Smoking-related Cancers Research Articles

Trigeminal neuralgia and risk of cancer: A population-based cohort study.

Evidence of an association between trigeminal neuralgia (TN) and subsequent cancer risk remains sparse. The present study aimed to examine the association between TN and cancer risk in the Danish population. A nationwide population-based cohort study using hospital diagnoses collected routinely and prospectively from Danish population-based registries in 1994-2022. We identified 7846 individuals with a first-time diagnosis of TN. Within one year of diagnosis, we observed 193 cancer cases (standardized incidence rate (SIR) = 2.45, 95% confidence interval (CI) = 2.11-2.82). Absolute risk (AR) for all cancers within one year of TN diagnosis was 2.5% (95% CI = 2.2-2.9). Cancers of the head, neck and nervous system were most strongly associated with TN (AR 0.9% (95% CI = 0.7-1.1); SIR = 13.5 (95% CI = 10.5-17.0)) and the risk was persistently elevated one year after TN diagnosis. We observed 827 cancer diagnoses beyond one year after TN diagnosis, where smoking related cancers were associated with elevated cancer risk (SIR 1.13 = (95% CI = 0.98-1.29)). TN was associated with an elevated risk of cancers of the head, neck and nervous system including site-specific cancers in the area. Our results suggest the potential importance of smoking related tumors in TN, either as a symptom, cause or shared risk factor.

Abstract B021: Quitxt research study: A mobile messaging intervention to promote smoking cessation among young adult smokers in South Texas

Abstract Background: Despite major advances in tobacco control and treatment, tobacco use remains the single largest preventable cause of morbidity and mortality in the US. Smoking prevalence is highest among Texas young adults (ages 18-29), especially those with lower education and income and those living in rural areas, like Latinos. About 19.2% of Latinos ages 18-29 in the study areas are current smokers, putting them at higher risk of cancer and other tobacco-related morbidity and mortality. Young adults are heavy users of smartphones, text messaging, social media chats, and other mobile social media, providing a remarkable opportunity for innovation in the delivery of health promotion interventions to reduce health disparities in this large and rapidly growing racial/ethnic population. This research study aims to assess the effectiveness of Quitxt, our culturally appropriate mobile smoking cessation program. Quitxt – launched by our interdisciplinary research team using proven social cognitive, motivational interviewing, and brief intervention methods for promoting behavior change – blends bilingual text and social media messaging for smoking cessation tailored to the language and culture of young adult smokers in our vulnerable region of South Texas. The team also adapted the program to the Primary Care and Mays Cancer Center patient population, and it is currently being implemented. Quitxt has not been tested in a research study, as its creation as an evidence-based cancer prevention service for young adult smokers was supported by the Cancer Prevention and Research Institute of Texas. Methods: The proposed 5-year study involves a 2-group parallel randomized controlled trial with 4 assessments (baseline, 1, 3, and 6 months) and will recruit 1,200 young adult Latino smokers: 1)The intervention group will receive Quitxt (text messaging or chat); and 2) the usual care group will receive abbreviated text messaging with health promotion-related content, including smoking cessation and referral to the Texas DSHS cessation program YesQuit. Smoking cessation will be validated via biological tests for those who report smoking cessation at the study follow-ups. We hypothesize that the group receiving the Quitxt intervention will achieve significantly higher smoking cessation rates than the group receiving usual care. Results: The proposed intervention will mark the first significant study to assess the effectiveness of an innovative, bilingual, culturally, and linguistically appropriate mobile cessation intervention tailored to young adult Latinos living in South Texas by enhancing their skills development, competence, and self-efficacy to initiate and maintain cessation. Conclusion: This study will advance public health by testing the effectiveness of a scalable, evidence-based, easily disseminated, and adaptable intervention with potentially broad national reach to help young adults stop smoking and reduce smoking-related cancer and chronic disease morbidity and mortality and their associated healthcare costs. Citation Format: Patricia Chalela, Vivian Cortez, Sandra Sivak, Armida Flores, Martha De La Mora, Zully Garcia, Byeongyeob Choi, Edgar Muñoz, Cliff Despres, Alfred L. McAlister, Qurathul Ahmed, Audrey Cordova, Maria I. Sung-Cuadrado, Luis F. Velez, Sahak Kaghyan, Rahul Mundlamuri, David Akopian, Amelie G. Ramirez. Quitxt research study: A mobile messaging intervention to promote smoking cessation among young adult smokers in South Texas [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B021.

