The association of BRCA1 and BRCA2 mutations with prostate cancer risk, frequency, and mortality: A meta‐analysis

Background A prior meta‐analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta‐analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in...

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Published in:	The Prostate Vol. 79; no. 8; pp. 880 - 895
Main Authors:	Oh, Mok, Alkhushaym, Nasser, Fallatah, Saad, Althagafi, Abdulhamid, Aljadeed, Rana, Alsowaida, Yazed, Jeter, Joanne, Martin, Jennifer R., Babiker, Hani M., McBride, Ali, Abraham, Ivo
Format:	Journal Article
Language:	English
Published:	United States Wiley Subscription Services, Inc 01.06.2019
Subjects:	BRCA1 BRCA1 protein BRCA1 Protein - genetics BRCA2 BRCA2 protein BRCA2 Protein - genetics Breast cancer Case-Control Studies Cohort Studies Genes, BRCA1 Genes, BRCA2 Genotyping Humans Male Meta-analysis Mortality Mutation Prostate cancer Prostatic Neoplasms - genetics Prostatic Neoplasms - mortality Statistical analysis Survival meta-analysis prostate cancer BRCA1 BRCA2
ISSN:	0270-4137, 1097-0045, 1097-0045
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Abstract	Background A prior meta‐analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta‐analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer‐specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers. Methods We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type ( BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age‐sex‐adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random‐effects models, in two‐sided statistical tests. Results A total of 8 cohort, 7 case‐control, 4 case‐series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier ( BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58‐2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03‐3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03‐1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64‐2.30) and CSS (HR = 2.63, 95% CI = 2.00‐3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11‐1.99) and CSS (HR = 1.07, 95% CI = 0.38‐2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers. Conclusions There is a 1.90‐fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64‐fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35‐fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high‐risk patients and guide clinical strategies for more effective treatments for patients with PCa.
AbstractList	A prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta-analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer-specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers. We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type ( BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age-sex-adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random-effects models, in two-sided statistical tests. A total of 8 cohort, 7 case-control, 4 case-series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier ( BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58-2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03-3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03-1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64-2.30) and CSS (HR = 2.63, 95% CI = 2.00-3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11-1.99) and CSS (HR = 1.07, 95% CI = 0.38-2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers. There is a 1.90-fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64-fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35-fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high-risk patients and guide clinical strategies for more effective treatments for patients with PCa. A prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta-analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer-specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers.BACKGROUNDA prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta-analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer-specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers.We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type ( BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age-sex-adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random-effects models, in two-sided statistical tests.METHODSWe searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type ( BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age-sex-adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random-effects models, in two-sided statistical tests.A total of 8 cohort, 7 case-control, 4 case-series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier ( BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58-2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03-3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03-1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64-2.30) and CSS (HR = 2.63, 95% CI = 2.00-3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11-1.99) and CSS (HR = 1.07, 95% CI = 0.38-2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers.RESULTSA total of 8 cohort, 7 case-control, 4 case-series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier ( BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58-2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03-3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03-1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64-2.30) and CSS (HR = 2.63, 95% CI = 2.00-3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11-1.99) and CSS (HR = 1.07, 95% CI = 0.38-2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers.There is a 1.90-fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64-fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35-fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high-risk patients and guide clinical strategies for more effective treatments for patients with PCa.CONCLUSIONSThere is a 1.90-fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64-fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35-fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high-risk patients and guide clinical strategies for more effective treatments for patients with PCa. BackgroundA prior meta‐analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta‐analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer‐specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers.MethodsWe searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type (BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age‐sex‐adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random‐effects models, in two‐sided statistical tests.ResultsA total of 8 cohort, 7 case‐control, 4 case‐series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier (BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58‐2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03‐3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03‐1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64‐2.30) and CSS (HR = 2.63, 95% CI = 2.00‐3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11‐1.99) and CSS (HR = 1.07, 95% CI = 0.38‐2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers.ConclusionsThere is a 1.90‐fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64‐fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35‐fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high‐risk patients and guide clinical strategies for more effective treatments for patients with PCa. Background A prior meta‐analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta‐analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer‐specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers. Methods We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type ( BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age‐sex‐adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random‐effects models, in two‐sided statistical tests. Results A total of 8 cohort, 7 case‐control, 4 case‐series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier ( BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58‐2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03‐3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03‐1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64‐2.30) and CSS (HR = 2.63, 95% CI = 2.00‐3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11‐1.99) and CSS (HR = 1.07, 95% CI = 0.38‐2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers. Conclusions There is a 1.90‐fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64‐fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35‐fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high‐risk patients and guide clinical strategies for more effective treatments for patients with PCa.
Author	Alkhushaym, Nasser Althagafi, Abdulhamid Jeter, Joanne Abraham, Ivo Babiker, Hani M. Aljadeed, Rana Oh, Mok Fallatah, Saad Alsowaida, Yazed Martin, Jennifer R. McBride, Ali
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/30900310$$D View this record in MEDLINE/PubMed
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Notes	Alkhushaym, Fallatah, Althaghfi, and Aljadeed have contributed equally to the study and their order of authorship was determined randomly. ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
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PublicationTitle	The Prostate
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Snippet	Background A prior meta‐analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an... A prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with... BackgroundA prior meta‐analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an...
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SubjectTerms	BRCA1 BRCA1 protein BRCA1 Protein - genetics BRCA2 BRCA2 protein BRCA2 Protein - genetics Breast cancer Case-Control Studies Cohort Studies Genes, BRCA1 Genes, BRCA2 Genotyping Humans Male Meta-analysis Mortality Mutation Prostate cancer Prostatic Neoplasms - genetics Prostatic Neoplasms - mortality Statistical analysis Survival
Title	The association of BRCA1 and BRCA2 mutations with prostate cancer risk, frequency, and mortality: A meta‐analysis
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