Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression.

Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.

Urinary cotinine and exposure to passive smoke in children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V).

Passive smoking is a preventable and significant cause of many serious health problems, with children being particularly at risk. In the fifth German Environmental Survey (GerES V), conducted from 2014 to 2017, information reflecting the extent of passive smoke exposure in children and adolescents was collected by interview-based questionnaires and human biomonitoring (HBM) analyses of cotinine in urine from 2260 participants, aged 3-17 years. Based on these population-representative data, we describe current passive smoke exposure stratified by different subgroups and identify specific exposure determinants using multivariate logistic regression. The questionnaire data revealed that 42% of children and adolescents lived with at least one smoker in the household. Quantifiable concentrations of cotinine could be detected in 56% of the participants. The overall median concentration of cotinine was 0.2 µg/L, with children and adolescents of low socioeconomic status found to be a group particularly affected by passive smoke with higher cotinine concentrations (median = 1.2 µg/L). In the multiple analysis, the most significant predictor of cotinine levels derived from the questionnaire was passive smoking at home (odds ratio (OR) 13.07 [95CI: 4.65, 36.70]). However, parental smoking and passive smoking among friends and relatives could also be identified as independent factors influencing elevated cotinine levels. The comparison between the previous cycle GerES IV (2003-2006) on 3-14-year-olds and GerES V shows that tobacco smoke exposure of children decreased significantly. This decrease is likely an effect of extensive non-smoker protection laws being enforced 2007-2008 on federal and state level. This is reflected by a halving of urinary cotinine concentrations. Nevertheless, our results indicate that passive smoke is still a relevant source of harmful pollutants for many children and adolescents in Germany, and thus support the need for further efforts to reduce passive smoke exposure, especially in the private environment.

Lifestyle factors and lung cancer risk among never smokers in the Canadian Partnership for Tomorrow's Health (CanPath).

BACKGROUND: Although smoking is the primary risk factor for lung cancer, 15-25% of lung cancers occur in never smokers. Emerging evidence suggests lifestyle factors are associated with lung cancer risk, but few studies among never smokers exist. METHODS: A case-control study of never smokers within the Canadian Partnership for Tomorrow's Health was conducted. At recruitment, participants provided data on lifestyle, health history and sociodemographic factors. Incident lung cancers were identified through linkage with administrative health records. Cases (n = 190) were matched to controls (n = 760) on age, sex, and follow-up time. Logistic regression analyses, adjusted for matching factors and annual income, were used to identify associations between lifestyle factors and lung cancer risk. RESULTS: Consumption of < 5 servings of fruits and vegetables/day was associated with higher risk of lung cancer (OR 1.50, 95% CI 1.03-2.17). Short or long sleep (≤ 6 or > 9 h/night) was also associated with increased risk of lung cancer (OR 1.52, 95% CI 1.01-2.29). No associations were observed for obesity measures, alcohol consumption, or physical activity. CONCLUSION: Our findings provide evidence of a potential role between sleep, fruits and vegetable consumption, and lung cancer risk in a pan-Canadian, non-smoking population. However, the sample size is modest, and further investigation is needed.

Urinary polycyclic aromatic hydrocarbon excretion and regional body fat distribution: evidence from the U.S. National Health and Nutrition Examination Survey 2001-2016.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that may contribute to the etiology of obesity. However, it is unclear whether PAHs from environmental sources are associated with regional body fat distribution, and whether the association varies across racial/ethnic groups who may have differential PAH exposure patterns. OBJECTIVES: To examine correlations between PAHs and body fat distribution, and potential racial/ethnic differences among U.S. adults. METHODS: Ten PAHs were measured in spot urine samples from 2691 non-smoking adults (age ≥ 20 years) in the NHANES 2001-2016. Dual-energy X-ray absorptiometry was used to measure fat mass percent (FM%). Partial Pearson correlation coefficients (r) with multivariable adjustment were used to assess PAH-FM% associations. RESULTS: In the total population, 1-naphthalene, 3-fluorene, and 1-pyrene were inversely correlated with total FM% or trunk FM% (adjusted r ranged: - 0.06 to - 0.08), while 2-naphthalene, 9-fluorene, and 4-phenanthrene were positively correlated with the FM% measurements (r: 0.07-0.11). PAH levels are highest among non-Hispanic Blacks, followed by Hispanics and Whites and some of the correlations were different by these races/ethnicities. Among non-Hispanic Whites, no PAH was correlated with FM%. In contrast, 9-fluorene was positively correlated with total FM% (r = 0.20) and trunk FM% (r = 0.22) among Blacks, and 4-phenanthrene was positively correlated with total FM% (r = 0.23) and trunk FM% (r = 0.24) among Hispanics (P-interaction: 0.010-0.025). DISCUSSION: In this US adult population, certain PAHs are significantly associated with higher body fat contents among non-Hispanic Blacks and Hispanics but not non-Hispanic Whites, suggesting that minority groups might be particularly susceptible to PAH's obesogenic effects or the effects of other factors that determine the PAH exposure levels. Alternatively, differences in body composition may contribute to differential PAH metabolism in minority groups. Future studies are warranted to explore the racial/ethnic disparity in PAH exposures, drivers of these exposure differences, and mechanisms through which PAHs may influence body composition by races/ethnicities.

