Tobacco-Related Disease Research Program Funded Publications

Tobacco use remains the single most preventable cause of disease, disability, and death in the United States and in California. The Tobacco-Related Disease Research Program (TRDRP) is one of three entities that constitute California’s program to control tobacco consumption and alleviate the burden of tobacco-related disease. This effort was initiated by Proposition 99, “The Tobacco Tax and Health Protection Act of 1988” which mandated that the Department of Health Services, the Department of Education and the University of California be allocated a portion of the tobacco tax revenue collected to address issues of tobacco consumption and its consequences in the state. Enabling legislation requested that the University of California, in its role as the research arm of the state, “administer a comprehensive grant program to support research efforts related to the prevention, causes, and treatment of tobacco-related diseases” and that “ all qualified investigators, regardless of institutional affiliation, shall have equal access and opportunity to compete for the funds.”

The TRDRP is administered by the University of California and is a program of the Research Grants Program Office (RGPO), Office of Research and Graduate Studies at the University of California, Office of the President.

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S100A8/A9 innate immune signaling as a distinct mechanism driving progression of smoking-related breast cancers

(2025)

Smoking plays an underappreciated role in breast cancer progression, increasing recurrence and mortality in patients. Here, we show that S100A8/A9 innate immune signaling is a molecular mechanism that identifies smoking-related breast cancers and underlies their enhanced malignancy. In contrast to acute exposure, chronic nicotine increased tumorigenicity and reprogrammed breast cancer cells to express innate immune response genes. This required the α7 nicotinic acetylcholine receptor, which elicited dynamic changes in cell differentiation, proliferation, and expression of secreted cytokines, such as S100A8 and S100A9, as assessed by unbiased scRNA-seq. Indeed, pharmacologic or genetic inhibition of S100A8/A9-RAGE receptor signaling blocked nicotine's tumor-promoting effects. We also discovered Syntaphilin (SNPH) as an S100A8/A9-dependent gene enriched specifically in estrogen receptor-negative (ER^-) cancers from former smokers, linking this response to patient disease. Together, our findings describe a new α7 nAChR-S100A8/A9-Syntaphilin immune signaling module that drives nicotine-induced tumor progression and distinguishes smoking-related patient disease as a distinct subset of aggressive breast cancers.

Cover page of Effects of Cigarette Smoking and 3‐Day Smoking Abstinence on Translocator Protein 18 kDa Availability: A [18F]FEPPA Positron Emission Tomography Study

Effects of Cigarette Smoking and 3‐Day Smoking Abstinence on Translocator Protein 18 kDa Availability: A [18F]FEPPA Positron Emission Tomography Study

(2025)

With the many negative health consequences of cigarette smoking, quitting is known to improve health in multiple domains. Using positron emission tomography/computed tomography (PET/CT) scanning, our group previously demonstrated that smokers have lower levels than nonsmokers of translocator protein binding both acutely and following overnight abstinence. Here, we sought to determine the effects of longer smoking abstinence on this marker of gliosis for microglia and astroglia, as well as explore associations between the marker and smoking-related symptoms. This observational study was performed in an academic VA medical centre. Fifty-nine generally healthy Veterans who were either nonsmokers (n = 15) or smokers (n = 44) participated in the study. Participants completed an intake visit to evaluate for inclusion/exclusion criteria, [¹⁸F]FEPPA PET/CT scanning and a structural magnetic resonance imaging scan. Smokers were alternately assigned either to smoke to satiety (n = 24) before scanning or undergo three nights of continuous abstinence prior to scanning using contingency management (n = 20 completed this protocol and scanning). The smoker satiety group had a significantly lower mean whole brain (WB) standardized uptake value (SUV) for [¹⁸F]FEPPA binding than both the nonsmoking (-15.3%) and abstinent smoker (-12.3%) groups. The nonsmoking control and abstinent smoker groups had mean WB SUVs that were not significantly different from one another (3.0% group difference). In an exploratory analysis, a significant inverse relationship was found between WB SUVs and mood ratings for smokers, indicating that higher levels of TSPO binding were associated with worse mood. The central findings here support previous studies demonstrating lower levels of the marker for gliosis in satiated smokers and imply normalization with elimination of cigarette smoke constituents from the body, although other explanations for study results (e.g., alterations in radioligand delivery or clearance of radioligand by cigarette smoke constituents) are possible. These findings may represent a previously unknown health benefit of quitting smoking.

