التفاصيل البيبلوغرافية
| العنوان: |
Association of a let-7 miRNA binding region of TGFBR1 with hereditary mismatch repair proficient colorectal cancer (MSS HNPCC). |
| المؤلفون: |
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. |
| المصدر: |
Carcinogenesis; Aug2016, Vol. 37 Issue 8, p751-758, 8p |
| مصطلحات موضوعية: |
MICRORNA, RNA-binding proteins, GENETIC disorders, COLON cancer, HUMAN genetic variation, LUCIFERASES |
| مستخلص: |
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 3ŒUTR of TGFBR1, which might provide a functional basis for the association in MSS HNPCC. In luciferase assays, the risk-associated allele for rs868 was associated with half the luciferase expression in the presence of miRNA let-7b-5p compared with protective allele, suggesting more binding of let-7b-5p and less TGFBR1 expression. Thus, rs868 potentially is a CRC risk-causing allele. Our results support the concept that rs868 is associated with lower TGFBR1 expression thereby increasing CRC risk. [ABSTRACT FROM AUTHOR] |
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