Urinary Metals, Arsenic, and Polycyclic Aromatic Hydrocarbon Exposure and Risk of Self-reported Emphysema in the US Adult Population.

PURPOSE: Metal and chemical exposure can cause acute and chronic respiratory diseases in humans. The purpose of this analysis was to analyze 14 types of urinary metals including mercury, uranium, tin, lead, antimony, barium, cadmium, cobalt, cesium, molybdenum, manganese, strontium, thallium, tungsten, six types of speciated arsenic, total arsenic and seven forms of polycyclic aromatic hydrocarbons (PAHs), and the link with self-reported emphysema in the US adult population. METHODS: A cross-sectional analysis using the 2011-2012, 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey datasets was conducted. A specialized weighted complex survey design analysis package was used in analyzing the data. Multivariate logistic regression models were used to assess the association between urinary metals, arsenic, and PAHs and self-reported emphysema among all participants and among non-smokers only. Models were adjusted for lifestyle and demographic factors. RESULTS: A total of 4,181 adults were analyzed. 1-Hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene, 1-hydroxypyrene, and 2 & 3-hydroxyphenanthrene were positively associated with self-reported emphysema. Positive associations were also observed in cadmium and cesium with self-reported emphysema. Among non-smokers, quantiles among 2-hydroxynaphthalene, arsenocholine, total urinary arsenic, cesium, and tin were associated with increased odds of self-reported emphysema. Quantiles among 1-hydroxyphenanthrene, cadmium, manganese, lead, antimony, thallium, and tungsten were associated with an inverse relationship with self-reported emphysema in non-smokers. CONCLUSION: The study determined that six types of urinary PAHs, cadmium, and cesium are positively associated with self-reported emphysema. Certain quantiles of 2-hydroxynaphthalene, arsenocholine, total urinary arsenic, cesium, and tin are positively associated with self-reported emphysema among non-smokers.

Oral cavity squamous cell carcinomas in patients with no identified risk factors: Feeling like an outsider.

OBJECTIVES: Head and neck squamous cell carcinomas (HNSCCs) mainly affect smokers and drinkers. However, oral cavity squamous cell cancers (OCSCCs) are increasingly affecting patients with no identified risk factors (NIRFs). This study aimed at characterising their experience of the disease. METHODS: Qualitative study based on semi-structured interviews of 20 survivors of OCSCC with NIRF. Methods used in grounded theory approach were applied. RESULTS: Patients with NIRF had a similar experience to that of patients with risk factors regarding treatments. The absence of identified causes led to stigma and led the patients to distance themselves, both from the stereotypic HNSCC cancer patient and the identity as a cancer patient. Furthermore, having no identified risk factors seemed to reinforce the fear of recurrence. CONCLUSION: This study is the first to address key gaps in knowledge regarding patients with NIRF having survived OCSCC. Their experience is similar to that of patients with orphan diseases. Owing to confrontation with other patients and the repeated questions of caregivers about tobacco/alcohol consumption, these patients felt stigmatised during their treatment. OCSCC patients with NIRF may benefit from guidance and support on how to engage in prevention.

Oral tongue squamous cell carcinomas in young patients according to their smoking status: a GETTEC study.

BACKGROUND: Incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing, especially in young adults, despite decreasing tobacco and alcohol consumption. METHODS: This multicentric retrospective study of 185 young adults with OTSCC (median follow-up 43 months), investigated risk factors, tumour characteristics and oncological outcomes according to the smoking status. RESULTS: Overall, 38% of patients were smokers (S). Non-smokers (NS) were significantly younger than S. Sex ratios were 1.1 for N and 1.8 for S. NS patients were less frequently cannabis or alcohol users than S, but were more likely to have a history of leukoplakia. Second primaries were observed in NS (4.4%) and in S (12.7%). Despite more frequent local relapse in NS (p = 0.018), there was no difference in diagnostic stage and overall survival between groups. CONCLUSION: OTSCC affects differently young S and NS patients suggesting the existence of a specific clinical entity of OTSCC in non-smoking young adults.

