TY - JOUR
T1 - Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer
T2 - a report from the prospective Lynch syndrome database
AU - Møller, Pål
AU - Seppälä, Toni
AU - Bernstein, Inge
AU - Holinski-Feder, Elke
AU - Sala, Paola
AU - Evans, D Gareth
AU - Lindblom, Annika
AU - Macrae, Finlay
AU - Blanco, Ignacio
AU - Sijmons, Rolf
AU - Jeffries, Jacqueline
AU - Vasen, Hans
AU - Burn, John
AU - Nakken, Sigve
AU - Hovig, Eivind
AU - Rødland, Einar Andreas
AU - Tharmaratnam, Kukatharmini
AU - de Vos Tot Nederveen Cappel, Wouter H
AU - Hill, James
AU - Wijnen, Juul
AU - Jenkins, Mark
AU - Green, Kate
AU - Lalloo, Fiona
AU - Sunde, Lone
AU - Mints, Miriam
AU - Bertario, Lucio
AU - Pineda, Marta
AU - Navarro, Matilde
AU - Morak, Monika
AU - Renkonen-Sinisalo, Laura
AU - Frayling, Ian M
AU - Plazzer, John-Paul
AU - Pylvanainen, Kirsi
AU - Genuardi, Maurizio
AU - Mecklin, Jukka-Pekka
AU - Möslein, Gabriela
AU - Sampson, Julian R
AU - Capella, Gabriel
AU - Mallorca Group (http://mallorca-group.org)
N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
U2 - 10.1136/gutjnl-2016-311403
DO - 10.1136/gutjnl-2016-311403
M3 - Journal article
C2 - 27261338
SN - 0017-5749
VL - 66
SP - 1657
EP - 1664
JO - Gut
JF - Gut
IS - 9
ER -