Prevalence of the HOXB13 G84E germline mutation in British men and correlation with prostate cancer risk, tumour characterisitics and clinical outcomes
Menée au Royaume-Uni à partir des données de deux cohortes "UK Genetic Prostate Cancer Study" et "UK ProtecT study" portant sur 8 652 cas et 5 252 témoins, cette étude évalue l'association entre une mutation constitutionnelle du gène HOXB13, le risque de cancer de la prostate, les caractéristiques de la tumeur et la survie des patients
Background : A rare recurrent missense variant in HOXB13 (rs138213197 / G84E) was recently reported to be associated with hereditary prostate cancer. Population based studies have established that since the frequency of this SNP varies between geographic regions the associated proportion of prostate cancer (PrCa) risk contribution is also highly variable by country. Patients and Methods : This is the largest comprehensive case-control study assessing the prevalence of the HOXB13 G84E variant to date and is the first in the UK population. We genotyped 8652 men diagnosed with PrCa within the UK Genetic Prostate Cancer Study (UKGPCS) and 5252 healthy men from the UK ProtecT study. Results : HOXB13 G84E was identified in 0.5% of the healthy controls and 1.5% of the PrCa cases and it was associated with a 2.93-fold increased risk of PrCa [95%CI:1.94-4.59; P 6.27x10−8]. The risk was even higher among men with family history of PrCa (OR=4.53, 95%CI: 2.86-7.34; P 3.1x10−8) and in young-onset PrCa (diagnosed up to the age of 55 years; OR=3.11, 95%CI: 1.98-5.00; P 6.1x10−7). There was no significant association between Gleason Score, presenting PSA, TNM stage or NCCN risk group and carrier status. HOXB13 G84E was not associated with overall or cancer specific survival. We found that the polygenic PrCa risk score (PR score), calculated using the 71 known single nucleotide polymorphisms (SNPs) associated with PrCa and the HOXB13 G84E variant act multiplicatively on PrCa risk. Based on the estimated prevalence and risk, this rare variant explains about 1% of the familial risk of PrCa in the UK population. Conclusions : The clinical importance of HOXB13 G84E in PrCa management has not been established. This variant was found to have no effect on prognostic implications but could be used for stratifying screening, by identifying men at high risk.
Annals of Oncology 2015