The MLH1c.1852-1853delinsGC (p.K618A) variant in colorectal cancer: Genetic association study in 18,723 individuals

Anna Abulí, Luis Bujanda, Jenifer Muñoz, Stephan Buch, Clemens Schafmayer Maria Valeria Maiorana, Silvia Veneroni, Tom Van Wezel, Tao Liu, Helga Westers, Clara Esteban-Jurado, Teresa Ocaña, Josep M. Piqué, Montserrat Andreu, Rodrigo Jover, Angel Carracedo, Rosa M. Xicola, Xavier Llor, Antoni Castells, Malcolm Dunlop, Robert HofstraAnnika Lindblom, Juul Wijnen, Paolo Peterlongo, Jochen Hampe, Clara Ruiz-Ponte, Sergi Castellví-Bel

Research output: Contribution to journalArticle


Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance", being the c.1852-1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

Original languageEnglish
Article numbere95022
JournalPLoS One
Issue number4
Publication statusPublished - Apr 17 2014


ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Abulí, A., Bujanda, L., Muñoz, J., Buch, S., Maiorana, C. S. M. V., Veneroni, S., Van Wezel, T., Liu, T., Westers, H., Esteban-Jurado, C., Ocaña, T., Piqué, J. M., Andreu, M., Jover, R., Carracedo, A., Xicola, R. M., Llor, X., Castells, A., Dunlop, M., ... Castellví-Bel, S. (2014). The MLH1c.1852-1853delinsGC (p.K618A) variant in colorectal cancer: Genetic association study in 18,723 individuals. PLoS One, 9(4), [e95022].