The Family History Effect:

An Increase in Probability of Prostate Cancer

Categories: Spring 2017
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Finding the genetic origins of prostate cancer may seem an insurmountable task, but research is progressing toward a clearer understanding. © Dan Oldfield

A large analysis of brothers in the Prostate Cancer data Base Sweden (PCBaSe) showed that men with a family history of prostate cancer were more likely to get clinically significant prostate cancer.

The study included 51,897 brothers of 32,807 men with prostate cancer. At age 65, the probability of a man developing non-low-risk prostate cancer in the overall population was 2.8%, compared to 7.3% for men who had one brother with prostate cancer. At age 75, the probability of developing non-low-risk prostate cancer in the overall population was 8.9%, compared to 18.8% for men with an affected brother.

The probability of developing highrisk prostate cancer was even higher. At age 65, the probability of developing high-risk prostate cancer was 1.4% in the overall population, compared to 3.0% for men with one affected brother. At age 75, the probability of high-risk prostate cancer was 5.2% in the overall population, compared to 8.9% for men with one brother affected by prostate cancer.

Probabilities were higher for men with stronger family history of prostate cancer. For example, a man with two brothers with prostate cancer had a 13.6% probability of developing highrisk prostate cancer at age 75.

Non-lowrisk cancer was defined as a having at least one the following: Gleason score 7 or higher, PSA of 10 ng/mL or higher, T3–4 (cancer has spread outside the prostate), N1 (cancer has spread to one or more nearby lymph nodes), and/or M1 (cancer has spread beyond nearby lymph nodes). High-risk prostate cancer was defined as Gleason score 8 or higher and/or one of the following: T3–4, PSA 20 ng/mL or higher, N1, M1.

J Natl Cancer Inst. 2016 Jul 10;108(10). pii: djw110. doi: 10.1093/jnci/djw110. Print 2016 Oct.

Genetic Mutations in Prostate Tumors in African American Men

Dr. Catalona co-authored a study that used genetic sequencing to characterize somatic gene mutations in aggressive prostate tumors from 24 African American patients. Gene mutations are permanent alterations in a gene’s DNA sequence. Somatic mutations are acquired, not inherited; they occur at some point in a person’s life and are not passed on to the next generation.

The researchers observed several mutation patterns consistent with previous studies and identified mutation patterns that appeared specific to or more common in African American patients, including a novel gene fusion that occurred in 17% of the patients.

Previous whole genome or exome tumor-sequencing studies of prostate cancer have primarily focused on men with European ancestry.

Cancer Res. 2016 Apr 1;76(7):1860-8. doi: 10.1158/0008-5472.CAN-15-1787. Epub 2016 Feb 26.

African American men are two times more likely to develop and die of prostate cancer than men of other ancestries.

The International Consortium for Prostate Cancer Genetics

The International Consortium for Prostate Cancer Genetics (ICPCG) is a collaborative group of cancer research investigators conducting genome-wide association studies (GWAS) on familial prostate cancer. Dr. Catalona is Principal Investigator of the Northwestern University site of the ICPCG.

By collaborating across multiple institutions, the researchers can collect and study the large numbers of DNA samples needed to map and identify prostate cancer susceptibility genes. As of last year, the ICPCG has performed sequencing of 2,511 familial prostate cancer cases and 1,382 controls across its 21 sites.

Recently published research from ICPCG researchers supported evidence associating certain SNPs (individual gene locations) with prostate cancer in population-based studies. They also found strong evidence for a rare grouping of inherited genes associated with prostate cancer. Results from ICPCG research will be incorporated into Dr. Catalona’s SPORE project on germline genetic variants.

Hum Genet. 2016 Aug;135(8):923-38. doi: 10.1007/s00439-016-1690-6. Epub 2016 Jun 4.

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