Estimating Additive Interaction in Two-Stage Individual Participant Data Meta-Analysis.

Individual participant data (IPD) meta-analysis provides important opportunities to study interaction and effect modification for which individual studies often lack power. While previous meta-analyses have commonly focused on multiplicative interaction, additive interaction holds greater relevance for public health and may in certain contexts better reflect biological interaction. Methodological literature on interaction in IPD meta-analysis does not cover additive interaction for models including binary or time-to-event outcomes. We aimed to describe how the Relative Excess Risk due to Interaction (RERI) and other measures of additive interaction or effect modification can be validly estimated within two-stage IPD meta-analysis. First, we explain why direct pooling of study-level RERI estimates may lead to invalid results. Next, we propose a three-step procedure to estimate additive interaction: 1) estimate effects of both exposures and their product term on the outcome within each individual study; 2) pool study-specific estimates using multivariate meta-analysis; 3) estimate an overall RERI and 95% confidence interval based on the pooled effect estimates. We illustrate this procedure by investigating interaction between depression and smoking and risk of smoking-related cancers using data from the PSYchosocial factors and Cancer (PSY-CA) consortium. We discuss implications of this procedure, including the application in meta-analysis based on published data.

Epigenomic Dysregulation in Youth Vapers: Implications for Disease Risk Assessment.

Despite the ongoing epidemic of youth vaping, the long-term health consequences of electronic cigarette use are largely unknown. We report the effects of vaping versus smoking on the oral cell methylome of healthy young vapers and smokers relative to non-users. Whereas vapers and smokers differ in number of differentially methylated regions (DMRs) (831 vs 2,863), they share striking similarities in the distribution and patterns of DNA methylation, chromatin states, transcription factor binding motifs, and pathways. There is substantial overlap in DMR-associated genes between vapers and smokers, with the shared subset of genes enriched for transcriptional regulation, signaling, tobacco use disorders, and cancer-related pathways. Of significance is the identification of a common hypermethylated DMR at the promoter of "Hypermethylated In Cancer 1" (HIC1), a tumor suppressor gene frequently silenced in smoking-related cancers. Our data support a potential link between epigenomic dysregulation in youth vapers and disease risk. These novel findings have significant implications for public health and tobacco product regulation.

Risk Factors Associated with Urothelial Bladder Cancer.

Urothelial bladder carcinoma (UBC) is the most frequent histologic form of bladder cancer, constituting 90% of the cases. It is important to know the risk factors of UBC to avoid them and to decrease its recurrence after treatment. The aim of this review was to provide an overview of the risk factors associated with UBC incidence. A comprehensive literature search from 2012 to 2024 was carried out in databases such as PubMed, Google Scholar, and Medline with potential keywords such as "bladder cancer", "urothelial bladder cancer", "incidence of urothelial bladder cancer worldwide", "mortality rate of bladder cancer", "incidence according to gender", "treatment for bladder cancer", and "risk factors of bladder cancer". Smoking tobacco was comprehended to be the major risk factor for UBC. Smoke from tobacco products contains polycyclic aromatic hydrocarbons (PAHs) and aromatic amines such as 4-aminobiphenyl, which are known to cause UBC. Smoking-related bladder cancer mortality ranks just second to smoking-related lung cancer mortality. For non-smokers, pollution became a major risk factor associated with UBC. Polycyclic aromatic hydrocarbons (PAHs) are linked to many cancers, especially to UBC. Indoor and outdoor pollution generates VOCs (volatile organic compounds) and PAHs. Small-particle matter < 2.5 is linked to UBC and lung cancers. Drinking chlorinated water is linked to UBC. Also, swimming in chlorinated pools that produce trihalomethanes increases the risk of many cancers, and especially of bladder cancer. Occupational exposure to carcinogens, specifically aromatic amines, is a significant UBC risk factor. It has been estimated that approximately 20% of all UBCs may be linked to this type of exposure, primarily in industrial settings that treat dye, paint, petroleum chemicals, and metal. The other risk factors included genetics, diet, and medical conditions. Alcohol, consumption of processed meat and whole milk, and higher intakes of selenium and vitamins A and E also contribute to the development of UBC. Further, chemotherapeutic agents, oral hypoglycemic drugs, and radiation therapy are positively associated with UBC. The significance of the initial prevention of UBC must be emphasized, and especially programs for quitting cigarettes should be encouraged and supported. However, smoking is not the only risk factor for UBC. For non-smokers, other risk factors should be investigated. Air and water pollution are linked to UBC. Indoor and outdoor pollution should be more controlled. Patients and people should be informed of the risk of drinking chlorinated water and swimming in chlorinated pools.

