PURPOSE: The clinical consequences of @entity14437 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the @entity5 risk faced by @entity14437 mutation carriers. METHODS: Data were collected from 98 @entity14437 families ascertained from family @entity5 clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate @entity14 ( @entity14 ) and @entity1204 ( @entity1204 ) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other @entity5 . RESULTS: The cumulative risk (CR) of @entity14 for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for @entity14 and 12% for @entity1204 . The mean age of @entity14 development was 52 years, and there was a significant difference in mean age of @entity14 between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a @entity14437 mutation (mean, 58 years; range, 31 to 86 years; P < .001). Significant SIRs were observed for @entity5 of the small bowel, ovaries, breast, and @entity8 . CONCLUSION: @entity14 and @entity1204 risks were found to be markedly lower than those previously reported for the other MMR. However, these risks embody the isolated risk of carrying a @entity14437 mutation, and it should be noted that we observed a substantial variation in @entity5 phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on @entity5 risks.

Lynch syndrome caused by germline XXXX mutations: delineating the @entity5 risk.

@entity1204 :: ('MESH:D016889', 'Disease') :: ['endometrial cancer', 'EC'] @entity8 :: ('MESH:D007674', 'Disease') :: ['renal pelvis'] @entity5 :: ('MESH:D009369', 'Disease') :: ['Lynch syndrome-associated cancers', 'cancers', 'cancer'] @entity14437 :: ('5395', 'Gene') :: ['PMS2'] @entity14 :: ('MESH:D015179', 'Disease') :: ['CRC', 'colorectal cancer']
@entity14437 :: (5395,Gene) :: ['PMS2']
