These authors have contributed equally to this work.
Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations
Article first published online: 13 JAN 2009
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard
Volume 75, Issue 2, pages 141–149, February 2009
How to Cite
Barrow, E., Robinson, L., Alduaij, W., Shenton, A., Clancy, T., Lalloo, F., Hill, J. and Evans, D. (2009), Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. Clinical Genetics, 75: 141–149. doi: 10.1111/j.1399-0004.2008.01125.x
Excerpts from this article were presented at The Association of Coloproctology of Great Britain and Ireland 2008 Annual Meeting on the 2 July 2008.
- Issue published online: 23 JAN 2009
- Article first published online: 13 JAN 2009
- Received 26 June 2008, revised and accepted for publication 6 October 2008
- DNA mismatch repair;
- hereditary non-polyposis colorectal cancer;
- Kaplan-Meiers analysis;
- Lynch syndrome;
- multiple primary neoplasms;
- statistical bias
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.