The population-based effects of the FDA’s approval of durvalumab as consolidative therapy in patients with locally-advanced non-small cell lung cancer.

e20086 Background: In 2018, consolidative durvalumab (D) was FDA-approved in patients with locally advanced non-small cell lung cancer(NSCLC) because it increased PFS and was later found to increase overall survival (OS). This analysis will check the real-world effects of this agent prior to and after its approval. Methods: The SEER-17 database was queried from 2015-2020 and assessed for differences in OS/lung cancer specific survival (LCSS) and rates of second cancers (2C). Patients included were those with NSCLC who received chemotherapy and radiation with at least 7 months of follow-up. The population was split into two different groups, those diagnosed before and after D’s approval (2015-2017(BA) and 2018-2020(AA). Multi-variate analyses (MVA) were used to find prognostic factors which were used to adjust OS/LCSS rates for the BA and AA at 12, 24, and 30 months. Variables analyzed included patient characteristics, histopathology, and previous cancers (separated into alcohol, diet, smoking, virus and hormone related). Inverse propensity scores were weighted for OS factors to determine rates of second cancers. Results: Of 12,022 patients, 501 patients developed 2Cs. The OS was significantly better for AA group than the BA group ( p &lt; 0.001, HR = 0.79(0.74, 0.85) with rates at 12, 24, and 30 months of 0.86, 0.68, and 0.62%; and 0.83, 0.62, and 0.55%. Multivariate analyses for OS demonstrated similar prognostic factors in both year groups and were worse with advanced age, male sex, unmarried status, squamous histology, advanced stage and non-Hispanic white race. The LCSS was significantly better in AP than the BA group ( p &lt; 0.001, HR = 0.84 (0.7, 0.89) with rates at 12, 24, and 30 months of groups of 0.82,0.61, and 0.55%; and 0.80,0.56,and 0.48%. The prognostic factors for LCSS were the same in both group and included age, male sex, squamous histology, and advanced stage. The adjusted rates of 2C in 2018-2020 group were trending less than in 2015-2017 (HR = 0.80(0.63-1.03), p =0.07), largely driven by a reduction in smoking-related cancers (HR = 0.74(0.53-1.02, p= 0.07). The 2C rates at 12, 24, and 30 months were 1.0, 2.7, and 3.5% in the 2015-2017 and 0.9, 1.6, and 1.9% in 2018-2020 groups. MVA significant risk factors for 2Cs were age, history of previous cancer, male sex, and squamous histology in the BA group, but no factors were significant for 102 second cancers in the AA group. Conclusions: In the years after durvalumab's approval, there was a significant benefit in terms of overall survival and lung cancer specific survival, but prognostic factors remained similar. In addition to the OS/LCSS benefit, durvalumab's approval was associated with a strong trend for reducing the incidence of second cancers, especially in those with previous smoking related cancers.

Cancer Incidence After Diagnosis of Abdominal Aortic Aneurysm-Brief Report.

