Association of the OCTN1/1672T variant with increased risk for colorectal cancer in young individuals and ulcerative colitis patients

作者：Martini Maurizio; Ferrara Anna Maria; Giachelia Manuela; Panieri Emiliano; Siminovitch Katherine; Galeotti Tommaso; Larocca Luigi Maria; Pani Giovambattista^*

来源：Inflammatory Bowel Diseases, 2012, 18(3): 439-448.

DOI：10.1002/ibd.21814

• cancer in IBD
• basic science
• clinical
• OCTN1
• OCTN2

Background: Ulcerative colitis (UC) is associated with colorectal cancer. Chronic inflammation may also play a role in the pathogenesis of sporadic colorectal cancer (SCC), particularly in younger patients (%26lt;55 years). We evaluated whether single nucleotide polymorphisms of the OCTN1 and OCTN2 genes are associated with UC, SCC, and with UC cases with cancer progression (UCCP). %26lt;br%26gt;Methods: We evaluated the OCTN1 and OCTN2 polymorphisms in 200 patients with UC, 59 patients with UCCP, 200 patients with SCC, and 200 controls (HC). IL-8 expression was also assessed by real-time polymerase chain reaction (PCR). Additionally, we trtmsfected human colon carcinoma Caco2 cells, homozygous for OCTN1/1672T variant, with the OCTN1/1672C allele and NF-kappa B activity was evaluated by luciferase based reporter assay and IL-8 mRNA expression by real-time PCR. %26lt;br%26gt;Results: OCTN2 polymoiphisms did not present a significant association with any group of patients compared to normal controls. Conversely, homozygosity for the OCTN1/1672T variant was significantly associated with UC (P = 0.047 vs. HC), with UCCP (UCCP vs. HC, P %26lt; 0.001), and with SCC developing in early age (%26lt;55 years) (P = 0.021 vs. HC). Importantly, IL-8 mRNA expression was higher in UC and UCCP patients homozygous for the OCTN1 1672T variant compared to the other genotypes. Moreover, in Caco2 cells transfection of the OCTN1/1672C variant reduced the activity of the proinflammatory factor NF-kappa B. %26lt;br%26gt;Conclusion: Our data demonstrate that OCTN1 could have a role in modulating the severity of chronic inflammation associated with SCC in early age and in VC patients, and that its polymorphisms may help to predict malignant progression of IBD.

• 出版日期2012-3