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Antidepressant Use and Risk of Colorectal Cancer in The Women\u27s Health Initative
Colorectal cancer is the third most common cancer among U.S. women; 63,610 new cases were estimated to have occurred in 2015. Prior studies found a reduced risk of colorectal cancer among antidepressant (AD) users, however, none adjusted for depression, which is itself linked to increased colorectal cancer risk and could confound this relationship. We assessed the relationship between ADs and AD drug classes with risk of colorectal cancer in a prospective cohort of 145,190 women between the ages of 50-79 without a previous history of cancer at enrollment. Current AD use was assessed at baseline. Over an average follow-up of 14 years, there were 5,280 incident cases of colorectal cancer cases. Cox proportional hazard ratios, adjusted for potential confounders including depressive symptoms, were used to estimate hazard ratios. Of all AD users, 51.1% used selective serotonin reuptake inhibitors (SSRIs), 40.7% used tricyclic antidepressants (TCAs), and 15.1% used other ADs. No association was observed between total AD use, SSRI use, and/or other ADs and risk of colorectal cancer. We observed a reduced risk of colorectal cancer among TCA users, which was significant for colon cancer specifically (HR 0.68, 95% CI: 0.48-0.96). Although a reduced risk of colon cancer was observed for TCAs use for less than two years (HR 0.39, 95%: CI 0.19-0.82), no association was observed for TCA use for two or more years (HR 0.85, 95%CI: 0.57-1.26). Our data suggests a protective association between TCA use and risk of colorectal cancer, however more research is needed to verify these findings
CSK regulatory polymorphism is associated with systemic lupus erythematosus and influences B-cell signaling and activation
Item does not contain fulltextThe c-Src tyrosine kinase, Csk, physically interacts with the intracellular phosphatase Lyp (encoded by PTPN22) and can modify the activation state of downstream Src kinases, such as Lyn, in lymphocytes. We identified an association of CSK with systemic lupus erythematosus (SLE) and refined its location to the intronic polymorphism rs34933034 (odds ratio (OR) = 1.32; P = 1.04 x 10(-9)). The risk allele at this SNP is associated with increased CSK expression and augments inhibitory phosphorylation of Lyn. In carriers of the risk allele, there is increased B-cell receptor (BCR)-mediated activation of mature B cells, as well as higher concentrations of plasma immunoglobulin M (IgM), relative to individuals with the non-risk haplotype. Moreover, the fraction of transitional B cells is doubled in the cord blood of carriers of the risk allele, due to an expansion of late transitional cells in a stage targeted by selection mechanisms. This suggests that the Lyp-Csk complex increases susceptibility to lupus at multiple maturation and activation points in B cells