Epidemiological and mechanistic data support a potential causal link between cardiovascular disease (CVD) and cancer. Abdominal aortic aneurysms (AAAs) represent a common form of CVD with at least partially distinct genetic and biologic pathogenesis from other forms of CVD. The risk of cancer and how this risk differs compared with other forms of CVD, is unknown among AAA patients. We conducted a retrospective cohort study using the IBM MarketScan Research Database to test whether individuals with AAA have a higher cancer risk independent of traditional shared risk factors. All individuals ≥18 years of age with ≥36 months of continuous coverage between 2008 and 2020 were enrolled. Those with potential Mendelian etiologies of AAA, aortic aneurysm with nonspecific anatomic location, or a cancer diagnosis before the start of follow-up were excluded. A subgroup analysis was performed of individuals having the Health Risk Assessment records including tobacco use and body mass index. The following groups of individuals were compared: (1) with AAA, (2) with non-AAA CVD, and (3) without any CVD. The propensity score-matched cohort included 58 993 individuals with AAA, 117 986 with non-AAA CVD, and 58 993 without CVD. The 5-year cumulative incidence of cancer was 13.1% (12.8%-13.5%) in participants with AAA, 10.1% (9.9%-10.3%) in participants with non-AAA CVD, and 9.6% (9.3%-9.9%) in participants without CVD. Multivariable-adjusted Cox proportional hazards regression models found that patients with AAA exhibited a higher cancer risk than either those with non-AAA CVD (hazard ratio, 1.28 [95% CI, 1.23-1.32]; P<0.001) or those without CVD (hazard ratio, 1.32 [95% CI, 1.26-1.38]; P<0.001). Results remained consistent after excluding common smoking-related cancers and when adjusting for tobacco use and body mass index. Patients with AAA may have a unique risk of cancer requiring further mechanistic study and investigation of the role of enhanced cancer screening.

Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study.

The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. We evaluated the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors. The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs.

Abstract 2016: Prior Diagnosis Of An Abdominal Aortic Aneurysm Is Associated With An Elevated Risk Of Subsequent Cancer Diagnosis

Background: Epidemiological and mechanistic evidence suggests a potential causal link between cardiovascular disease (CVD) and cancer. Abdominal aortic aneurysms (AAA), a prevalent form of CVD with distinct genetic and biological etiologies, lack clarity regarding cancer risk compared to other CVD types. We conducted a retrospective cohort study using the IBM MarketScan Research Database to investigate whether AAA individuals face an increased cancer risk independent of traditional shared risk factors. Methods: Enrolling individuals aged ≥18 with ≥36 months of continuous coverage between 2008 and 2020, we excluded those with potential Mendelian AAA etiologies, aortic aneurysms with nonspecific anatomic location, or pre-follow-up cancer diagnoses. A subgroup analysis was performed including individuals with Health Risk Assessment records that included smoking status and BMI. We compared three groups: 1) AAA, 2) non-AAA CVD, and 3) no-CVD. Results: The propensity score-matched cohort comprised 68,269 AAA, 136,538 non-AAA CVD, and 136,538 no-CVD individuals. The 5-year cumulative incidence of any cancer was 10.0% (9.7 - 10.3%) in AAA, 7.4% (7.2 - 7.6%) in non-AAA CVD, and 7.4% (7.2 - 7.5%) in no CVD. Time-dependent multivariable-adjusted Cox proportional hazards regression models revealed AAA patients had a higher cancer risk than non-AAA CVD (HR: 1.32; 95% CI: 1.28-1.37; p-value: &lt;0.001) or no CVD (HR: 1.37; 95% CI: 1.32-1.44; p-value: &lt;0.001). Results were consistent after excluding common smoking-related cancers and when adjusting for smoking status and BMI in a subgroup analysis. Conclusions: AAA patients may face a uniquely elevated cancer risk, warranting further mechanistic study and enhanced cancer screening investigations.

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Smoking-associated gene expression alterations in nasal epithelium reveal immune impairment linked to lung cancer risk

Background Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to modifiable lifestyle risk in the form of tobacco smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, 40% of which occur more than 15 years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk remain unclear. We thus set out to examine whether risk stratification in the clinic and in the general population can be improved upon by the addition of genetic data and to explore the mechanisms of the persisting risk in former smokers.Methods We analysed transcriptomic data from accessible airway tissues of 487 subjects, including healthy volunteers and clinic patients of different smoking statuses. We developed a computational model to assess smoking-associated gene expression changes and their reversibility after smoking is stopped, comparing healthy subjects to clinic patients with and without lung cancer.ResultsWe find persistent smoking-associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune- and interferon-related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier.ConclusionsOur results provide initial evidence for germline-mediated personalized smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.

