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. Newcomb & 6 others Noralane Lindor, John D. Potter, John A. Baron, Nathan Ellis, Trinidad Caldes, Xavier L. Lor

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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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DNA Mismatch Repair
MicroRNAs
Microsatellite Repeats
Colorectal Neoplasms
3' Untranslated Regions
Single Nucleotide Polymorphism
Alleles
Binding Sites
Genotype
Genes

ASJC Scopus subject areas

  • Cancer Research

Cite this

Association of a let-7 miRNA binding region of TGFBR1 with hereditary mismatch repair proficient colorectal cancer (MSS HNPCC). / Xicola, Rosa M.; Bontu, Sneha; Doyle, Brian J.; Rawson, Jamie; Garre, Pilar; Lee, Esther; De la Hoya, Miguel; Bessa, Xavier; Clofent, Joan; Bujanda, Luis; Balaguer, Francesc; Castellví-Bel, Sergi; Alenda, Cristina; Jover, Rodrigo; Ruiz-Ponte, Clara; Syngal, Sapna; Andreu, Montserrat; Carracedo, Angel; Castells, Antoni; Newcomb, Polly A.; Lindor, Noralane; Potter, John D.; Baron, John A.; Ellis, Nathan; Caldes, Trinidad; Lor, Xavier L.

In: Carcinogenesis, Vol. 37, No. 8, 01.08.2016, p. 751-758.

Research output: Contribution to journalArticle

Xicola, RM, Bontu, S, Doyle, BJ, 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, Newcomb, PA, Lindor, N, Potter, JD, Baron, JA, Ellis, N, Caldes, T & Lor, XL 2016, 'Association of a let-7 miRNA binding region of TGFBR1 with hereditary mismatch repair proficient colorectal cancer (MSS HNPCC)', Carcinogenesis, vol. 37, no. 8, pp. 751-758. https://doi.org/10.1093/carcin/bgw064
Xicola, Rosa M. ; Bontu, Sneha ; Doyle, Brian J. ; Rawson, Jamie ; Garre, Pilar ; Lee, Esther ; De la Hoya, Miguel ; Bessa, Xavier ; Clofent, Joan ; Bujanda, Luis ; Balaguer, Francesc ; Castellví-Bel, Sergi ; Alenda, Cristina ; Jover, Rodrigo ; Ruiz-Ponte, Clara ; Syngal, Sapna ; Andreu, Montserrat ; Carracedo, Angel ; Castells, Antoni ; Newcomb, Polly A. ; Lindor, Noralane ; Potter, John D. ; Baron, John A. ; Ellis, Nathan ; Caldes, Trinidad ; Lor, Xavier L. / Association of a let-7 miRNA binding region of TGFBR1 with hereditary mismatch repair proficient colorectal cancer (MSS HNPCC). In: Carcinogenesis. 2016 ; Vol. 37, No. 8. pp. 751-758.
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T1 - Association of a let-7 miRNA binding region of TGFBR1 with hereditary mismatch repair proficient colorectal cancer (MSS HNPCC)

AU - Xicola, Rosa M.

AU - Bontu, Sneha

AU - Doyle, Brian J.

AU - Rawson, Jamie

AU - Garre, Pilar

AU - Lee, Esther

AU - De la Hoya, Miguel

AU - Bessa, Xavier

AU - Clofent, Joan

AU - Bujanda, Luis

AU - Balaguer, Francesc

AU - Castellví-Bel, Sergi

AU - Alenda, Cristina

AU - Jover, Rodrigo

AU - Ruiz-Ponte, Clara

AU - Syngal, Sapna

AU - Andreu, Montserrat

AU - Carracedo, Angel

AU - Castells, Antoni

AU - Newcomb, Polly A.

AU - Lindor, Noralane

AU - Potter, John D.

AU - Baron, John A.

AU - Ellis, Nathan

AU - Caldes, Trinidad

AU - Lor, Xavier L.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

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DO - 10.1093/carcin/bgw064

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