No abstract

Injecting drug users and prisoners have high prevalences of antibodies to hepatitis A-C. The aim of this study was to determine the prevalence of antibodies to hepatitis E virus (anti-HEV) in two Danish high-risk populations and correlate anti-HEV with risk factors for transmission. Three hundred thirty male prisoners and 137 patients at a drug treatment center were tested for anti-HEV with an in-house enzyme-linked immunoassay (EIA) utilizing antigens derived from open reading frame 2 (ORF2). This was compared with a commercial test with antigens derived from ORF2 and ORF3 (Abbott HEV EIA). In addition the samples were tested for antibodies against hepatitis A-C viruses, human immunodeficiency virus (HIV) 1 and 2, human T lymphotropic virus (HTLV) I and II and herpes simplex virus type 2 (HSV2). The participants were interviewed about risk factors for transmission. The anti-HEV prevalence was 16.9% (95% CI 14-21) for the in-house assay compared to 4.1% (95% CI 2.5-6.3) with the commercial assay. The correlation between the two assays was low (87% overall agreement; kappa value 0.32). One sample was strongly anti-HEV IgM positive, suggesting recent HEV infection inside Denmark. The presence of anti-HEV was associated significantly with anti-HAV among prisoners and increased with age in both groups. In contrast, associations were not found with injecting drug use or sexual risk factors. With the commercial assay an increased prevalence of anti-HEV was found among participants who had spent more than 5 years outside Northern Europe. In conclusion, anti-HEV was highly prevalent among Danish prisoners and drug users but not related to risk factors for blood-borne or sexual transmission.

Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72–0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy‐free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63–2.24; ptrend = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.

Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case-control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1 rs2237892T allele or the CDKN2A-2B rs2383208G/G , IGF1 rs35767T/T and MADD rs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)Z1.32-2.13) whereas those carrying the KCNJ11 rs5215C , KCNJ11 rs5219T and THADA rs7578597C alleles or the FTO rs8050136A/A and LTA rs1041981C/C genotypes showed a significantly decreased risk of developing the disease (ORZ0.76-0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)Z0.645 vs AUCZ0.629; PZ4.05! 10 K06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30 rs2641348 and NOTCH2 rs10923931 variants (P interaction Z0.001 and 0.0004, respectively). Men carrying the ADAM30 rs2641348C and NOTCH2 rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (OR M Z0.71 and OR M Z0.66 vs OR W Z1.22 and OR W Z1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.