152 Integrated Clinical Genomic Analysis Reveals Xenobiotic Metabolic Genes are Downregulated in Meningiomas of Current Smokers

INTRODUCTION: Meningiomas are the most common primary intracranial tumor. We sought to identify clinical drivers of different molecular changes in meningioma. As such, clinical and genomic consequences of smoking in patients with meningiomas remain unexplored. METHODS: 88 tumor samples were analyzed. Whole exome sequencing (WES) was used to assess somatic mutation burden. RNA sequencing data was used to identify differentially expressed genes (DEG) and genes sets (GSEA). RESULTS: Fifty-seven patients had no history of smoking, thirty-one patients had history of ever smoking. Smokers were less likely to present with headache (p = 0.045) or have incidentally discovered meningiomas (p = 0.049). WES revealed no difference in canonical mutation burden. Smokers had increased mutation rate in KRTAP1-3, RECQL4, PTPRT, and PLB1 compared to never smokers (p &lt; 0.05). Mutational signature from smokers showed disrupted DNA mismatch repair (cosine-similarity = .784). DEG analysis of current smokers as compared to past or never smokers revealed the xenobiotic metabolic genes UGT2A1 and UGT2A2 were both significantly downregulated in current smokers compared to past (Log2FC = -3.97, padj = 0.0347 and Log2FC = -4.18, padj = 0.0304) and never smokers (Log2FC = -3.86, padj = 0.0235 and Log2FC = -4.20, padj = 0.0149). GSEA analysis of current smokers showed downregulation of xenobiotic metabolism and enrichment for G2M checkpoint, E2F targets, and mitotic spindle compared to past and never smokers (FDR &lt;25% each). CONCLUSIONS: There are limited differences in the clinical course of meningioma patients who smoke. There is no difference in burden of canonical mutations in meningiomas from patients who smoke, but differential mutation in several novel meningioma genes is identified. Mutational signatures in meningiomas from smokers show disrupted DNA mismatch repair. Meningiomas from current smokers demonstrate downregulation of xenobiotic metabolic enzymes UGT2A1 and UGT2A2, which are downregulated in other smoking related cancers. Taken together, our demonstrate novel alterations in meningioma molecular biology in response to systemic carcinogens.

Abstract 3452: Senescence-associated secretory phenotype (SASP) aging index is associated with cancer risk in the Atherosclerosis Risk in Communities (ARIC) Study

Abstract Background: The accumulation of senescent cells, which release SASP proteins damaging neighboring cells, contributes to aging and age-related diseases, such as cancer. Therefore, SASP proteins could be used as biomarkers for individuals’ aging process, but no studies have tested if SASP protein-based aging index is associated with cancer risk. We created a SASP-aging index based on the 72 SASP proteins reported in Tanaka et al. [2018] and examined its association with cancer risk in the ARIC study. Methods: ARIC is an ongoing cohort of White and Black females and males initiated in 1987, followed for cancer until 2015 (median follow-up=17.3 yrs). At Visit 2 (1990-92), 5000 plasma proteins were measured using SomaScan – an aptamer-based assay in 10,834 participants (aged 46-70 yrs, 55% female, 76% White): 3,347 participants developed cancer during follow-up and 7,487 participants stayed cancer-free. In the training set of 67% randomly selected cancer-free participants, we constructed the SASP-aging index by applying Ridge regression to train the 72 SASP proteins against chronological age. The SASP-aging index was validated in the remaining 33% of cancer-free participants (test set). We calculated age acceleration as residuals after regressing the SASP-aging index on age in participants after excluding the training set. We used Cox proportional hazards regression to estimate hazard ratio (HR) and 95% confidence intervals (CI) for the risk of any type of cancer per 5 years increase in age acceleration, employing Barlow’s method [1994] to account for the exclusion of the training set. HR was adjusted for age, sex, race, center, education, BMI, smoking status, alcohol intake, aspirin use, diabetes, and eGFR. We also estimated HRs for obesity-related, smoking-related, and the most common cancers (breast, prostate, colorectal, and lung). Results: In the test set, Pearson correlation coefficient between the SASP-aging index and age was 0.50. Age acceleration was significantly associated with the risk of any type of cancer [HR (95% CI) per 5 years=1.21 (1.08-1.36)]. There was a suggestion of a higher HR for any type of cancer in females [1.26 (1.07-1.48)] than males [1.18 (1.00-1.39)] [p-interaction=0.08], but HRs were similar across race and smoking status [p-interaction&amp;gt;0.50]. Age acceleration was significantly associated with the risk of obesity-related cancers [1.36 (1.20-1.54)]. A significant association was also found with smoking-related cancers [1.43 (1.24-1.65)] and this association remained significant even among never smokers [1.39 (1.07- 1.82)]. Age acceleration was also significantly associated with colorectal [1.34 (1.03-1.75)] and lung cancer risk [1.63 (1.31-2.02)] but not with breast or prostate cancer risk. Conclusion: SASP protein-based aging index shows promise as a potential biomarker for cancer risk. Funding: NHLBI, NCI, NPCR Citation Format: Shuo Wang, Zexi Rao, Anne H. Blaes, Josef Coresh, Corinne E. Joshu, James S. Pankow, Bharat Thyagarajan, Peter Ganz, Elizabeth A. Platz, Weihua Guan, Anna Prizment. Senescence-associated secretory phenotype (SASP) aging index is associated with cancer risk in the Atherosclerosis Risk in Communities (ARIC) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3452.

