jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:italic>PPFIBP2</jats:italic>. Mutation carrier rates and association with lethal PCa were analyzed using the Fisher exact test, logistic regression, and Kaplan‐Meier survival analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the entire study population, eight patients, all of European ancestry, were identified as carrying <jats:italic>PPFIBP2</jats:italic> 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, <jats:italic>P</jats:italic> = 0.0029. The estimated Odds Ratio (OR) of carrying <jats:italic>PPFIBP2</jats:italic> mutation for lethal PCa was 13.8 in European American population. The <jats:italic>PPFIBP2</jats:italic> 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%, <jats:italic>P</jats:italic> = 1.92 × 10<jats:sup>−5</jats:sup>) and in 498 men with localized PCa from The Cancer Genome Atlas cohort (TCGA) cohort (carrier rate of 0%, <jats:italic>P</jats:italic> = 0.0058). Survival analysis in European American lethal cases revealed <jats:italic>PPFIBP2</jats:italic> 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, <jats:italic>P</jats:italic> = 0.034).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>While larger studies are needed, germline mutations in a novel gene, <jats:italic>PPFIBP2</jats:italic>, differentiated risk for lethal PCa from low‐risk cases and were associated with shorter survival times after diagnosis.</jats:p></jats:sec> Germline mutations in <i>PPFIBP2</i> are associated with lethal prostate cancer The Prostate |
| spellingShingle | Wu, Yishuo, Yu, Hongjie, Zheng, Siqun Lilly, Feng, Bingjian, Kapron, Ashley L., Na, Rong, Boyle, Julie L., Shah, Sameep, Shi, Zhuqing, Ewing, Charles M., Wiley, Kathleen E., Luo, Jun, Walsh, Patrick C., Carter, Herbert Ballentine, Helfand, Brian T., Cooney, Kathleen A., Xu, Jianfeng, Isaacs, William B., The Prostate, Germline mutations in PPFIBP2 are associated with lethal prostate cancer, Urology, Oncology |
| title | Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_full | Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_fullStr | Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_full_unstemmed | Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_short | Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| title_sort | germline mutations in <i>ppfibp2</i> are associated with lethal prostate cancer |
| title_unstemmed | Germline mutations in PPFIBP2 are associated with lethal prostate cancer |
| topic | Urology, Oncology |
| url | http://dx.doi.org/10.1002/pros.23697 |