Association Between Germline HOXB13 G84E Mutation and Risk of Prostate Cancer

Akbari, Mohammad Reza; Trachtenberg, John; Lee, Justin; Tam, Stephanie; Bristow, Robert G.; Loblaw, Andrew; Narod, Steven A.; Nam, Robert K.

doi:10.1093/jnci/djs288

Cited by 64 publications

(55 citation statements)

References 9 publications

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“…Our study did not find this mutation among African American participants, which is consistent with prior studies (Ewing et al 2012; Witte et al 2013). Overall, the carrier frequency of 0.73 % in men with a family history in PRAP was higher than published controls (Ewing et al 2012; Chen et al 2013;Witte et al 2013; Laitinen et al 2013; Stott-Miller et al 2013; Akbari et al 2012; Kluzniak et al 2013; Schroeck et al 2013; Cybulski et al 2013). While PRAP is not fully representative of the US male population, our findings might indicate that a certain percentage of unaffected men with a family history of prostate cancer will carry the G84E mutation.…”

Section: Discussionmentioning

confidence: 63%

“…This carrier frequency of 0.73% from PRAP was placed in context of prevalence estimates from studies in the literature (Ewing et al 2012; Chen et al 2013; Witte et al 2013; Karlsson et al 2012; Laitinen et al 2013; Xu et al 2013; Stott-Miller et al 2013; Akbari et al 2012; Kluzniak et al 2013; Schroeck et al 2013; Cybulski et al 2013). Figure 2 shows the forest plot of carrier frequencies of the G84E mutation from reported studies.…”

Section: Resultsmentioning

confidence: 99%

“…Since the initial publication, several studies have been reported from various cohorts to better characterize this mutation and the risk associated with prostate cancer development. In particular, G84E appears to increase the risk for prostate cancer in men with a family history of prostate cancer and of Northern European descent (Xu et al 2013; Chen et al 2013; Witte et al 2013; Karlsson et al 2012; Laitinen et al 2013; Stott-Miller et al 2013; Akbari et al 2012; Kluzniak et al 2013; Schroeck et al 2013; Cybulski et al 2013). Since there is a spectrum of prevalence of the G84E mutation based primarily on strength of family cancer history and ancestry, our study was performed among high-risk men in a US cohort to describe the prevalence of G84E and place the findings in the context of reported studies of G84E in order to gain insight into the potential future role of G84E in prostate cancer risk assessment particularly for high-risk men.…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of the HOXB13 G84E Mutation Among Unaffected Men with a Family History of Prostate Cancer

Handorf

Crumpler

Gross

et al. 2013

Journal of Genetic Counseling

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HOXB13 (G84E) was reported to significantly increase risk for prostate cancer. The goal of the current analysis was to assess the prevalence of G84E in ethnically-diverse high-risk men undergoing prostate cancer screening and place the carrier frequency within the context of prevalence estimates from reported studies to gain insight into the future role of this mutation in genetic counseling. PRAP is a prostate cancer screening program for unaffected men ages 35–69 with a family history of prostate cancer or African descent. HOXB13 G84E was genotyped by pyrosequencing in 649 PRAP participants with available DNA. Prevalence of the mutation was calculated for PRAP and for reported studies and exact binomial confidence intervals were generated. Prevalence of the G84E mutation in non-African PRAP men was 0.73 %. When placed in context of the literature, this was higher than reported controls. One G84E mutation carrier was notably of Hispanic background. While the HOXB13 G84E mutation may be rare, there may be a future role in genetic testing for this mutation after further studies of clinical utility in assessing prostate cancer risk.

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Section: Discussionmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prevalence of the HOXB13 G84E Mutation Among Unaffected Men with a Family History of Prostate Cancer

Handorf

Crumpler

Gross

et al. 2013

Journal of Genetic Counseling

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show abstract

“…Recently, a variant in the HOXB13 gene was identified as the first germline mutation consistently and specifically associated with familial PrCa in men of European ancestry [1]. The increased PrCa risk conferred by the p.(Gly84Glu) mutation, also described as G84E, has been confirmed by several other authors [2][3][4][5][6] and it is now believed that this variant is a founder mutation originated in Scandinavia [4][5][6]. Subsequent studies have identified other HOXB13 variants in PrCa patients of African and Asian descent [1,2,7] and we have recently performed the first systematic full gene analysis of HOXB13 in early-onset and/or familial PrCa patients of Southern European origin [8].…”