An SSTR2–somatostatin chemotactic axis drives T cell progenitor homing to the intestines

(2025)

Progenitors of intraepithelial T cells (IELps) migrate from the thymus to the intestines after birth where they develop into unconventional TCRγδ and TCRαβ lymphocytes in a process of extrathymic lymphopoiesis within cryptopatches. Mechanisms of IELp migration have remained unclear. Here we show that thymic IELps express the somatostatin receptor SSTR2, which contributes to their homing to the gut. IELp homing is Sstr2 dependent and correlates with neonatal induction of Sst encoding somatostatin in neuroendocrine and lamina propria stromal cells. The SSTR2 ligands somatostatin and cortistatin attract IELps in chemotaxis assays and somatostatin triggers IELp binding to the mucosal vascular addressin MAdCAM1. T cell transduction with Sstr2 confers homing to the neonatal colon. Human fetal thymic IELp-like cells express SSTR2 and intestinal stromal cells express SST at the time of initial T cell population, suggesting conserved mechanisms of progenitor seeding of the developing intestines. These results reveal an unexpected role for the SSTR2-somatostatin axis in early immune system development and describe a new role for a small peptide hormone G-protein-coupled receptor in developmental lymphocyte trafficking.

Daily or Nondaily Vaping and Smoking Cessation Among Smokers

(2025)

Importance

An important public health goal is to increase tobacco cessation, but there is limited research on associations of vaping with tobacco cessation.

Objective

To estimate the association of vaping with long-term tobacco cessation among US cigarette smokers who used electronic nicotine delivery systems (ENDS; ie, e-cigarettes) in 2017.

Design, setting, and participants

This cohort study used a nationally representative sample of US cigarette smokers from the Population Assessment of Tobacco and Health cohort at wave 4 (2017) with follow-up at wave 6 (2021). Data were analyzed from June 2023 to June 2024.

Exposure

Wave 4 ENDS use: daily, nondaily, or no use.

Main outcomes and measures

The primary outcomes were 12 or more months' abstinence from cigarette smoking and 12 or more months' abstinence from both cigarette and ENDS use, ascertained at wave 6. Propensity score matching was used to control confounding on 14 potential confounders, including interest in quitting, income, age, education, nondaily smoking, and presence of a smoke-free home.

Results

A total of 6013 smokers were included in the sample (3634 aged ≥35 years [weighted percentage, 65.2%]; 3182 female [weighted percentage, 46.5%]). Among smokers who vaped daily (228 individuals), an estimated 20.9% (95% CI, 15.0% to 26.8%) were abstinent from cigarette smoking at follow-up, compared with 14.3% abstinence (95% CI, 13.0% to 15.5%) among smokers who did not vape (5070 individuals) and 12.6% abstinence (95% CI, 9.8% to 15.4%) among smokers who vaped nondaily (715 individuals). Compared with similar propensity score-matched smokers who did not vape, smoking cessation was 4.1 percentage points lower among those who vaped daily (95% CI, -11.9 to 3.6 percentage points; P = .30), a nonsignificant difference. Smoking cessation was 5.3 percentage points lower among those who vaped nondaily (95% CI, -9.1 to -1.5 percentage points; P = .01) compared with similar propensity score-matched controls. Considering abstinence from both smoking and vaping, compared with matched controls, smokers who vaped daily had lower abstinence at follow-up by 14.7 percentage points (95% CI, -20.2 to -9.2 percentage points; P < .001), and those who vaped nondaily had lower abstinence by 7.2 percentage points (95% CI, -10.7 to -3.8 percentage points; P < .001).

Conclusions and relevance

In this representative cohort study of US smokers who used ENDS, neither daily nor nondaily vaping was associated with increased smoking cessation, and each was associated with reduced tobacco abstinence, suggesting that careful adjustment of confounding is critical in studies of ENDS and smoking cessation.

Cigarette smoking is associated with reduced neuroinflammation and better cognitive control in people living with HIV

(2025)

People living with HIV (HIV+) are roughly twice as likely to smoke cigarettes (Smok+) as the general population. With the advent of effective antiretroviral therapies, it is increasingly important to understand the effects of chronic HIV infection and cigarette smoking on brain function and cognition since HIV+ individuals have heightened neuroinflammation and cognitive deficits even with such therapies. Based on prior studies demonstrating that smoking reduces a marker for neuroinflammation in HIV- individuals, we hypothesized that HIV+/Smok+ individuals would have less neuroinflammation and better cognitive control than HIV+/Smok- individuals. Fifty-nine participants (HIV-/Smok- [n = 16], HIV-/Smok+ [n=14], HIV+/Smok- [n = 18], and HIV+/Smok+ [n = 11]) underwent baseline eligibility tests, positron emission tomography (PET) scanning to determine levels of a marker for neuroinflammation, and assessment of cognitive control with the reverse-translated 5-choice continuous performance test (5C-CPT), with smokers having smoked to satiety prior to testing. For the PET data, a significant effect of smoking status on whole brain (WB) standardized uptake value (SUV) was found between HIV+/Smok+ and HIV+/Smok- participants (due to 18.8% lower WB SUV in the HIV+/Smok+ group). HIV+/Smok- participants exhibited a mean 13.5% higher WB SUV than HIV-/Smok- participants. For the 5C-CPT, HIV+/Smok+ participants performed significantly better than HIV+/Smok- participants (d prime), and HIV+/Smok- participants performed worse than HIV-/Smok- participants. Thus, HIV+/Smok+ individuals demonstrated lower levels of the neuroinflammation marker and better cognitive control than HIV+/Smok- individuals. Given that HIV+ individuals whose HIV is well-controlled can still have chronic neurocognitive complications, study results suggest possible paths for future research into nicotine-related treatments to prevent such complications.

