Causes of Prostate Cancer
Understanding the risk factors of prostate cancer
The main causation or etiology of prostate cancer is not known with much confidence, but there has been a significant advancement at the behest of the National Cancer Institute within the past two decades to trace and understand the major potential causative and risk factors.
Age: This is considered to be the single most profound causative factor. It is estimated that as much as 70% of the diagnosed patients are over the age of 65. The median age at diagnosis is 67 years. One profound reason for this is that symptomatic detection of prostate cancer usually happens at an advanced stage of the disease due to insufficient and inadequate diagnostic strategies, severely curbing early identification.
Race: The epidemiology of prostate cancer suggests drastically different (varying between 60-100 folds) incidence rates across the globe. Asian people have the lowest incidence rates, while the African Americans are the most susceptible. Within the United States, the African Americans have a 60% more incidence rate than the Whites, inclusive of the Hispanics. Psychosocial, environmental and genetic predisposition has been suggested for the observed difference but none of the theories have been conclusively proved.
Genetic Predisposition: Low age prostate cancer incidence is most often associated with a genetic predisposition. BRCA1 and BRCA2, genes that have been indicated to malfunction in breast and ovarian cancers, preclude male family members to risk of prostate cancer. Also, children and siblings of prostate cancer patients are at a significantly higher risk for developing prostate cancer. A study in 2008 showed that there are two genes, Chemokine receptor 4 and Matrix metalloproteinase 9, that are overactive among African Americans compared to European-Americans affected by prostate cancer.
Dedicated projects funded by the National Cancer Institute are currently focusing on understanding the contribution of genetic difference and ensuing heritability as potential firing points for prostate cancer. One outstanding outcome of this was the identification of the RNase L gene. A multi-center study across USA, Israel and Finland found not only significant correlation between improperly functioning RNase L gene and early age incidence of prostate cancer, but also to the prognosis of the disease.
Hormones: Testosterone is the hormone required for normal functioning of the male reproductive system. But, malfunctioning amounts of testosterone and small amounts of estrogen (that are normally present in the male body) have been together linked with onset of prostate carcinoma. Of note, individuals with castrated levels of testosterone and eunuchs alike have an extremely low incidence of prostate carcinogenesis. Clinical studies are currently going on to further test the observations.
Obesity: No clear connection has been established yet. Few studies have correlated body-mass index (BMI) to incidence and mortality rates in prostate carcinogenesis. These studies have reported that morbidly obese (BMI> 35 kg.m-2) have 75% more risk than normal weight adults (BMI <25 kg.m-2), whereas overweight (BMI: 25-29.9 kg.m-2) and mildly obese (BMI 30-34.9 kg.m-2) have 25% and 46% increased risks, respectively. It must be added though that these studies did not show that the increased mortality was solely due to prostate cancer and not for metabolic disorders usually associated with obesity.
Life-Style: High fat diet, red meat, calcium supplements, Vitamin D and dairy products have all been indicated as dietary risk factors. On the other hand, Vitamin E, lycopene (found in tomatoes), selenium and phytoestrogens (found in soy protein) potentially reduces the risk of the disease. There have been some reports of smoking increasing the risk of incidence. Of note, alcohol consumption or the frequency of sex do not contribute to the risk quotient of prostate cancer.
Spurious Causes: A casual relationship of vasectomy to increased susceptibility to prostate carcinogenesis has been predicted but such studies have been overall inconclusive. Another condition which potentially increases the incidence rate is presence of high-grade prostatic intraepithelial neoplastic cells in the prostate gland.
Viral Infection: Xenotropic murine leukemia virus-related virus (XMRV) was recently identified in tissue samples of upto 27% of prostate cancer patients harboring a malfunctioned RNase L gene. The current hypothesis is that the functional RNase L gene fights XMRV by degrading its nuclear material, but the mutated form fails to do so giving rise to prostate cancer.
The male reproductive hormone, testosterone, helps in the multiplication of the virus further helping the disease. This discovery sort of ties up most of the other predicted causes into a whole plethora of succeeding events during the onset and progression of prostate carcinoma. More so, better understanding of the XMRV scenario will perhaps lead to novel anti-viral therapeutic strategies to potentially prevent both onset and progression of prostate cancer.