Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer

Objective Today most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do subsequent cancers occur; and (iii) what is the survival following these cancers? Design Information was collated on prospectively organised surveillance and prospectively observed outcomes in patients with LS who had cancer prior to inclusion and analysed by age, gender and genetic variants. Results 1273 patients with LS from 10 countries were followed up for 7753 observation years. 318 patients (25.7%) developed 341 first subsequent cancers, including colorectal (n=147, 43%), upper GI, pancreas or bile duct (n=37, 11%) and urinary tract (n=32, 10%). The cumulative incidences for any subsequent cancer from age 40 to age 70 years were 73% for pathogenic MLH1 (path_MLH1), 76% for path_MSH2 carriers and 52% for path_MSH6 carriers, and for colorectal cancer (CRC) the cumulative incidences were 46%, 48% and 23%, respectively. Crude survival after any subsequent cancer was 82% (95% CI 76% to 87%) and 10-year crude survival after CRC was 91% (95% CI 83% to 95%). Conclusions Relative incidence of subsequent cancer compared with incidence of first cancer was slightly but insignificantly higher than cancer incidence in patients with LS without previous cancer (range 0.94–1.49). The favourable survival after subsequent cancers validated continued follow-up to prevent death from cancer. The interactive website http://lscarisk.org was expanded to calculate the risks by gender, genetic variant and age for subsequent cancer for any patient with LS with previous cancer. INTRODUCTION Lynch syndrome (LS) is associated with a high probability of GI, gynaecological and other cancers. 2 It is caused by germline pathogenic variants in any of the four DNA mismatch repair Significance of this study What is already known on this subject? ▸ Inherited colorectal cancer may be caused by mismatch repair (MMR) gene variants and is then commonly referred to as Lynch syndrome. ▸ Patients with Lynch syndrome are at risk for synchronous and metachronous cancers. ▸ Endoscopic surveillance with removal of adenomas is recommended to prevent colorectal cancer. What are the new findings? ▸ This is the first comprehensive prospective study to provide empirically observed data on subsequent cancer incidence and survival in patients with Lynch syndrome who have survived previous cancer. ▸ The cumulative incidences for any subsequent cancer were 73% for path_MLH1 and 76% for path_MSH2 carriers. The incidence was lower in MSH6 carriers. ▸ Colorectal cancer occurred frequently despite continued colonoscopic surveillance with removal of adenomas. ▸ Survival after subsequent cancer was good. 1657 Møller P, et al. Gut 2017;66:1657–1664. doi:10.1136/gutjnl-2016-311403 Colon To cite: Møller P, Seppälä T, Bernstein I, et al. Gut 2017;66:1657–1664. ► Additional material is published online only. To view please visit the journal online (http:// dx. doi. org/ 10. 1136/ gutjnl2016311403). For numbered affiliations see end of article. Correspondence to Dr Pål Møller, Research Group Inherited Cancer, The Norwegian Radium Hospital, Oslo 0310, Norway; moller. pal@ gmail. com Received 4 January 2016 Revised 6 May 2016 Accepted 10 May 2016 Published Online First 3 June 2016 group.bmj.com on September 7, 2017 Published by http://gut.bmj.com/ Downloaded from