Risk of multiple colorectal cancer development depends on age and subgroup in individuals with hereditary predisposition
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Development of multiple colorectal cancers (CRCs), synchronously or metachronously, is associated with hereditary predisposition for cancer and accurate risk estimates of multiple tumour development are relevant to recommend rational surveillance programs. A cross-sectional study design was used to estimate the risks of synchronous CRC (SCRC) and metachronous CRC (MCRC) based on data from the National Danish Hereditary Nonpolyposis Register. In total, 7100 individuals from families within the subgroups Lynch syndrome, familial CRC (FCC) and moderate risk were used with estimates relative to a non-hereditary population control cohort. SCRC was diagnosed in 7.4% of the Lynch syndrome cases, in 4.2% of FCC cases and 2.5% of the moderate risk cases, which translated to relative risks of 1.9–5.6. The risk of MCRC was distinctively linked to Lynch syndrome with a life-time risk up to 70% and an incidence rate ratio of 5.0. The risk of SCRC was significantly increased in all subgroups of FCC and hereditary CRC, whereas the risk of MCRC was specifically linked to Lynch syndrome. These observations suggest that individuals with FCC or hereditary CRC should be carefully screened for second primary CRC at the time of diagnosis, whereas intensified surveillance for second primary CRC is motivated in Lynch syndrome with lower-intensity programs in families with yet unidentified genetic causes.
KeywordsHNPCC Lynch syndrome Colonoscopy Cross-sectional study Metachronous neoplasms Synchronous neoplasms Multiple primary neoplasms
Financial support was granted from the Danish Cancer Society (Grant No. R90-A6150) and from the Swedish Cancer Society (Grant No. 2014/442). We would also like to thank all clinicians who have contributed with data to the Danish HNPCC Register.
- 12.Hu H, Chang DT, Nikiforova MN et al (2013) Clinicopathologic features of synchronous colorectal carcinoma: a distinct subset arising from multiple sessile serrated adenomas and associated with high levels of microsatellite instability and favorable prognosis. Am J Surg Pathol 37:1660–1670. https://doi.org/10.1097/PAS.0b013e31829623b8 CrossRefPubMedGoogle Scholar
- 15.Fante R, Roncucci L, Di Gregorio C et al (1996) Frequency and clinical features of multiple tumors of the large bowel in the general population and in patients with hereditary colorectal carcinoma. Cancer 77:2013–2021. https://doi.org/10.1002/(SICI)1097-0142(19960515)77:10%3C2013::AID-CNCR8%3E3.0.CO;2-R CrossRefPubMedGoogle Scholar
- 19.Møller P, Seppälä T, Bernstein I et al (2017) Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database. Gut 66:1657–1664. https://doi.org/10.1136/gutjnl-2016-311403 CrossRefPubMedGoogle Scholar
- 22.Vasen HFA, Watson P, Mecklin J, Lynch HT (1999) New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 116:1453–1456. https://doi.org/10.1016/S0016-5085(99)70510-X CrossRefPubMedGoogle Scholar
- 24.R Core Team (2017) R: a language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
- 34.Zauber P, Huang J, Sabbath-Solitare M, Marotta S (2013) Similarities of molecular genetic changes in synchronous and metachronous colorectal cancers are limited and related to the cancers’ proximities to each other. J Mol Diagn 15:652–660. https://doi.org/10.1016/j.jmoldx.2013.03.009 CrossRefPubMedGoogle Scholar