Association of a let-7 miRNA binding region of TGFBR1 with hereditary mismatch repair proficient colorectal cancer (MSS HNPCC)

Rosa M. Xicola, Sneha Bontu, Brian J. Doyle, Jamie Rawson, Pilar Garre, Esther Lee, Miguel De la Hoya, Xavier Bessa, Joan Clofent, Luis Bujanda, Francesc Balaguer, Sergi Castellví-Bel, Cristina Alenda, Rodrigo Jover, Clara Ruiz-Ponte, Sapna Syngal, Montserrat Andreu, Angel Carracedo, Antoni Castells, Polly A. NewcombNoralane Lindor, John D. Potter, John A. Baron, Nathan A. Ellis, Trinidad Caldes, Xavier L. Lor

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8 Scopus citations

Abstract

The purpose of this study was to identify novel colorectal cancer (CRC)-causing alleles in unexplained familial CRC cases. In order to do so, coding regions in five candidate genes (MGMT, AXIN2, CTNNB1, TGFBR1 and TGFBR2) were sequenced in 11 unrelated microsatellite-stable hereditary non-polyposis CRC (MSS HNPCC) cases. Selected genetic variants were genotyped in a discovery set of 27 MSS HNPCC cases and 85 controls. One genetic variant, rs67687202, in TGFBR1 emerged as significant (P = 0.002), and it was genotyped in a replication set of 87 additional MSS HNPCC-like cases and 338 controls where it was also significantly associated with MSS HNPCC cases (P = 0.041). In the combined genotype data, rs67687202 was associated with a moderate increase in CRC risk (OR = 1.68; 95% CI = 1.13-2.50; P = 0.010). We tested a highly correlated SNP rs868 in 723 non-familial CRC cases compared with 629 controls, and it was not significantly associated with CRC risk (P = 0.370). rs868 is contained in a let-7 miRNA binding site in the 3'UTR of TGFBR1, which might provide a functional basis for the association.

Original languageEnglish (US)
Pages (from-to)751-758
Number of pages8
JournalCarcinogenesis
Volume37
Issue number8
DOIs
StatePublished - Aug 1 2016

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ASJC Scopus subject areas

  • Cancer Research

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Xicola, R. M., Bontu, S., Doyle, B. J., Rawson, J., Garre, P., Lee, E., De la Hoya, M., Bessa, X., Clofent, J., Bujanda, L., Balaguer, F., Castellví-Bel, S., Alenda, C., Jover, R., Ruiz-Ponte, C., Syngal, S., Andreu, M., Carracedo, A., Castells, A., ... Lor, X. L. (2016). Association of a let-7 miRNA binding region of TGFBR1 with hereditary mismatch repair proficient colorectal cancer (MSS HNPCC). Carcinogenesis, 37(8), 751-758. https://doi.org/10.1093/carcin/bgw064