Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant.

PURPOSE: Leukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM). METHODS: Whole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes. RESULTS: In P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response." CONCLUSIONS: We identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.

Financial Incentives for Smoking Cessation Among Socioeconomically Disadvantaged Adults: A Randomized Clinical Trial.

Importance: Socioeconomically disadvantaged individuals (ie, those with low socioeconomic status [SES]) have difficulty quitting smoking and may benefit from incentive-based cessation interventions. Objectives: To evaluate the impact of incentivizing smoking abstinence on smoking cessation among adults with low SES. Design, Setting, and Participants: This study used a 2-group randomized clinical trial design. Data collection occurred between January 30, 2017, and February 7, 2022. Participants included adults with low SES who were willing to undergo smoking cessation treatment. Data were analyzed from April 18, 2023, to April 19, 2024. Interventions: Participants were randomized to usual care (UC) for smoking cessation (counseling plus pharmacotherapy) or UC plus abstinence-contingent financial incentives (UC plus FI). Main Outcomes and Measures: The primary outcome was biochemically verified 7-day point prevalence smoking abstinence (PPA) at 26 weeks after the quit date. Secondary outcomes included biochemically verified 7-day PPA at earlier follow-ups, 30-day PPA at 12 and 26 weeks, repeated 7-day PPA, and continuous abstinence. Multiple approaches were employed to handle missing outcomes at follow-up, including categorizing missing data as smoking (primary), complete case analysis, and multiple imputation. Results: The 320 participants had a mean (SD) age of 48.9 (11.6) and were predominantly female (202 [63.1%]); 82 (25.6%) were Black, 15 (4.7%) were Hispanic, and 200 (62.5%) were White; and 146 (45.6%) participated during the COVID-19 pandemic. Overall, 161 were randomized to UC and 159 were randomized to UC plus FI. After covariate adjustment with missing data treated as smoking, assignment to UC plus FI was associated with a greater likelihood of 7-day PPA at the 4-week (adjusted odds ratio [AOR], 3.11 [95% CI, 1.81-5.34]), 8-week (AOR, 2.93 [95% CI, 1.62-5.31]), and 12-week (AOR, 3.18 [95% CI, 1.70-5.95]) follow-ups, but not at the 26-week follow-up (22 [13.8%] vs 14 [8.7%] abstinent; AOR, 1.79 [95% CI, 0.85-3.80]). However, the association of group assignment with smoking cessation reached statistical significance at all follow-ups, including 26 weeks, with multiple imputation (37.37 [23.5%] in the UC plus FI group vs 19.48 [12.1%] in the UC group were abstinent; AOR, 2.29 [95% CI, 1.14-4.63]). Repeated-measures analyses indicated that participants in the UC plus FI group were significantly more likely to achieve PPA across assessments through 26 weeks with all missing data estimation methods. Other secondary cessation outcomes also showed comparable patterns across estimation methods. Participants earned a mean (SD) of $72 ($90) (of $250 possible) in abstinence-contingent incentives. Participation during the COVID-19 pandemic reduced the likelihood of cessation across assessments. Conclusions and Relevance: In this randomized clinical trial, incentivizing smoking cessation did not increase cessation at 26 weeks when missing data were treated as smoking; however, the UC plus FI group had greater odds of quitting at follow-ups through 12 weeks. Cessation rates were higher for the UC plus FI group at all follow-ups through 26 weeks when multiple imputation was used to estimate missing outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02737566.