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Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations.
Clin Genet 2009; 75(2):141-9CG

Abstract

Lynch syndrome or hereditary non-polyposis colorectal cancer is caused by mutations of DNA mismatch repair (MMR) genes. The extracolonic tumour spectrum includes endometrial, ovarian, gastric, small bowel, pancreatic, hepatobiliary, brain, and urothelial neoplasms. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with a Lynch syndrome spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. Kaplan-Meier analysis of risk to 70 years was calculated. One hundred and eighty-four Lynch syndrome spectrum extracolonic cancers in 839 proven, obligate, or assumed mutation carriers were analysed. Cumulative risk for females of an extracolonic tumour is 47.4% (95% CI 43.9-50.8). The risk to males is 26.5% (95% CI 22.6-30.4). There was no reduction in gynaecological malignancies due to gynaecological screening (examination, transvaginal ultrasound scan, hysteroscopy and endometrial biopsy). Males have a higher risk of gastric cancer than females (p = 0.0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic.

Authors+Show Affiliations

Department of General Surgery, Manchester Royal Infirmary, Manchester, UK. emma.barrow@doctors.org.uk

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

19215248

Citation

Barrow, E, et al. "Cumulative Lifetime Incidence of Extracolonic Cancers in Lynch Syndrome: a Report of 121 Families With Proven Mutations." Clinical Genetics, vol. 75, no. 2, 2009, pp. 141-9.
Barrow E, Robinson L, Alduaij W, et al. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. Clin Genet. 2009;75(2):141-9.
Barrow, E., Robinson, L., Alduaij, W., Shenton, A., Clancy, T., Lalloo, F., ... Evans, D. G. (2009). Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. Clinical Genetics, 75(2), pp. 141-9. doi:10.1111/j.1399-0004.2008.01125.x.
Barrow E, et al. Cumulative Lifetime Incidence of Extracolonic Cancers in Lynch Syndrome: a Report of 121 Families With Proven Mutations. Clin Genet. 2009;75(2):141-9. PubMed PMID: 19215248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. AU - Barrow,E, AU - Robinson,L, AU - Alduaij,W, AU - Shenton,A, AU - Clancy,T, AU - Lalloo,F, AU - Hill,J, AU - Evans,D G, PY - 2009/2/14/entrez PY - 2009/2/14/pubmed PY - 2009/4/17/medline SP - 141 EP - 9 JF - Clinical genetics JO - Clin. Genet. VL - 75 IS - 2 N2 - Lynch syndrome or hereditary non-polyposis colorectal cancer is caused by mutations of DNA mismatch repair (MMR) genes. The extracolonic tumour spectrum includes endometrial, ovarian, gastric, small bowel, pancreatic, hepatobiliary, brain, and urothelial neoplasms. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with a Lynch syndrome spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. Kaplan-Meier analysis of risk to 70 years was calculated. One hundred and eighty-four Lynch syndrome spectrum extracolonic cancers in 839 proven, obligate, or assumed mutation carriers were analysed. Cumulative risk for females of an extracolonic tumour is 47.4% (95% CI 43.9-50.8). The risk to males is 26.5% (95% CI 22.6-30.4). There was no reduction in gynaecological malignancies due to gynaecological screening (examination, transvaginal ultrasound scan, hysteroscopy and endometrial biopsy). Males have a higher risk of gastric cancer than females (p = 0.0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic. SN - 1399-0004 UR - https://www.unboundmedicine.com/medline/citation/19215248/Cumulative_lifetime_incidence_of_extracolonic_cancers_in_Lynch_syndrome:_a_report_of_121_families_with_proven_mutations_ L2 - https://doi.org/10.1111/j.1399-0004.2008.01125.x DB - PRIME DP - Unbound Medicine ER -