Genetics and genomics in prostate cancer

Prostate cancer genetics

• Prostate carcinoma is a multifactorial disease influenced by both environmental and genetic factors.

• Positive family history is the strongest epidemiological risk factor after advancing age and ethnic background.

• Prostate carcinoma can be divided into three groups: hereditary, familial, and sporadic; up to 85% of all prostate cancers are sporadic and only 10%–15% are genetically determined.

• Hereditary prostate cancer, compatible with Mendelian inheritance criteria, is demonstrated only in 5% of cases with a family history of prostate cancer, whereas familial prostate cancer accounts for approximately 13%–25% of cases.

• Apart from RNaseL, ElaC2, MSR1, HOXB13, as well as the low number of CAG repeats in the androgen receptor gene, there are no other identified high-risk genetic variants which might be considered responsible for hereditary prostate cancer.

• Hereditary prostate cancer X-linked (HPCX) gene (q27–28 region on chromosome X) has been suggested to be involved in hereditary prostate carcinoma; HPCX variants seem to be associated with prostate tumor aggressiveness.

• Prostate cancer-susceptibility locus, HPC20, which maps to 20q13, may potentially play a role in prostate cancer diagnosed at an older age.

• Familial prostate cancer is a genetically heterogeneous disease, related to changes in many gene loci rather than to a specific major susceptibility gene.

• BRCA1 has been associated with an increased risk of sporadic prostate cancer (3.5-fold), even though germline mutations have only been observed in 0.44% of prostate cancer cases.

• Germline mutations in BRCA2 lead to an increased risk of prostate cancer, with relative risks estimated as high as 5-fold to 7-fold; some evidence suggests a more important role in prostate cancer presenting at a younger age (≤65 years).

• The lifetime risk of prostate cancer in BRCA2 mutation carriers has been estimated to be 20%, while for BRCA1 the risk is 9.5% by age 65 years, similar to that in non-carriers.

• Monoallelic and biallelic PTEN loss has been reported in approximately 42% and 10% of prostate cancers, respectively.

Prostate cancer genomics