Journal: Scientific reports
This study characterizes the TP53 variant p.R181H within a Swedish Li-Fraumeni Syndrome (LFS) cohort, revealing it as a potential founder mutation present in 22% of families, significantly higher than in other populations.
Carriers of p.R181H exhibited lower cancer incidence and better survival compared to other TP53 mutation carriers.
Cancer manifestation was sex-specific:
- Females primarily developed breast cancer from around age 29.
- Males predominantly developed prostate cancer from age 45.
- No cancers were detected in children.
Tumor analyses confirmed loss of heterozygosity, and haplotype data estimated the variant’s origin at approximately 550 years ago.
These findings suggest surveillance for p.R181H carriers could be tailored to adult screening focused on breast and prostate cancer, potentially excluding pediatric surveillance.
Validation in additional cohorts is recommended.