Men may be slipping through the cracks in cancer prevention, as new research shows they are far less likely to undergo genetic testing despite being more likely to carry high-risk cancer variants when they do.
Study: Testing for hereditary cancer genes in men: a missed opportunity for cancer prevention. Image credit: Pixel-Shot/Shutterstock.com
A study published in Frontiers in Oncology found that fewer men undergo genetic testing for hereditary cancer syndromes compared to women, but are more likely to test positive. This may indicate a potential gap in cancer risk surveillance and prediction.
Genetic testing reveals inherited cancer risks, but often misses men
Genetic testing for inherited cancer syndromes is an important tool to identify genetic cancer risks. At-risk patients can be monitored, their relatives screened, and early intervention offered wherever appropriate.
Women have benefited from genetic testing. Professional medical associations and organizations recommend that primary care providers assess all women for hereditary breast and ovarian cancer risk factors, including personal or family history of cancer, or Ashkenazi Jewish ancestry. These women may then be offered genetic testing for hereditary breast and ovarian cancer syndromes linked to the presence of BRCA variants.
Similar protocols have been established for other inherited cancer syndromes in women, including Lynch syndrome. Clinical protocols have also been published for men with BRCA1/2 variants, and the researchers recommended regular screening and intervention, as well as familial risk education, to identify more men with such variants.
However, there is a lack of published studies on hereditary cancer testing in men. This limits current understanding of men's uptake of hereditary cancer testing and of what predicts higher uptake. The current study sought to fill this gap, in view of the higher cancer-related morbidity and mortality rates in men compared to women.
Comparing testing patterns by sex
The researchers conducted a retrospective study of laboratory cancer testing data from adults collected between June 2020 and August 2023. This compared testing in men and women.
The study included assessment of demographic details, personal and family history of cancer, gene panel size, test results, and the proportion of tests that identified variants for which clinical actions such as surveillance or intervention have been recommended.
Gene panel size was stratified as small (<20 genes), medium (20–53 genes), and large (>53 genes).
Men make up just five percent of tests
The study analyzed data from 224,041 individuals, of whom only 5 % were men, highlighting a gender imbalance in genetic testing uptake. Men were also older at the time of testing, with an average age of 54 years compared to 43 years in women. Among participants with available ethnicity data, 47 % were White, while Hispanic and Black individuals accounted for 14 % and 13 %, respectively.
Clear differences emerged in how and why men and women underwent testing. Men were more likely to be of Ashkenazi Jewish ancestry and were seven times more likely than women to be tested through cascade testing after a pathogenic variant had been identified in a relative. At the same time, men were significantly more likely to have a personal history of cancer (27 % vs 13 %), but less likely to report a family history of cancer, with missing family history data also more common among men.
Referral pathways also differed by sex. Men were typically referred through primary care or general specialty clinics, such as internal or family medicine, whereas women were more often referred through women’s health services. In addition, men were more likely to receive larger or custom gene panels, at rates three to four times higher than those seen in women.
Despite being tested less often, men were more likely to receive clinically significant results. The positivity rate for pathogenic or likely pathogenic variants was 14 % in men, compared to 8 % in women, which is notably higher than the approximately 5 % rate reported in unselected populations. Among individuals with such variants and available clinical data, 35.1 % of men and 19.3 % of women reported a personal history of cancer.
The types of cancers observed in men also showed distinct patterns. Among those with a personal cancer history, prostate, colorectal, and pancreatic cancers were the most commonly reported. However, pathogenic variants were most strongly associated with lung, stomach, colorectal, and multiple cancers in men.
Men were also more likely to carry actionable variants, particularly in BRCA1/2 genes, which were identified three times more frequently in men than in women. Together, these findings suggest that men may be undergoing testing later in the disease course, potentially after cancer has already developed, rather than as part of preventive risk assessment.
Men are often tested only after a cancer diagnosis
The authors propose several reasons for this disparity. Men may be referred for testing primarily after a cancer diagnosis, often to guide treatment decisions or confirm tumor-related findings. More broadly, lower engagement with preventive healthcare, reduced health-seeking behavior, and lower referral rates may all contribute to the underutilization of genetic testing in men. Hesitancy to pursue testing without a clear or immediate risk, along with the lack of male-specific screening guidelines, may further limit uptake.
These challenges are compounded by limitations in current risk assessment tools. Existing BRCA-related prediction models are largely designed for women and may not accurately identify men who would benefit from testing, particularly those with prostate cancer. In addition, men with pathogenic BRCA1/2 variants are less likely to undergo genetic counseling, despite the implications not only for their own cancer risk but also for their relatives, including daughters at risk of breast and ovarian cancer.
Improve male-focused cancer risk prediction tools
The authors suggest four courses of action: improving research to better document and understand family cancer history among men, optimizing male-focused hereditary cancer risk prediction tools, identifying and addressing the reasons for low uptake of genetic counseling and preventive care, and integrating hereditary cancer screening more fully into routine healthcare for men, particularly in primary care settings.
Strengths and limitations
This study used a large patient sample from across the US, including many individuals without a personal history of cancer, most of whom tested negative. However, it had some limitations:
Reliance on patient- or provider-reported family cancer history may introduce recall bias, as well as an older average age for men compared to women, which could contribute to selection bias.
In addition, most tests were ordered through women’s health or obstetrics/gynecology clinics, and using data from a single laboratory may exclude individuals tested elsewhere. The retrospective design using data from a single commercial laboratory may also limit generalizability to the broader population, and there may be potential conflicts of interest, as several authors are affiliated with the laboratory that provided the data.
Closing testing gaps could improve cancer outcomes
While men were less likely to undergo genetic testing for hereditary cancers, compared to women, they were more likely to test positive when tested. Future research should establish the barriers to testing in men. In addition, healthcare professionals should be made aware of the need for such screening to ensure better cancer outcomes for these patients and their families.
These findings underscore the need for greater integration of routine screening for hereditary cancer risk factors for men in primary care settings.
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