A unique circ_0067716/EIF4A3 double-negative feedback loop impacts malignant transformation of human bronchial epithelial cells induced by benzo(a)pyrene

Benzo(a)pyrene as a pervasive environmental contaminant is characterized by its substantial genotoxicity, and epidemiological investigations have established a correlation between benzo(a)pyrene exposure and the susceptibility to human lung cancer. Notably, much research has focused on the link between epigenetic alterations and lung cancer induced by chemicals, although circRNAs are also emerging as relevant contributors to the carcinogenic process of benzo(a)pyrene. In this study, we identified circ_0067716 as being significantly upregulated in response to stress injury and downregulated during malignant transformation induced by benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE) in human bronchial epithelial cells. The observed differential expression of circ_0067716 in cells treated with BPDE for varying durations suggests a strong correlation between this circRNA and BPDE exposure. The tissue samples of lung cancer patients also suggest that a lower circ_0067716 expression is associated with BPDE-DNA adduct levels. Remarkably, we demonstrate that EIF4A3, located in the nucleus, interacts with the flanking sequences of circ_0067716 and inhibits its biogenesis. Conversely, circ_0067716 is capable of sequestering EIF4A3 in the cytoplasm, thereby preventing its translocation into the nucleus. EIF4A3 and circ_0067716 can form a double-negative feedback loop that could be affected by BPDE. During the initial phase of BPDE exposure, the expression of circ_0067716 was increased in response to stress injury, resulting in cell apoptosis through the involvement of miR-324-5p/DRAM1/BAX axis. Subsequently, as cellular adaptation progressed, long-term induction due to BPDE exposure led to an elevated EIF4A3 and a reduced circ_0067716 expression, which facilitated the proliferation of cells by stabilizing the PI3K/AKT pathway. Thus, our current study describes the effects of circ_0067716 on the genotoxicity and carcinogenesis induced by benzo(a)pyrene and puts forwards to the possible regulatory mechanism on the occurrence of smoking-related lung cancer, providing a unique insight based on epigenetics.

Identification of prognostic biomarkers of smoking-related lung cancer.

