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 (PrCa). In a family-based analysis by The International Consortium for Prostate Cancer Genetics, the proportion of G84E mutation was highest 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 over 4000 PrCa cases and 5000 controls. In addition, the frequency was characterized in 986 breast (BrCa) and 442 colon cancer (CRC) cases. Genotyping was performed using TaqMan®, MassARRAY iPLEX and sequencing. Statistical analyses were performed using Fisher's exact test and overall survival was analyzed using Cox modeling. Results: Frequency was significantly higher among patients with PrCa, and highest among patients with family history of the disease, i.e. hereditary PrCa (8.4% vs. 1.0% in controls; odds ratio 8.8; 95% CI 4.9-15.7). The mutation contributed significantly to younger age (≤55 years) at onset and high PSA (≥20 ng/ml) at diagnosis. An association with increased PrCa risk in patients with prior BPH diagnosis was also revealed. No statistically significant evidence for G84E contribution in CRC risk was detected but a suggestive role for the mutation was seen in familial BrCa negative for BRCA1/2 founder mutations. Conclusions: These findings confirm the increased risk effect of G84E mutation in the Finnish population, particularly for early-onset PrCa and cases with substantially elevated PSA. Impact: This study confirms the overall importance of the HOXB13 G84E mutation in prostate cancer susceptibility.