A variant (rs932335) in the HSD11B1 gene is associated with colorectal cancer in a Chinese population.

Glucocorticoid hormones have been reported to contribute to the regulation of cellular proliferation and differentiation and to inhibit the growth of cells in several colon tumors and adenocarcinoma cell lines. As a regulator of glucocorticoid levels, type I isoform HSD11B1 is a bidirectional enzyme but acts predominantly as an oxidoreductase to yield active glucocorticoids, cortisol or corticosterone. To date, studies investigating the associations between the polymorphisms of HSD11B1 and the risk for cancer have shown inconclusive results. In our study, we aimed to investigate whether the polymorphisms of HSD11B1 may influence the genetic susceptibility to colorectal cancer (CRC) in a Chinese population. Four single-nucleotide polymorphisms of HSD11B1 (rs846910 G/A, rs11807619 G/T, rs932335 C/G, and rs13306421 G/A) were detected using a PCR-ligase detection reaction in a case-control study comprising 110 CRC patients and 118 controls. Logistic regression was used to evaluate genetic associations with the occurrence of CRC. Real-time PCR was used to test the mRNA expression of HSD11B1 in 18 CRC tissues. The frequencies of the rs932335 GC genotype were significantly higher among the patients compared with controls (P=0.019). Compared with individuals carrying the GG genotype, individuals with the GC/CC genotype had a significantly increased susceptibility to CRC occurrence (odds ratio=2.23, 95% confidence interval=1.27-3.94, P=0.008). In cancer tissues, patients carrying the GG genotype also displayed an increased mRNA level of HSD11B1 (P=0.019). These results suggested that the HSD11B1 rs932335 G/C polymorphism had an effect on CRC occurrence. These findings also suggest that the functional polymorphism rs932335 in intron4 of HSD11B1 may influence the susceptibility to and progression of CRC in a Chinese population. Large population-based prospective studies are required to validate our findings.