| Autor: |
W, Wang, S, Xue, S A, Ingles, Q, Chen, A T, Diep, H D, Frankl, A, Stolz, R W, Haile |
| Rok vydání: |
2001 |
| Předmět: |
|
| Zdroj: |
Cancer epidemiology, biomarkersprevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 10(9) |
| ISSN: |
1055-9965 |
| Popis: |
Epidemiological and experimental studies have implicated bile acids (particularly secondary bile acids) as important factors in the development of colorectal cancer. The ileal sodium-dependent bile acid transporter (ISBT) is a crucial player in the enterohepatic circulation of bile acids. Genetic defects in ISBT may result in malabsorption of bile acids and a loss of bile acids into the large intestine, with a resultant increase in the cytotoxic secondary bile acids in the colon. In a case-control study, we investigated the association between two sequence variations in SLC10A2, the gene encoding ISBT, and colorectal adenomas, a precursor lesion of colorectal cancer. The frequency of the missense mutation in codon 171 of exon 3 (a nucleotide transversion from G to T resulting in an alanine to serine substitution) was not significantly different between cases and controls. However, we found a 2-fold higher risk of colorectal adenomas associated with a C--T nucleotide transition in codon 169 of exon 3 (odds ratio = 2.06; 95% confidence interval: 1.10-3.83). Logistic regression analysis using A171S/169 C--T haplotypes as the allelic markers showed that among AA wild-type homozygotes for A171S mutation, this C--T nucleotide transition in codon 169 was associated with a 2.42 times increased risk (odds ratio = 2.42; 95% confidence interval: 1.26-4.63). This initial observation of an association between a polymorphism in the SLC10A2 gene and the risk of colorectal adenomatous polyps would, if confirmed by other studies, support the role of bile acids in the carcinogenesis of colorectal cancer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