The early diagnosis and effective prognostic treatment measures for lung cancer are still limited, leading to a 5-year survival rate of less than 15% for these patients. Smoking is one of the causes of lung cancer, but it is not the initial carcinogenic factor. It is not clear what specific mechanism cigarette induces lung cancer, and there is a lack of research on the relationship between related genes and the prognosis of patients with smoking lung cancer. The objective of this study was to provide new theoretical evidence and potential therapeutic targets for the mechanisms of smoking-related lung cancer formation. The gene expression profile data from the GSE12428 dataset which includes 63 lung cancer and normal tissue pairs were downloaded from the Gene Expression Omnibus (GEO) database, and data from smokers with lung cancer [both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC)] from The Cancer Genome Atlas (TCGA) database were analyzed. The differential genes in smokers with lung cancer were screened using the linear model for microarray data via R software. The differential gene enrichment analysis was performed using the online analysis software Database for Annotation, Visualization and Integrated Discovery (DAVID). The expression levels of differential genes and their correlation with patient tumor clinical stage were analyzed using gene expression profiling interactive analysis (GEPIA). The overall survival rate was analyzed using Kaplan-Meier curves. In the GSE12428 dataset, 225 upregulated genes and 565 downregulated genes were identified in cancer tissues; based on smoking status, 1 upregulated gene and 4 downregulated genes were identified. Among smokers who also had lung cancer, 4 genes were downregulated, namely CSH1, BPIFA1, SLPI, and SCGB3A1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these genes were mainly associated with biological functions such as antibacterial response, humoral immune response, and response to external stimuli. Among them, BPIFA1, SLPI, and SCGB3A1 expression was decreased in lung cancer tissues, with SCGB3A1 showing significant differences. Additionally, high expression of SCGB3A1 was associated with favorable prognosis in patients with lung cancer. Three genes BPIFA1, SLPI and SCGB3A1, were identified as being associated with smokers with lung cancer, with SCGB3A1 showing a close correlation with patient prognosis. These findings provide potential new targets for the treatment of lung cancer. Certainly, this study needs to more investigate the mechanism of these genes regulation.

Physician-brief advice for promoting smoking cessation among cancer patients on treatment in low and middle-income countries: a scoping review

IntroductionPhysician-brief advice has been utilized in high-income countries to promote smoking cessation among cancer patients. Empirical evidence on its effectiveness among cancer patients in low and middle-income countries (LMICs) is lacking. The gap could be due to inadequate training, and competing healthcare priorities, leading to insufficient implementation of targeted smoking cessation interventions in oncology settings. We undertook this scoping review to determine if physician-brief advice is effective in promoting smoking cessation among cancer patients in LMICs.MethodsWe conducted a literature search of all relevant articles across five databases: Cochrane Central Register of Controlled Trials, Cochrane Library (Tobacco Addiction Group trials), World Conference on Lung Cancer proceedings, PubMed, and Google Scholar up to November 2023, using pre-defined inclusion criteria and keywords. The study population was cancer survivors in LMICs, the intervention was smoking cessation advice by a physician in a clinic or oncology center during a consultation, and the outcome was the effect of smoking cessation programs in discontinuing smoking among cancer survivors in LMICs.ResultsOverall, out of every 10 cancer patients in LMICs, about seven were smokers, and one-half had received physician-brief advice for smoking cessation. Physician-brief advice was more likely to be delivered to patients with smoking-related cancer (Cohen’s d = 0.396). This means that there is a noticeable difference between patients with smoking-related cancer compared to those with cancer unrelated to smoking. Smoking cessation failure was due to the inability to cope with the symptoms of withdrawal, missed smoking cessation clinic visits, mental health disorders, limited time and resources, and minimal patient-physician contact.ConclusionThere is very little literature on the frequency of use or the efficacy of physician-brief advice on smoking cessation in LMICs. The literature suggests that cancer patients in LMICs have low self-efficacy to quit smoking, and smoking cessation is rarely part of cancer care in LMICs. Physicians in LMICs should be trained to use motivational messages and good counseling techniques to improve smoking cessation among cancer patients. Policymakers should allocate the resources to implement physician-brief advice and design training programs for physicians focusing on physician-brief advice tailored to cancer patients.

Lung cancer in patients who have never smoked - an emerging disease.

Lung cancer is the most common cause of cancer-related deaths globally. Although smoking-related lung cancers continue to account for the majority of diagnoses, smoking rates have been decreasing for several decades. Lung cancer in individuals who have never smoked (LCINS) is estimated to be the fifth most common cause of cancer-related deaths worldwide in 2023, preferentially occurring in women and Asian populations. As smoking rates continue to decline, understanding the aetiology and features of this disease, which necessitate unique diagnostic and treatment paradigms, will be imperative. New data have provided important insights into the molecular and genomic characteristics of LCINS, which are distinct from those of smoking-associated lung cancers and directly affect treatment decisions and outcomes. Herein, we review the emerging data regarding the aetiology and features of LCINS, particularly the genetic and environmental underpinnings of this disease as well as their implications for treatment. In addition, we outline the unique diagnostic and therapeutic paradigms of LCINS and discuss future directions in identifying individuals at high risk of this disease for potential screening efforts.

