Pervasive Induction of Regulatory Mutation Microclones in Sun-exposed Skin.

Carcinogen-induced mutations are thought near-random, with rare cancer-driver mutations underlying clonal expansion. Using high-fidelity Duplex Sequencing to reach a mutation frequency sensitivity of 4×10 -9 per nt, we report that sun exposure creates pervasive mutations at sites with ∼100-fold UV-sensitivity in RNA-processing gene promoters - cyclobutane pyrimidine dimer (CPD) hyperhotspots - and these mutations have a mini-driver clonal expansion phenotype. Numerically, human skin harbored 10-fold more genuine mutations than previously reported, with neonatal skin containing 90,000 per cell; UV signature mutations increased 8,000-fold in sun-exposed skin, averaging 3×10 -5 per nt. Clonal expansion by neutral drift or passenger formation was nil. Tumor suppressor gene hotspots reached variant allele frequency 0.1-10% via 30-3,000 fold clonal expansion, in occasional biopsies. CPD hyperhotspots reached those frequencies in every biopsy, with modest clonal expansion. In vitro, tumor hotspot mutations arose occasionally over weeks of chronic low-dose exposure, whereas CPD hyperhotspot mutations arose in days at 1000-fold higher frequencies, growing exponentially. UV targeted mini-drivers in every skin cell.

Effect of a Personalized Tobacco Treatment Intervention on Smoking Abstinence in Individuals Eligible for Lung Cancer Screening.

INTRODUCTION: To determine whether personalized gain-framed messaging and biomarker feedback related to tobacco cessation or reduction decrease smoking behavior in patients undergoing or eligible for lung cancer screening. METHODS: Between 2016 and 2020, 188 patients were enrolled in a two-phase, sequential, randomized controlled trial. Phase 1 evaluated whether standard of care (SC) (five in-person counseling sessions and 8 weeks of nicotine patch) plus gain-framed messaging (GFM) versus SC would increase 8-week biochemically verified smoking cessation rates. In 143 participants randomized in phase 2, we tested whether feedback on smoking-related biomarkers would reduce 6-month self-reported number of cigarettes smoked per day compared with a no feedback control. Chi-square test and mixed effects repeated measures analyses were used to evaluate group differences. RESULTS: Participants were 62.5 ± 5.6 (mean ± SD) years of age, had a 50.3 ± 21 pack-year smoking history, and were smoking 16.9 ± 9.9 cigarettes per day. At 8 weeks, there was no difference in quit rates between those randomized to SC plus GFM (n = 15 of 93, 16.1%) and those randomized to SC (n = 16 of 95, 16.8%), with p equals to 0.90. At the 6-month post-randomization follow-up, number of cigarettes smoked per day was similar in the feedback (least-squares mean = 7.5, 95% confidence interval: 6.0-9.1) and no feedback arms (7.7, 95% confidence interval: 6.2-9.3), with p equals to 0.87. CONCLUSIONS: Gain-framed messaging and health feedback did not significantly improve quit rates relative to comprehensive standard of care. Nevertheless, the overall program achieved clinically meaningful smoking quit rates in this older high pack-year cohort, highlighting the importance of intensive tobacco treatment for patients undergoing lung cancer screening. CLINICAL TRIAL REGISTERED WITH CLINICALTRIALS.GOV: NCT02658032.

Examining Tobacco Treatment Perceptions and Barriers among Black versus Non-Black Adults Attending Lung Cancer Screening.

The US Preventive Services Task Force recommends annual lung cancer screening for patients at high risk based on age and smoking history. Understanding the characteristics of patients attending lung cancer screening, including potential barriers to quitting smoking, may inform ways to engage these high-risk patients in tobacco treatment and address health disparities. Patients attending lung cancer screening who currently smoke cigarettes completed a survey at Smilow Cancer Hospital at Yale-New Haven (N = 74) and the Medical University of South Carolina (N = 73) at the time of their appointment. The survey assessed demographics, smoking history, and perceptions and concerns about quitting smoking.Patients were 55 to 76 years old (mean = 63.3, SD = 5.3), N = 64 (43.5%) female, and N = 31 (21.1%) non-Hispanic Black. Patients smoked 16.3 cigarettes per day on average (SD = 9.2) and rated interest in quitting smoking in the next month as moderate (mean = 5.6, SD = 3.1, measured from 0 = "very definitely no" to 10 = "very definitely yes"). The most frequently endorsed concerns about quitting smoking were missing smoking (70.7%), worry about having strong urges to smoke (63.9%), and concerns about withdrawal symptoms (59.9%). In comparison with other races/ethnicities, Black patients were less likely to report concerns about withdrawal symptoms and more likely to report smoking less now and perceiving no need to quit. Findings identified specific barriers for tobacco treatment and differences by race/ethnicity among patients attending lung cancer screening, including concerns about withdrawal symptoms and perceived need to quit. Identifying ways to promote tobacco treatment is important for reducing morbidity and mortality among this high-risk population. PREVENTION RELEVANCE: The current study examines patient characteristics and tobacco treatment perceptions and barriers among patients attending lung cancer screening who continue to smoke cigarettes that may help inform ways to increase treatment engagement and address tobacco-related health disparities to reduce morbidity and mortality from smoking.

How to word effective messages about smoking and oral health: emphasize the benefits of quitting.

This project examined whether smokers differentially responded to messages about oral health that emphasized either the benefits of quitting smoking or the risks of continued smoking. Messages concerning oral health and smoking were developed to emphasize the benefits of quitting smoking (gain-framed) or the costs of continued smoking (loss-framed). These messages were embedded in recruitment brochures for smoking cessation trials, which were placed in twenty dental office waiting rooms for a six-month period. The number of brochures taken from the waiting rooms was tracked, as well as calls to inquire about smoking cessation studies. As hypothesized, dental patients were more likely to acquire gain-framed brochures. Out of 271 brochures taken from the dental office waiting rooms, significantly more brochures contained gain-framed messages compared to loss-framed messages (59 percent vs. 41 percent, p<.05). There was an equal number of calls to inquire about smoking cessation studies for each message type. Overall, individuals in dental office waiting rooms were more likely to take brochures about smoking cessation trials that contained gain-framed messages concerning oral health and smoking. Information about oral health and smoking typically emphasizes the dangers of continued smoking. This study found that smokers are more receptive to information that emphasizes the benefits of quitting.