The benefits of smoking cessation on survival in cancer patients by integrative analysis of multi‐omics data

Abstract

Few studies have examined the association between smoking status (including former smokers) at diagnosis and overall survival among cancer patients. We aimed to assess the benefits of quitting smoking on cancer prognosis in cohorts of cancer patient smokers obtained from the Cancer Genome Atlas (TCGA) database. Hazard ratios (HR) were calculated to evaluate smoking behavior at cancer diagnosis (reformed smokers vs. current smokers) in association with overall survival using multivariate‐adjusted Cox regressions analysis. According to our analyses, quitting smoking was the independent protective factor for overall survival in lung squamous cell carcinoma (LUSC) (HR = 0.67, 95% CI = 0.48–0.94). Comprehensive analysis of multicomponent data across reformed and current smokers identified a total of 85 differential expressed genes (DEGs) affected by different modes of genetic and epigenetic regulation, potentially representing cancer drivers in smokers. Moreover, we provided a smoking‐associated gene expression signature, which could evaluate the true effect on prognosis with high power (HR = 1.70, 95% CI = 1.19–2.43, AUC = 0.65, 0.67, and 0.70 for 2‐, 3‐, and 5‐year survival, respectively). This signature was also applicable in other smoking‐related cancers, including bladder urothelial carcinoma (HR = 1.70, 95% CI = 1.01–2.88), cervical carcinoma (HR = 5.69, 95% CI = 1.37–23.69), head and neck squamous cell carcinoma (HR = 1.97, 95% CI = 1.41–2.76), lung adenocarcinoma (HR = 1.73, 95% CI = 1.16–2.57), and pancreatic adenocarcinoma (HR = 4.28, 95% CI = 1.47–12.47). In conclusion, this study demonstrates that quitting smoking at diagnosis decreases risk of death in cancer patients. We also provide a smoking‐associated gene expression signature to evaluate the effect of smoking on survival. Lastly, we suggest that smoking cessation could comprise a part of cancer treatment to improve survival rates of cancer patients.

A Novel Signature for Predicting Prognosis of Smoking-Related Squamous Cell Carcinoma

“…By plotting K-M curves, we found that current smokers had a worse prognosis than reformed smokers in most SCC cohorts, which was consistent with other studies (Li et al, 2020;Yang et al, 2020). Then, we found smoking-related genes and performed function analysis in LUSC, pointing out that HR was an important pathway of smoking to aggravate cancer.…”

“…To better predict the prognosis of each patient, we constructed a nomogram integrating risk scores, smoking status, and clinical information. As a practical tool to improve predictive accuracy, these methods have been applied in many studies on different cancers (Sun et al, 2020;Yang et al, 2020). The nomogram with different aspects of markers, including risk scores, smoking status, age, gender, and tumor stage, had high clinical application value, which might be a promising way to change clinical management (Birkhahn et al, 2007).…”

“…Cigarette smoke contains many carcinogens that can cause genomic alteration and break immunologic homeostasis (Li et al, 2018). Many studies have reported that smoking cessation can eliminate the physiological driving force of cancer development and improve the prognosis of SCC patients (Dobson Amato et al, 2015;Yavorski and Blanck, 2016;Yang et al, 2020). However, the underlying mechanism of smoking-induced SCC remains unclear in smoking-related SCC.…”

Association Between Alcohol Consumption and Risk of Bladder Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies

“…The association between modifiable lifestyles and the risk of neoplastic and chronic diseases of the genitourinary system has attracted researchers' attention for a long time (34)(35)(36)(37). And lifestyle interventions were found to improve clinical outcomes for cancer or chronic medical conditions, either directly or indirectly (34,(38)(39)(40). The bidirectional relationship between lifestyle factors and disease might be systemic and multifaceted, for which lifestyle interventions might have a positive impact on overall health in addition to optimizing the disease-specific outcomes (41,42).…”

Potential Autoimmunity of SARS CoV-2 Nucleic Acid-based Vaccination: What Should We Know?

“…Interestingly, quitting smoking at diagnosis was recently shown to decrease the risk of death in cancer patients [73], and quitting smoking was suggested to alleviate its impact in patients with pneumonia and other COVID-19 associated infections [66,68,74], thus a beneficial advice to quit smoking together with another to lose overweight and to control the blood glucose levels might also help to lower the chances of SARS CoV-2 adenovirus and RNA-based vaccine potential autoimmunity in those individuals.…”