Men Less Likely to Undergo Genetic Testing for Cancer Risk, Yet Show Higher Positivity Rates

New research indicates a significant disparity in genetic testing for hereditary cancer syndromes: men are less likely than women to undergo testing, despite showing a higher likelihood of testing positive for high-risk cancer variants when tested. This study suggests a potential gap in cancer risk surveillance and prediction for men.

The research, published in Frontiers in Oncology, provides a retrospective analysis of laboratory cancer testing data. It encompassed 224,041 adults and was collected between June 2020 and August 2023.

Key Study Findings

The analysis revealed several critical differences between men and women in genetic testing patterns:

• Participation Imbalance: Men constituted a mere 5% of the total individuals tested.
• Age at Testing: Men were significantly older at the time of testing, with an average age of 54 years compared to 43 years for women.
• Referral Patterns: Men were seven times more likely to undergo cascade testing (testing based on a relative's positive result). They also reported a personal history of cancer more frequently (27% vs. 13% in women) but were less likely to report a family history of cancer.
• Testing Pathways: Men were typically referred for testing through primary care or general specialty clinics, whereas women were more often referred via women’s health services.
• Positivity Rate: The positivity rate for pathogenic or likely pathogenic variants was notably higher in men, at 14%, compared to 8% in women.
• Variant Types: Men were more likely to carry actionable variants, particularly in BRCA1/2 genes, which were identified three times more frequently than in women.
• Cancer Types: Among men with a personal cancer history, prostate, colorectal, and pancreatic cancers were the most commonly reported.

These findings strongly suggest that men may be undergoing genetic testing later in life, potentially after a cancer diagnosis has already occurred, rather than as part of proactive, preventive risk assessment.

Potential Reasons for the Disparity

The authors propose several factors contributing to this notable disparity in genetic testing for hereditary cancer syndromes:

• Diagnostic-Driven Testing: Men may be referred for testing primarily after a cancer diagnosis, often to guide treatment decisions rather than for preventive purposes.
• Lower Engagement with Preventive Care: A general trend of lower engagement with preventive healthcare and reduced health-seeking behavior in men may play a role.
• Lack of Male-Specific Guidelines: The absence of dedicated male-specific screening guidelines for hereditary cancers could be a contributing factor.
• Female-Centric Prediction Models: Current BRCA-related prediction models are largely designed for women and may not accurately identify at-risk men.
• Reduced Genetic Counseling Uptake: Men with pathogenic BRCA1/2 variants are less likely to undergo genetic counseling, a crucial step in understanding and managing risk.

Recommendations for Action

To address this significant gap and enhance cancer risk surveillance for men, the authors recommend several key actions:

• Improve Family History Documentation: Conduct more research to better document family cancer history among men.
• Optimize Male-Focused Risk Tools: Develop and refine hereditary cancer risk prediction tools specifically tailored for men.
• Address Barriers to Care: Identify and actively address the barriers that hinder men's uptake of genetic counseling and preventive care.
• Integrate Screening into Routine Care: More fully integrate hereditary cancer screening into routine healthcare for men, especially within primary care settings.

Study Limitations

It is important to acknowledge the limitations of this study:

• Recall Bias: Potential recall bias may exist due to patient- or provider-reported family cancer history.
• Selection Bias (Age): An older average age for men in the study could have introduced selection bias.
• Generalizability: Reliance on data from a single commercial laboratory may limit the generalizability of the findings to broader populations.
• Affiliations: Several authors are affiliated with the laboratory that provided the study data.