Measuring blood cell DNA damage using the PIG-A mutation and CBMN assay in pancreatic cancer patients: a pilot study.

Pancreatic cancer still has one of the worst prognoses of all solid malignancies, despite developments in cancer knowledge and care. Research into pancreatic cancer has not fully translated into clinical improvements and as a result, fewer than 1% of patients survive 10 years post-diagnosis. This bleak outlook for patients could be improved by earlier diagnosis. The human erythrocyte phosphatidylinositol glycan class A (PIG-A) assay monitors the mutation status of the X-linked PIG-A gene by measuring glycosyl phosphatidylinositol (GPI)-anchored proteins on the extracellular surface. We have previously identified an elevated PIG-A mutant frequency in oesophageal adenocarcinoma patients and here investigate whether this could be seen in a pancreatic cancer cohort, given the urgent need for novel pancreatic cancer biomarkers. In our pilot study, an elevated PIG-A mutant frequency (5.775 × 10-6 (95% CI 4.777-10) mutants per million) was seen in pancreatic cancer patients (n = 30) when compared to the non-cancer control group (n = 14) who had an erythrocyte mutant frequency of 4.211 × 10-6 (95% CI 1.39-5.16) mutants per million (p = 0.0052). A cut-off value of 4.7 mutants per million provided an AUROC of 0.7595 with a sensitivity of 70% and specificity of 78.57%. A secondary measure of DNA damage in an alternative blood cell population also showed an increase in peripheral lymphocytes using the cytokinesis-block micronucleus assay (p = 0.0164) (AUROC = 0.77, sensitivity = 72.22%, specificity = 72.73%). The micronucleus frequency and PIG-A status show some potential as blood-based biomarkers of pancreatic cancer, but further investigations of these DNA damage tests are required to assess their utility in pancreatic cancer diagnosis.

Key personality traits and alcohol use disorder symptoms in first and second year college students: detangling antecedent from consequence.

BACKGROUND: Studies have consistently shown that low constraint and high negative emotionality are associated with higher levels of alcohol use and greater alcohol related problems. Less research has examined associations between these traits and alcohol use disorder (AUD) from the first to second year of college, when alcohol use increases rapidly, or has evaluated gender differences in these associations. METHODS: The longitudinal College Experiences Study (N = 209, 60% female, 90% white) was used to detangle antecedent vs. consequence between constraint, negative emotionality, and AUD symptoms using multiple methods (cross-lagged panel analysis, latent difference score approach). RESULTS: Providing evidence for a scar/complication model, greater AUD symptoms in the first year of college was predictive of rank-order and correlated decreases in constraint in the second year, but only for males. Surprisingly, negative emotionality was not associated with AUD symptoms for either gender. Qualitative analyses show that the vast majority of those that met an AUD diagnosis (90%+) did not consider their drinking to be problematic. CONCLUSION: Given the vast majority of college students with AUD do not perceive their drinking to be problematic, results support the potential of using personality-based risk prevention/intervention programs to target at-risk individuals for problematic drinking, rather than targeting problematic drinking alone.