Genetic variation in vitamin D-related genes and risk of colorectal cancer in African Americans

PurposeDisparities in both colorectal cancer (CRC) incidence and survival impact African Americans (AAs) more than other US ethnic groups. Because vitamin D is thought to protect against CRC and AAs have lower serum vitamin D levels, genetic variants that modulate the levels of active hormone in the tissues could explain some of the cancer health disparity. Consequently, we hypothesized that genetic variants in vitamin D-related genes are associated with CRC risk.MethodsTo test this hypothesis, we studied 39 potentially functional single-nucleotide polymorphisms (SNPs) in eight genes (CYP2R1, CYP3A4, CYP24A1, CYP27A1, CYP27B1, GC, DHCR7, and VDR) in 961 AA CRC cases and 838 healthy AA controls from Chicago and North Carolina. We tested whether SNPs are associated with CRC incidence using logistic regression models to calculate p values, odds ratios, and 95% confidence intervals. In the logistic regression, we used a log-additive genetic model and used age, gender, and percent West African ancestry, which we estimated with the program STRUCTURE, as covariates in the models.ResultsA nominally significant association was detected between CRC and the SNP rs12794714 in the vitamin D 25-hydroxylase gene CYP2R1 (p=0.019), a SNP that has previously been associated with serum vitamin D levels. Two SNPs, rs16847024 in the GC gene and rs6022990 in the CYP24A1 gene, were nominally associated with left-sided CRC (p=0.015 and p=0.018, respectively).ConclusionsOur results strongly suggest that genetic variation in vitamin D-related genes could affect CRC susceptibility in AAs. Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-014-0361-y) contains supplementary material, which is available to authorized users

Infra-Inguinal Aneurysms – Threat to Life and Limb?

Objectives: To assess the outcomes of infra-inguinal aneurysms admitted to a regional vascular unit.Methods: All patients admitted with a primary diagnosis of infra inguinal aneurysms were identified from clinical coding lists over a four-year period (January 2008–May 2012). All patients were identified through clinical coding and records were checked to confirm diagnosis, management and outcome, with data analysed using SPSS v18.Results: 39 patients (mean age 58.3yr, range 18-98), of which 27 were male, were identified (24 PseudoAneurysms (PA), 12 True Aneurysms (TA) and 3 Mycotic Aneurysms (MA)). The majority of the PAs were secondary to Intravenous Drug Abuse, IVDA (41%), followed by interventional procedures (29%), vascular anastomotic sites (13%), orthopaedic surgery (13%) and penetrating trauma (4%). 11/12 (92%) TAs were popliteal in origin, with 22/24 (92%) of PAs located at or around the femoral bifurcation. 22/24 of PA (12 surgical; 4 endovascular stenting; 1 ultrasound guided thrombin injection; 4 ultrasound guided compression; 1 embolisation), 8/12 of TA (7 surgical; 1 endovascular stenting) and 3/3 MA (2 surgical; 1 combined surgical + endovascular stenting) required intervention. One patient underwent primary major amputation (popliteal TA) with a further three patients requiring major amputation post intervention (1 MA post bypass procedure, 1 PA post vessel ligation, 1 PA secondary to percutaneous intervention presenting with distal embolization requiring vessel ligation). Overall 30-day mortality was 5.1% (n=2).Conclusions: Our results suggest that the risk of major amputation and mortality secondary to infra-inguinal aneurysms as a pathology is significant.</p