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Lynch Syndrome Caused by Germline PMS2 Mutations:Delineating the Cancer Risk
- Source :
- Ten Broeke, S W, Brohet, R M, Tops, C M, van der Klift, H M, Velthuizen, M E, Bernstein, I, Capellá Munar, G, Gomez Garcia, E, Hoogerbrugge, N, Letteboer, T G W, Menko, F H, Lindblom, A, Mensenkamp, A R, Moller, P, van Os, T A, Rahner, N, Redeker, B J W, Sijmons, R H, Spruijt, L, Suerink, M, Vos, Y J, Wagner, A, Hes, F J, Vasen, H F, Nielsen, M & Wijnen, J T 2015, ' Lynch Syndrome Caused by Germline PMS2 Mutations : Delineating the Cancer Risk ', Journal of Clinical Oncology, vol. 33, no. 4, pp. 319-325 . https://doi.org/10.1200/JCO.2014.57.8088, Journal of Clinical Oncology, 33(4), 319-U172. American Society of Clinical Oncology, Journal of Clinical Oncology, 33, 319-25, ten Broeke, S W, Brohet, R M, Tops, C M, van der Klift, H M, Velthuizen, M E, Bernstein, I, Munar, G C, Garcia, E G, Hoogerbrugge, N, Letteboer, T G W, Menko, F H, Lindblom, A, Mensenkamp, A R, Moller, P, Os, T A, Rahner, N, Redeker, B J W, Sijmons, R H, Spruijt, L, Suerink, M, Vos, Y J, Wagner, A, Hes, F J, Vasen, HF, Nielsen, M & Wijnen, J T 2015, ' Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk ', Journal of Clinical Oncology, vol. 33, no. 4, pp. 319-325 . https://doi.org/10.1200/JCO.2014.57.8088, Journal of Clinical Oncology, 33(4), 319-U172, Journal of Clinical Oncology, 33, 4, pp. 319-25, Journal of clinical oncology, 33(4), 319-U172. American Society of Clinical Oncology, Journal of Clinical Oncology, 33(4), 319-325. AMER SOC CLINICAL ONCOLOGY, Journal of Clinical Oncology, 33(4), 319-325. American Society of Clinical Oncology
- Publication Year :
- 2015
-
Abstract
- Purpose The clinical consequences of PMS2 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 cancer risk faced by PMS2 mutation carriers. Methods Data were collected from 98 PMS2 families ascertained from family cancer 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 colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome–associated cancers. Results The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P < .001). Significant SIRs were observed for cancers of the small bowel, ovaries, breast, and renal pelvis. Conclusion CRC and EC 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 PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks.
- Subjects :
- Oncology
Male
Cancer Research
Colorectal cancer
DNA Mutational Analysis
VARIANTS
GUIDELINES
FAMILIES
Cohort Studies
Gene Frequency
Risk Factors
PMS2
Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14]
CRITERIA
Mismatch Repair Endonuclease PMS2
Genetics
Medicine(all)
Adenosine Triphosphatases
Aged, 80 and over
Adenosine Triphosphatases/genetics
Genetic Predisposition to Disease/genetics
COLON-CANCER
MLH1
NONPOLYPOSIS COLORECTAL-CANCER
Middle Aged
DNA Repair Enzymes/genetics
CARRIERS
Lynch syndrome
DNA-Binding Proteins
Female
Colorectal Neoplasms
Cohort study
Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Adult
medicine.medical_specialty
congenital, hereditary, and neonatal diseases and abnormalities
Genotype
Germline mutation
SDG 3 - Good Health and Well-being
Internal medicine
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
SURVEILLANCE
medicine
Humans
Genetic Predisposition to Disease
Germ-Line Mutation
Aged
Family Health
business.industry
Endometrial cancer
Cancer
medicine.disease
Colorectal Neoplasms/genetics
Colorectal Neoplasms, Hereditary Nonpolyposis
digestive system diseases
Endometrial Neoplasms
DNA Repair Enzymes
CLINICAL MANAGEMENT
business
Endometrial Neoplasms/genetics
DNA-Binding Proteins/genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0732183X
- Database :
- OpenAIRE
- Journal :
- Ten Broeke, S W, Brohet, R M, Tops, C M, van der Klift, H M, Velthuizen, M E, Bernstein, I, Capellá Munar, G, Gomez Garcia, E, Hoogerbrugge, N, Letteboer, T G W, Menko, F H, Lindblom, A, Mensenkamp, A R, Moller, P, van Os, T A, Rahner, N, Redeker, B J W, Sijmons, R H, Spruijt, L, Suerink, M, Vos, Y J, Wagner, A, Hes, F J, Vasen, H F, Nielsen, M & Wijnen, J T 2015, ' Lynch Syndrome Caused by Germline PMS2 Mutations : Delineating the Cancer Risk ', Journal of Clinical Oncology, vol. 33, no. 4, pp. 319-325 . https://doi.org/10.1200/JCO.2014.57.8088, Journal of Clinical Oncology, 33(4), 319-U172. American Society of Clinical Oncology, Journal of Clinical Oncology, 33, 319-25, ten Broeke, S W, Brohet, R M, Tops, C M, van der Klift, H M, Velthuizen, M E, Bernstein, I, Munar, G C, Garcia, E G, Hoogerbrugge, N, Letteboer, T G W, Menko, F H, Lindblom, A, Mensenkamp, A R, Moller, P, Os, T A, Rahner, N, Redeker, B J W, Sijmons, R H, Spruijt, L, Suerink, M, Vos, Y J, Wagner, A, Hes, F J, Vasen, HF, Nielsen, M & Wijnen, J T 2015, ' Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk ', Journal of Clinical Oncology, vol. 33, no. 4, pp. 319-325 . https://doi.org/10.1200/JCO.2014.57.8088, Journal of Clinical Oncology, 33(4), 319-U172, Journal of Clinical Oncology, 33, 4, pp. 319-25, Journal of clinical oncology, 33(4), 319-U172. American Society of Clinical Oncology, Journal of Clinical Oncology, 33(4), 319-325. AMER SOC CLINICAL ONCOLOGY, Journal of Clinical Oncology, 33(4), 319-325. American Society of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....d91095fdf504e9f316e72f7ed8460fd2