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DNA Analysis Finds First Gene Implicated in Prostate Cancer

Ben Leach
Published: Thursday, Jan 12, 2012

DNA strandA statistical analysis led to the discovery of the first high-risk genetic mutation associated with hereditary prostate cancer. This discovery could lead to better therapy for men diagnosed with the disease at a younger age and provides the first evidence of a gene being closely associated with the progression of prostate cancer.

The study initially pinpointed 202 genes in chromosome 17q21-22 with variants of the HOXB13 gene—a gene previously associated with prostate cancer in mice studies—demonstrating the most conclusive results.

In an initial group of 94 patients, 4 expressed a mutation in the G84E allele of HOXB13. This prompted testing within first- or second-degree relatives that also had prostate cancer, all were revealed to have the HOXB13 variation. This prompted the study’s authors to examine genotype data for 5083 unrelated men with prostate cancer and compare the data to 1401 men who had not been previously diagnosed with the disease.

The analysis found that men with prostate cancer had a 1.4% carrier frequency of the HOXB13 G84E allele compared to 0.1% in the study population without prostate cancer (P=8.5x10^7; OR=20.1, 95% CI [3.5 to 803.3]). Only 1 man in the non-prostate cancer group expressed the variant allele, compared to 72 men in the prostate cancer group. The study also found that younger men with prostate cancer were more likely to possess the allele variant compared to older men (52.9 years compared to 57.1 years, P=7.4x10^7).

The study was published in the New England Journal of Medicine and utilized DNA sequencing data from multiple medical centers. Since the study was based on statistical analysis the authors feel that more investigation is needed in order to prompt further examination into the possibility of other genetic mutations within this disease.

“This work suggests that future DNA sequencing studies using next-generation technology and study populations enriched for genetic influence…may identify additional rare variants that will contribute to familiar clustering of prostate cancer,” the authors wrote.
Ewing, CM, Ray, AM, Lange, EM, et al. Germline Mutations in HOXB13 and Prostate Cancer Risk. The New England Journal of Medicine. 2012;366:141-149.



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