What is the strongest risk factor for prostate cancer?

Strongest Risk Factors for Prostate Cancer

The strongest risk factor for prostate cancer is a family history of prostate cancer, particularly having multiple first-degree relatives diagnosed with prostate cancer, which can increase risk up to 11-fold compared to men without family history. 1

Major Risk Factors by Strength of Association

Family History

• Having one first-degree relative (father, brother) with prostate cancer increases relative risk by 1.8 1
• Having a father and brother diagnosed with prostate cancer increases risk by 5.5-fold 1
• Having two brothers diagnosed with prostate cancer increases risk by 7.7-fold 1
• Men with three or more affected family members have an 11-fold increased risk 1
• Family history appears to be a stronger predictor than other demographic factors, with an odds ratio of 2.20 in some studies 1
• Approximately 9% of prostate malignancies are attributed to inherited predisposition 1

Genetic Mutations

• Carriers of BRCA2 mutations have significantly increased risk of prostate cancer 1
• Lynch syndrome (MSH2 and MSH6 mutations) is associated with increased prostate cancer risk 1
• BRCA1 mutations confer a lesser but still elevated risk 1
• True hereditary disease (three or more cases in same family, three successive generations, or two or more men diagnosed before age 55) is associated with onset 6-7 years earlier than non-hereditary cases 1

Age

• More than 70% of prostate cancer patients are older than 65 years at diagnosis 1
• Median age at diagnosis is 71 years; median age at death is 78 years 1
• More than 90% of deaths from prostate cancer occur in men older than 65 years 1
• A 50-year-old man has a 42% chance of developing histological evidence of prostate cancer during his lifetime 1

Race/Ethnicity

• African American men have a 64% higher incidence of prostate cancer compared to white men 1
• African American men have 2.3-fold higher prostate cancer mortality compared to white men 1
• African American men present with higher rates of high-grade prostatic intraepithelial neoplasia and higher Gleason scores 1
• Black race is associated with 20-96% increased odds of prostate cancer in various studies 1

Clinical Implications and Screening Recommendations

For Men with Family History

• Men with a strong family history should begin screening at age 40-45 2
• Family history is a stronger predictor of prostate cancer risk than race 3
• Early onset prostate cancer in the family (diagnosed before age 65) is a significant risk factor for first-degree relatives 4
• Men with a family history are significantly more likely to undergo biopsy, even when controlling for PSA and digital rectal examination findings 1

For Men with Genetic Mutations

• Consider germline testing for men with:
  • Metastatic prostate cancer who are candidates for targeted treatment 1
  • BRCA mutations on somatic testing 1
  • Multiple family members diagnosed with clinically significant prostate cancer before age 60 1
  • Family history of high-risk germline mutations or multiple cancers 1

For African American Men

• African American men represent a high-risk group requiring vigilant screening 1
• Current data are insufficient to inform the best screening strategy specifically for African American men 1
• Baseline PSA value is a stronger predictive factor than race alone 1, 3

Pitfalls in Risk Assessment

• Selection bias in studies may overestimate the association between family history and prostate cancer risk 5, 6
• Biopsy recommendation and acceptance rates differ by family history status, potentially inflating risk estimates 1
• The true association between risk factors and prostate cancer may be overestimated in the absence of study-mandated biopsies 1
• Screening recommendations should account for both the increased risk and the potential for overdiagnosis in high-risk populations 1