Section: Introductionmentioning

confidence: 78%

The role of germline mutations in the BRCA1/2 and mismatch repair genes in men ascertained for early-onset and/or familial prostate cancer

et al. 2015

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Prostate cancer (PrCa) is one of the most common cancers diagnosed worldwide and 5-10 % of all cases are estimated to be associated with inherited predisposition. Even though there is strong evidence that the genetic component is significant in PrCa, the genetic etiology of familial and early-onset disease is largely unknown. Although it has been suggested that men from families with hereditary breast/ovarian cancer (HBOC) and, more recently, with Lynch syndrome may have an increased risk for PrCa, the contribution of these syndromes to PrCa predisposition in families ascertained for early-onset and/or familial PrCa, independently of the presence of other cancers in the family, is uncertain. To quantify the contribution of genes associated with HBOC and Lynch syndromes to PrCa predisposition, we have tested for germline mutations 460 early-onset and/or familial PrCa patients. All patients were screened for the six mutations that are particularly common in Portugal and 38 of them were selected for complete sequencing of BRCA1/2 and/or MLH1, MSH2 and MSH6. Two patients were found to harbor the same MSH2 mutation and a third patient carried a Portuguese BRCA2 founder mutation. None of the alterations were identified in 288 control subjects. Furthermore, we reviewed the 62 PrCa diagnoses in all HBOC (n = 161) and Lynch syndrome (n = 124) families previously diagnosed at our department, and found five other BRCA2 mutation carriers and two additional MSH2 mutation carriers. The clinicopathological characteristics of mutation carriers are in concordance with earlier data suggesting an aggressive PrCa phenotype and support the hypothesis that mutation carriers might benefit from targeted screening according to the gene mutated in the germline.

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“…Akbari et al performed a case-control study, sequencing germline DNA from peripheral leukocytes of 1,843 men diagnosed with prostate cancer and 2,225 controls to identify possible mutations in HOXB13 . The mutation was more prevalent in Caucasian men than in ethnically matched controls (0.7% vs. 0.1%, P = 0.01) (7). Finally, Karlsson et al genotyped samples from two population-based, Swedish, case-control studies and found the prevalence of the G84E mutation to be more than 1% in the general Swedish population, which is higher than we and others have reported for controls (around 0.1%) (8).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of HOXB13 mutation in a population of Ashkenazi Jewish men treated for prostate cancer

et al. 2013

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OBJECTIVE To determine the prevalence of HOXB13 G84E mutation in a population of prostate cancer patients of Ashkenazi Jewish heritage, an ethnic group common to the New York City area. MATERIALS AND METHODS A retrospective analysis of germline DNA samples from Ashkenazi Jewish men and a comparison group of non-Ashkenazi men treated for prostate cancer at our institution. Patients were genotyped for G84E using a TaqMan assay (Applied Biosystems). Positive cases were confirmed using Sanger sequencing. RESULTS Median age at prostate cancer diagnosis was 68 years for 889 Ashkenazi Jewish patients, 64 years for 920 non-Ashkenazi Jewish patients. The median follow up was 9 years for Ashkenazi Jewish patients and 8.8 years for non-Ashkenazi Jewish patients. Only 4 patients were found to be heterozygous carriers of G84E. They were all of non-Ashkenazi Jewish ancestry and were diagnosed at 70, 66, 78, and 49 years of age. Two of them presented with high-risk prostate cancer. The prevalence of G84E in the non-Ashkenazi sample was 0.4%. CONCLUSIONS HOXB13 G84E mutation was not observed in prostate cancer patients of Ashkenazi Jewish ancestry treated at our institution. Screening for G84E, therefore, may be unnecessary in Ashkenazi Jewish men if these results are validated by other studies.

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Association Between Germline HOXB13 G84E Mutation and Risk of Prostate Cancer

Cited by 64 publications

References 9 publications

Prevalence of the HOXB13 G84E Mutation Among Unaffected Men with a Family History of Prostate Cancer

Prevalence of the HOXB13 G84E Mutation Among Unaffected Men with a Family History of Prostate Cancer

The role of germline mutations in the BRCA1/2 and mismatch repair genes in men ascertained for early-onset and/or familial prostate cancer

Prevalence of HOXB13 mutation in a population of Ashkenazi Jewish men treated for prostate cancer

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