It has recently been shown that the majority of prostate cancers harbor a chromosomal rearrangement that fuses the gene for an androgen-regulated prostate-specific serine protease, TMPRSS2, with a member of the ETS family of transcription factors, most commonly ERG. These are among the most common genetic alterations in any human solid tumor.
This knowledge may provide us with clues to prostate carcinogenesis, and may lead to the development of important molecular-based biomarkers for patients with localized prostate cancer. The most common variant is fusion between the 5'-untranslated region of TMPRSS2 and the 3' region of ERG. However, over 20 other fusion variants have now been described (involving over 10 different genes) and the number of variants continues to grow. Fusion products can be identified by several techniques, including FISH, RT-PCR, and expression profiling using exon arrays.
The protein products associated with the fusion transcripts have not been characterized, and the phenotypic expression of the various products of gene fusion on prostate cancer histology, or on the clinical course of cancer, are not yet understood. Nonetheless, several early cohort studies suggest that the presence of the TMPRSS2:ERG fusion product is associated with relatively poor cancer-specific survival and most likely defines a distinct class of prostate cancer with potential implications for early diagnosis, prognosis, and rational therapeutic targeting.
Prostate cancer is the most common type of cancer diagnosed among American men, affecting one in six men during their lifetime. In 2008, an estimated 186,000 men will have been diagnosed with prostate cancer, according to the American Cancer Society. Currently, it is the second leading cause of death due to cancer in men. Fortunately, recent improvements in detection and treatment have significantly improved the outlook for men diagnosed with prostate cancer.
The most common risk factors for prostate cancer include age, family history, ethnicity and diet. Prostate cancer occurs more frequently in older men. Only 2 percent of prostate cancers are found in men younger than 56 years of age. Around 28 percent are detected in men 56 to 65 years of age and the other 70 percent are discovered in men older than 65 years.
Family history is the strongest risk factor for prostate cancer. A man with one close relative (such as a father or brother) with prostate cancer has twice the risk of developing prostate cancer as a man with no family history. If two close male relatives (such as a brother and a father) are affected, a man's lifetime risk of developing prostate cancer is increased five-fold. In addition, prostate cancer risk is about 60 percent higher in African-American men than in Caucasian men.
A diet high in fat and low in vegetables is associated with an increased risk for prostate cancer. The extent to which dietary factors contribute to and/or prevent prostate cancer is currently being researched.
The current recommendation is that all men at average risk should be screened once a year for prostate cancer beginning at age 50. Men who are at an increased risk for prostate cancer should begin screening earlier. African-American men and men with a family history of prostate cancer should begin screening at age 40. Screening consists of a rectal exam (DRE, or digital rectal exam) and a blood test (PSA, or prostate specific antigen).
Recent studies have concluded that a susceptibility to prostate cancer can be inherited. It is estimated that 5 to 10 percent of all prostate cancer cases are considered hereditary. This means that in some families, a genetic predisposition to develop prostate cancer can be passed down from parent to child. Currently there is no clinical testing for genes involved with prostate cancer. Only recently have studies begun to identify such genes. At present, many separate genes are thought to be involved: three on chromosome 1, one on chromosome 17, one on chromosome 20, one on chromosome X, and one on chromosome 8, as well as several others.
Additional research is needed to determine to what extent these genes are responsible for hereditary prostate cancer. Understanding how these genes are involved is critical for identifying men at increased risk, implementing proper screening procedures, and developing better treatments.
Men who are concerned about their hereditary risk because multiple family members have developed prostate cancer -- or there is an early age of diagnosis -- should discuss their concerns with their doctors and consider making an appointment with a trained genetic specialist.
Article first appeared in the Virginia Harkness Sawtelle Department of Radiation Oncology Newsletter, September 2009 issue.
