Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy.

Single nucleotide polymorphisms (SNPs) in the promoter region of FAS and FASLG may alter their transcriptional activity. Thus, we determined the associations between four FAS and FASLG promoter variants (FAS1377G>A, rs2234767; 670A>G, rs1800682; FASLG844T>C, rs763110 and 124A>G, rs5030772) and the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated the associations between FAS and FASLG genetic variants and the risk of recurrence in a cohort of 1,008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. Compared with patients with common homozygous genotypes of FAS670 and FASLG844 polymorphisms, patients with variant genotypes had lower disease-free survival rates (log-rank p < 0.0001 and p < 0.0001, respectively) and an approximately threefold higher risk of SCCOP recurrence (HR, 3.2;95% CI, 2.2-4.6; and HR, 3.1; 95% CI, 2.2-4.4, respectively) after multivariate adjustment. Furthermore, among patients with HPV16-positive tumors, those with variant genotypes of these two polymorphisms had lower disease-free survival rates (log-rank, p < 0.0001 and p < 0.0001, respectively) and a higher recurrence risk than did patients with common homozygous genotypes (HR, 12.9; 95% CI, 3.8-43.6; and HR, 8.1; 95% CI, 3.6-18.6, respectively), whereas no significant associations were found for FAS1377 and FASLG124 polymorphisms. Our findings suggest that FAS670 and FASLG844 polymorphisms modulate the risk of recurrence of SCCOP, particularly in patients with HPV16-positive tumors. Larger studies are needed to validate these results.

Component-wise gradient boosting and false discovery control in survival analysis with high-dimensional covariates.

MOTIVATION: Technological advances that allow routine identification of high-dimensional risk factors have led to high demand for statistical techniques that enable full utilization of these rich sources of information for genetics studies. Variable selection for censored outcome data as well as control of false discoveries (i.e. inclusion of irrelevant variables) in the presence of high-dimensional predictors present serious challenges. This article develops a computationally feasible method based on boosting and stability selection. Specifically, we modified the component-wise gradient boosting to improve the computational feasibility and introduced random permutation in stability selection for controlling false discoveries. RESULTS: We have proposed a high-dimensional variable selection method by incorporating stability selection to control false discovery. Comparisons between the proposed method and the commonly used univariate and Lasso approaches for variable selection reveal that the proposed method yields fewer false discoveries. The proposed method is applied to study the associations of 2339 common single-nucleotide polymorphisms (SNPs) with overall survival among cutaneous melanoma (CM) patients. The results have confirmed that BRCA2 pathway SNPs are likely to be associated with overall survival, as reported by previous literature. Moreover, we have identified several new Fanconi anemia (FA) pathway SNPs that are likely to modulate survival of CM patients. AVAILABILITY AND IMPLEMENTATION: The related source code and documents are freely available at https://sites.google.com/site/bestumich/issues. CONTACT: yili@umich.edu.

"Thinking too much": A systematic review of a common idiom of distress.

Idioms of distress communicate suffering via reference to shared ethnopsychologies, and better understanding of idioms of distress can contribute to effective clinical and public health communication. This systematic review is a qualitative synthesis of "thinking too much" idioms globally, to determine their applicability and variability across cultures. We searched eight databases and retained publications if they included empirical quantitative, qualitative, or mixed-methods research regarding a "thinking too much" idiom and were in English. In total, 138 publications from 1979 to 2014 met inclusion criteria. We examined the descriptive epidemiology, phenomenology, etiology, and course of "thinking too much" idioms and compared them to psychiatric constructs. "Thinking too much" idioms typically reference ruminative, intrusive, and anxious thoughts and result in a range of perceived complications, physical and mental illnesses, or even death. These idioms appear to have variable overlap with common psychiatric constructs, including depression, anxiety, and PTSD. However, "thinking too much" idioms reflect aspects of experience, distress, and social positioning not captured by psychiatric diagnoses and often show wide within-cultural variation, in addition to between-cultural differences. Taken together, these findings suggest that "thinking too much" should not be interpreted as a gloss for psychiatric disorder nor assumed to be a unitary symptom or syndrome within a culture. We suggest five key ways in which engagement with "thinking too much" idioms can improve global mental health research and interventions: it (1) incorporates a key idiom of distress into measurement and screening to improve validity of efforts at identifying those in need of services and tracking treatment outcomes; (2) facilitates exploration of ethnopsychology in order to bolster cultural appropriateness of interventions; (3) strengthens public health communication to encourage engagement in treatment; (4) reduces stigma by enhancing understanding, promoting treatment-seeking, and avoiding unintentionally contributing to stigmatization; and (5) identifies a key locally salient treatment target.