Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study.

Win A. K., Dowty J. G., Reece J. C., Lee G., Templeton A. S., Plazzer J., ...More

The Lancet. Oncology, vol.22, pp.1014-1022, 2021 (SCI-Expanded) identifier identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 22
  • Publication Date: 2021
  • Doi Number: 10.1016/s1470-2045(21)00189-3
  • Journal Name: The Lancet. Oncology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, CINAHL, EMBASE, MEDLINE
  • Page Numbers: pp.1014-1022
  • Bursa Uludag University Affiliated: Yes


Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (p 0 center dot 0001 for each of the three three continents). These familial risk factors resulted in a wide within-gene variation in the risk of colorectal cancer for men and women from each continent who all carried pathogenic variants in the same gene or the MSH2 c.942+3A T variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and only