Association between ambient exposure to PM2.5 and upper aerodigestive tract cancer in Los Angeles.

Fine particulate matter (PM2.5 ) contains carcinogens similar to those generated by tobacco smoking, which may increase the risks of developing smoking-related cancers, such as upper aerodigestive track (UADT) cancers, for both smokers and never-smokers. Therefore, it is imperative to understand the relation between ambient PM2.5 exposure and risk of UADT cancers. A population-based case-control study involving 565 incident UADT cancer cases and 983 controls was conducted in Los Angeles County from 1999 to 2004. The average residential PM2.5 concentration 1 year before the diagnosis date for cases and the reference date for controls was assessed using a chemical transport model. The association between ambient PM2.5 and the UADT cancers was estimated by unconditional logistic regression, adjusting for confounders at the individual and block-group level. Stratified analyses were conducted by sex, tobacco smoking status and UADT subsites. We also assessed the interaction between PM2.5 and tobacco smoking on UADT cancers. PM2.5 concentrations were associated with an elevated odds of UADT cancers (adjusted odds ratio = 1.21 per interquartile range [4.5 μg/m3 ] increase; 95% confidence interval: 1.02, 1.44). The association between PM2.5 and UADT cancers was similar across UADT subsites, sex and tobacco smoking status. The interaction between PM2.5 and tobacco smoking on UADT cancers was approximately additive on the odds scale. The effect estimate for PM2.5 and UADT cancers was similar among never smokers. Our findings support the hypothesis that exposure to PM2.5 increases the risk of UADT cancers. Improvements in air quality may reduce the risk of UADT cancers.

Smoking cessation as a preventative measure of cancer: a systematic review

Background: Tobacco smoking is a leading cause of preventable cancer worldwide. This systematic review aims to synthesize and evaluate the existing literature on the relationship between smoking cessation, smoking reduction, and the risk of cancer, with a particular focus on lung cancer. Methods: A systematic search of electronic databases was conducted to identify relevant studies published up to the knowledge cutoff date in September 2021. Eight studies meeting the inclusion criteria were selected for analysis. These studies encompassed diverse populations and methodologies, including cohort studies and population- based investigations. Results: The findings reveal a consistent pattern across the included studies. Smoking cessation emerged as a highly effective strategy for reducing the risk of cancer, particularly lung cancer. Even individuals who quit smoking later in life experienced a substantial decrease in their cancer risk. Additionally, smoking reduction, although less effective than cessation, demonstrated a noteworthy impact, especially among heavy smokers. Reduction in the number of cigarettes smoked per day was associated with a decreased risk of all cancer, smoking-related cancer, and lung cancer. The results of this systematic review underscore the critical importance of smoking cessation as a primary strategy for mitigating cancer risk, aligning with broader public health objectives to reduce tobacco-related harm. While cessation remains the gold standard, smoking reduction can offer a pragmatic approach for those who are unable to quit immediately, particularly heavy smokers. The review also highlights the potential for personalized interventions based on age, smoking history, and histologic subtype to optimize smoking cessation efforts. Conclusion: Smoking cessation and reduction represent crucial strategies for preventing cancer, particularly lung cancer. Public health campaigns and clinical interventions should prioritize smoking cessation support, emphasizing the long-term benefits of remaining smoke-free. By promoting these measures, we can significantly reduce the burden of tobacco-related cancers and improve public health outcomes. Further research is needed to explore the long- term effects of smoking behavior changes on cancer risk, considering diverse populations and histologic subtypes.

A fractional mathematical model for assessing cancer risk due to smoking habits

This article presents and analyzes a mathematical model for smoking-related cancer that involves fractional-order derivative with seven different compartments. The model uses the ABC fractional derivative to describe the transmission dynamics of cancer caused by the smoking habit. We employed the Adams-Bashforth-Moulton method to find the numerical and graphical results of the model and we achieved a good level of accuracy. The existence and uniqueness of the model solution were established using Banach's fixed-point theory. For stability, we investigated the steady state points and basic reproduction number of the system. Additionally, the model's stability was discussed using the Hyers-Ulam criterion. The two-dimensional (2D) and three-dimensional (3D) simulations were performed for the different compartments and for the various values of the fractional-order parameters.