JAMA<\/a>, showed that pathogenic or likely pathogenic variants (P\/LPVs) for cancer susceptibility genes were much more common than previously thought.<\/p>\nThe findings suggest that the typical practice of reserving germline genetic testing for cancer susceptibility among people with known risk factors will not identify all at-risk individuals.<\/p>\n
This could lead to missed opportunities for personalized screening and surveillance.<\/p>\n
The researchers also noted that prior research has shown that structured clinical management for patients with pathogenic variants is both cost-effective and lifesaving.<\/p>\n
\u201cAlthough this evidence does not support additional screening, future studies should evaluate the clinical utility, cost-effectiveness, and feasibility of broader genetic screening,\u201d recommended Gideon Idumah, PhD, from the Cleveland Clinic in Ohio, and co-workers.<\/p>\n
Most prior research has focused on the prevalence of P\/LPVs in patients with cancer and less is known about their frequency in large, unselected populations.<\/p>\n
To investigate further, the team set out to estimate the population-level prevalence of pathogenic variants in key cancer susceptibility genes among 414,830 participants in the All of Us study, a major U.S. initiative funded by the National Institutes of Health to further precision medicine.<\/p>\n
Data from short-read whole genome sequencing and demographic data such as sex and ethnicity were analyzed.<\/p>\n
The researchers identified 3454 unique P\/LPVs across 77 transcripts and 72 genes, in 20,968 unique individuals, representing approximately 5.05% of the total population. Among these individuals, 469 had variants in more than one gene.<\/p>\n
The prevalence of pathogenic variants did not differ according to sex, the authors report.<\/p>\n
However, there were significant differences across racial groups, with Asian participants having the lowest prevalence and White participants the highest at 5.72%.<\/p>\n
Of the individual genes, MUTYH had the highest prevalence at 1.33%, followed by BRCA2 at 0.42%, and MITF at 0.37%.<\/p>\n
Twelve genes significantly differed in prevalence depending on whether the participant was Hispanic.<\/p>\n
Overall, racial differences were observed in 18 genes with MUTYH showing the greatest variability.<\/p>\n
The researchers note that people who are heterozygous for the autosomal recessive genes MUTYH, NBN, BLM, WRN, MSH3, DIS3L2, and RAD50 have no known increased risk for cancer, albeit carrying a reproductive risk.<\/p>\n
The analysis also showed that 8932 participants have an autosomal recessive condition. In addition, 450 participants had possible mosaic P\/LPVs, using a threshold of variant allele frequency of less than 30%.<\/p>\n
There were significant differences between carriers and noncarriers in the prevalence of cancer, age at first cancer diagnosis, and in the number of family members with a history of cancer diagnosis.<\/p>\n
In terms of the age at which cancer was first diagnosed, STK11 carriers and DICER1 carriers had the lowest median age, at a corresponding 31.4 and 35.4 years, while AIP carriers the highest at 70.8 years.<\/p>\n
The carrier frequencies for BRCA1 and BRCA2 were 0.22% and 0.42%, respectively, which was far higher than previous estimates for non-Ashkenazi Jewish populations of between 0.13% and 0.25%.<\/p>\n
The researchers note that a previous study suggested rates of thyroid cancer\u2013associated variants approximately 10 to 20 times higher than current population estimates.<\/p>\n
\u201cCombined, these findings suggest that current genetic testing guidelines may not identify all at-risk individuals, although the clinical impact of broadening screening has not been evaluated,\u201d the team wrote.<\/p>\n","protected":false},"excerpt":{"rendered":"Credit: frimages\/Getty Images One in every 20 people may inherit a genetic variant in key genes that make…\n","protected":false},"author":2,"featured_media":83935,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25],"tags":[5989,63590,19159,2484,405,111,2479,139,69,2478,147,2477,15284],"class_list":{"0":"post-83934","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-cancer-screening","9":"tag-cancers","10":"tag-genetic-testing-diagnostic-technique","11":"tag-genetic-variants","12":"tag-genetics","13":"tag-new-zealand","14":"tag-news-features","15":"tag-newzealand","16":"tag-nz","17":"tag-precision-medicine","18":"tag-science","19":"tag-topics","20":"tag-whole-genome-sequencing"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/83934","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=83934"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/83934\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/83935"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=83934"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=83934"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=83934"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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Credit: frimages\/Getty Images<\/p>\n