Clarification Regarding Insurance Disparities Among Patients With Head and Neck Cancer—Reply

(2025)

Association of race and ethnicity with quality of care among head and neck cancer patients in California

(2025)

Background

There are significant racial disparities in head and neck cancer (HNC) outcomes. Racial differences in survival may be explained by differential access to high-quality care. The goal of this study was to evaluate the association of race and ethnicity with the quality of the treating hospital, and receipt of guideline-compliant care among HNC patients.

Methods

Retrospective cohort study of data from the California Cancer Registry dataset linked with discharge records and hospital characteristics. The study cohort included adult patients with HNC diagnosed between January 1, 2010, and December 31, 2019. Outcome measures included the quality of treating hospital, and NCCN guideline-compliant care.

Results

Black (OR 0.76, 95 % CI 0.67 to 0.85) and Hispanic (OR 0.68, 95 % CI 0.63 to 0.74) patients were less likely to be treated in top-quality hospitals compared with non-Hispanic White patients, after adjusting for demographic, and clinical factors. This association disappeared for Black patients, but persisted for Hispanic patients, after additionally adjusting for socioeconomic status and insurance status. Black patients with advanced-stage disease were less likely to be treated with dual-modality therapy (OR 0.82, 95 % CI 0.70 to 0.96), however, this association disappeared after adjusting for demographic, and clinical factors, and hospital quality.

Conclusion

There are significant racial and ethnic disparities in quality of care for patients with HNC. Our findings suggest that differential access to high-quality care may account for some of the racial disparities in HNC survival, and highlight the need for continued investigation into the drivers of racial disparities in HNC outcomes.

M19 Adult Consequences of Repeated Nicotine and Δ9-Tetrahydrocannabinol (THC) Vapor Inhalation in Adolescent Rats

(2025)

Cover page of Effect of a minimum floor price law for tobacco products on tobacco sales in Oakland, California, USA: a synthetic difference-in-differences analysis

Effect of a minimum floor price law for tobacco products on tobacco sales in Oakland, California, USA: a synthetic difference-in-differences analysis

(2025)

Background

In May 2020, Oakland became the most populous city in California to implement a minimum floor price law (MFPL), requiring tobacco retailers to sell cigarettes and cigars at $8 or more per pack/package. Policy enforcement began in August 2020.

Methods

We estimated changes in cigarette and cigar prices and unit sales for Oakland versus a matched comparator during the first 20 months following MFPL implementation using a synthetic difference-in-differences approach. We estimated outcome changes overall and by lower-priced (<$8) versus higher-priced (≥$8) segments based on pre-MFPL prices. We also assessed retailer compliance with the MFPL. We further estimated cross-border shopping as a means of price increase avoidance and substitution to electronic nicotine delivery systems (ENDS) and nicotine replacement therapy (NRT) products as alternative consumer responses to the MFPL.

Results

Retailer compliance was high for cigarettes (97.5%) but extremely low for cigars (7.4%). Lower-priced cigarettes in Oakland exhibited: increased median price per pack of 9.0%, a decline in mean monthly sales of 25.2%, and no evidence of significant cross-border shopping (-1.2%) following MFPL enforcement. Lower-priced cigars in Oakland experienced no price change, yet a large sales decline post-enforcement (-58.8%), with a partially-offsetting increase in cross-border shopping (11.0%) post-enforcement. We observed no significant product substitution to higher-priced cigarettes or cigars nor to ENDS or NRT products.

Conclusions

Oakland's MFPL produced an aggregate decline in cigarette sales of 15%. MFPLs hold promise as a complement to tobacco taxation for reducing tobacco use, especially in localities that pre-empt local tobacco taxation.

Targeting Pancreatic Cancer Cell Stemness by Blocking Fibronectin-Binding Integrins on Cancer-Associated Fibroblasts

(2025)

Significance

Simultaneous targeting of two integrins that function as receptors for FN, a protumor ECM protein, can prevent fibroblasts from supporting the malignant behavior of pancreatic cancer cells.