57837
document
HOXB13 G84E mutation in Finland : population-based analysis of prostate , breast , and colorectal cancer risk . BACKGROUND A recently identified germline mutation G84E in HOXB13 was shown to increase the risk of prostate cancer . In a family-based analysis by The International Consortium for Prostate Cancer Genetics ( ICPCG ) , the G84E mutation was most prevalent in families from the Nordic countries of Finland ( 22.4 % ) and Sweden ( 8.2 % ) . METHODS To further investigate the importance of G84E in the Finns , we determined its frequency in more than 4,000 prostate cancer cases and 5,000 controls . In addition , 986 breast cancer and 442 colorectal cancer ( CRC ) cases were studied . Genotyping was conducted using TaqMan , MassARRAY iPLEX , and sequencing . Statistical analyses were conducted using Fisher exact test , and overall survival was analyzed using Cox modeling . RESULTS The frequency of the G84E mutation was significantly higher among patients with prostate cancer and highest among patients with a family history of the disease , hereditary prostate cancer [ 8.4 % vs. 1.0 % in controls ; OR 8.8 ; 95 % confidence interval ( CI ) , 4.9-15.7 ] . The mutation contributed significantly to younger age ( ≤55 years ) at onset and high prostate-specific antigen ( PSA ; ≥20 ng/mL ) at diagnosis . An association with increased prostate cancer risk in patients with prior benign prostate hyperplasia ( BPH ) diagnosis was also revealed . No statistically significant evidence for a contribution in CRC risk was detected , but a suggestive role for the mutation was observed in familial BRCA1/2-negative breast cancer . CONCLUSIONS These findings confirm an increased cancer risk associated with the G84E mutation in the Finnish population , particularly for early-onset prostate cancer and cases with substantially elevated PSA . IMPACT This study confirms the overall importance of the HOXB13 G84E mutation in prostate cancer susceptibility .
57838
Intervention_Physical
HOXB13 G84E mutation
57839
Intervention_Physical
G84E in HOXB13
57840
Intervention_Physical
G84E mutation
57841
Intervention_Physical
Genotyping
57842
Outcome_Mortality
overall survival
57843
Outcome_Physical
frequency of the G84E mutation
57844
Outcome_Physical
mutation
57845
Outcome_Physical
increased prostate cancer risk
57846
Outcome_Physical
contribution in CRC risk
57847
Participant_Condition
Finland
57848
Participant_Condition
prostate , breast , and colorectal cancer risk
57849
Participant_Sample-size
4,000
57850
Participant_Sample-size
5,000
57851
Participant_Sample-size
986
57852
Participant_Sample-size
442