What causes prostate cancer?

What Causes Prostate Cancer

Prostate cancer develops through a complex interplay of non-modifiable risk factors (age, race, and genetics) and potentially modifiable environmental factors (diet, obesity, and lifestyle), though the exact mechanisms of carcinogenesis remain largely unknown.

Non-Modifiable Risk Factors

Age

• Age is the strongest risk factor for prostate cancer. More than 70% of all patients are older than 65 years at diagnosis, with a median age of 71 years 1
• More than 90% of prostate cancer deaths occur in men older than 65 years 1, 2
• A 50-year-old man has a 42% lifetime chance of developing histological prostate cancer, a 9.5% risk of clinically important disease, and a 2.9% risk of death from the disease 1, 2

Race and Ethnicity

• African American men experience the highest prostate cancer incidence rates worldwide, with 64% higher incidence and 2.3-fold higher mortality compared to white men 1, 2
• African American men present with higher-grade prostatic intraepithelial neoplasia (PIN), higher Gleason scores, and more advanced pathologic stage 1
• The disease is common in North America and northwestern Europe but rare in the Near East, Africa, and South America 1
• Studies show increased prostate cancer risk in immigrants from low-incidence countries (Japan, China) to the United States, suggesting environmental factors interact with genetic predisposition 1

Genetic and Familial Factors

• Approximately 9% of prostate malignancies are due to inherited predisposition 1, 3, 2
• Having one first-degree relative with prostate cancer increases risk 2.5-fold; two relatives confer a 5-fold risk; three relatives result in an 11-fold increased risk 1, 3
• Genetic analyses suggest an autosomal dominant inheritance pattern with high penetrance, conveying an 88% risk of cancer 1
• Approximately 42% of early-onset prostate cancers (diagnosed before age 55) may be inherited 1, 2

Specific Genetic Syndromes

• BRCA2 mutations are associated with a 2-6 fold increase in prostate cancer risk and more aggressive disease with reduced survival 1, 3, 2
• BRCA1 mutations show less consistent but still elevated risk 1, 3
• Lynch syndrome (germline mutations in MLH1, MSH2, MSH6, PMS2, or EPCAM) confers a 2-5 fold increased risk 1, 3
• Multiple chromosomes have been implicated, including chromosomes 1,8,10,16,17,20, and X, with chromosome 1 most strongly linked 1, 2
• Genes under investigation include PTEN/MMAC1, androgen receptor gene, 5α-reductase genes, and various others 1

Potentially Modifiable Risk Factors

Dietary Factors

• Diet is one of the most commonly cited environmental risk factors, with dietary fat particularly implicated 1
• Evidence suggests frequent consumption of dairy products and possibly red meat may enhance prostate cancer risk 4
• Protective factors may include increased intake of tomatoes (lycopene), cruciferous vegetables, and soy 5, 4
• Coffee consumption has been examined but results remain inconsistent 6
• Fish intake shows an inverse relationship with fatal prostate cancer specifically 4

Obesity and Physical Activity

• Obesity appears to have a dual effect: increased risk of aggressive prostate cancer but decreased risk of localized disease 6
• Both occupational and leisure-time physical activity are associated with reduced prostate cancer risk 6, 4
• Smoking shows weak association with prostate cancer incidence but positive correlation with prostate cancer mortality 4

Important Clinical Caveats

Heterogeneity of Disease

• The relationship between risk factors varies significantly by disease stage and aggressiveness 6, 4
• Some factors (smoking, obesity) show weak association with incidence but strong association with mortality 4
• This heterogeneity reflects different impacts on early versus late stages of carcinogenesis 4

Detection Bias

• Inconsistent associations in previous studies may partly result from uncontrolled detection bias due to widespread PSA screening 4
• Certain behavioral factors may be systematically related to the likelihood of undergoing screening examinations 4

Gene-Environment Interactions

• Multiple genes of relatively lower penetrance likely contribute to prostate cancer risk rather than a single gene 1
• Data concerning specific gene-environment interactions remain sparse 4
• Future research should account for genetic characteristics when examining environmental exposures 6

Baseline PSA as a Predictor

• Baseline PSA value is a stronger predictive factor than family history or race alone 1, 3, 2
• However, family history and race remain crucial for risk stratification and screening decisions 2