The effect of preoperative smoking and smoke cessation on wound healing and infection in post-surgery subjects: A meta-analysis.

A meta-analysis was performed to evaluate the preoperative smoking and smoke cessation on wound healing and infection in post-surgery subjects. A systematic literature search up to January 2022 incorporated 11 trials involving 218 567 subjects after post-surgery at the beginning of the study; 176 670 were smoke cessation or non-smokers, and 41 897 were smokers. Statistical tools like the dichotomous method were used within a random or fixed-influence model to establish the odds ratio (OR) with 95% confidence intervals (CIs) to evaluate the influence of preoperative smoking and smoke cessation on wound healing and infection in post-surgery subjects. Smoke cessation or non-smokers had significantly lower postoperative wound healing problems (OR, 0.59; 95% confidence interval, 0.43-0.82, P < .001), and surgical site wound infection (OR, 0.74; 95% CI, 0.63-0.87, P < .001) compared with smokers in post-surgery subjects. Smoke cessation or non-smokers had significantly lower postoperative wound healing problems, and surgical site wound infection compared with smokers in post-surgery subjects. Furthermore, evidence is needed to confirm the outcomes.

Effects of transdermal nicotine delivery on cognitive outcomes: A meta-analysis.

OBJECTIVE: By the association of nicotinic acetylcholine receptors in the brain, nicotine in the therapeutic window lowers neuronal damage and raises protective factors. These data, however, are contradicted by other findings. Here, we assessed the effects of transdermal nicotine administration on cognitive functions in healthy non-smoker adults by systematic review and meta-analysis of clinical trials. METHODS: We included reports of clinical trials comparing the effects of nicotine patches with placebo in healthy non-smoking adults. The main outcome was the impact of nicotine patches on overall cognitive function with a focus on attention and memory. Standard meta-analytic and statistical methods measured the effect of transdermal nicotine compared with placebo patches. RESULTS: We included 31 publications involving 978 subjects. Nicotine patches boosted cognitive function in healthy adults (0.233 SMD, 95%CI, 0.111-0.355, p < .001). Overall heterogeneity of the studies was found to be modest (Ï°2  = 68.24, T2  = 0.07, I2  = 50.17%, p < .001). Also, nicotine patches improved attention (0.231 SMD, 95%CI, 0.106-0.356, p < .001). We found the inter-study heterogeneity to be low (Ï°2  = 40.95, T2  = 0.03, I2  = 34.07%, p = .042). Further, the enhancement of memory by transdermal nicotine did not reach statistical significance in normal subjects (0.270 SMD, 95% CI, -0.293-0.833, p = .347). Also, high inter-study heterogeneity was found among studies (Ï°2  = 27.25, T2  = 0.43, I2  = 77.98%, p < .001). CONCLUSION: The meta-analysis showed that transdermal nicotine had statistically significant positive effects on attention, and non-significant effects on memory, in healthy non-smoking adults. The results encourage further studies of the therapeutic potential of nicotine patches in disorders of cognition.

Fixed-dose combination of three drugs, i.e. LABA/LAMA/ICS for COPD: Results of a real-world study from India.

BACKGROUND: The use of triple therapy with inhaled corticosteroids, long-acting beta-agonist and long-acting antimuscarinics has been shown to be beneficial in COPD patients who continue to have symptoms and exacerbations, despite receiving dual bronchodilator combinations. This study assessed the real-world effectiveness and safety of once-daily, fixed-dose combination of Tiotropium/Formoterol/Ciclesonide (TFC) (18 mcg/12 mcg/400 mcg) via dry powder inhaler (DPI) or metered dose inhaler (MDI) in patients with COPD. PATIENTS AND METHODS: In this 24-week, open-label, prospective, non-comparative, multicentre, real-world study, COPD patients requiring triple therapy as judged by their physician, were enrolled. The primary endpoint was mean change from baseline in pre-dose Forced Expiratory Volume in 1 s (FEV1) at week 24. Pre and post-dose (30 min) FEV1, Forced Vital capacity (FVC), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) score and safety were also evaluated. A post-hoc analysis was conducted to evaluate the efficacy of the triple drug combination among smoker and non-smoker COPD patients. RESULTS: Out of the 297 patients enrolled [mean age 61 ± 10 years; 84.8% males; 55.2% smokers and post-dose FEV1 (% predicted) 39 ± 16%], 253 completed the study. Mean change in pre-dose FEV1 from baseline to week 24 increased significantly after administering the triple drug combination [580 ± 600 mL, 95% CI (510, 650 mL), p < 0.0001]. The increase in the pre-dose FEV1 was significant at all time points (p < 0.0001). Similar improvements were seen in pre-dose FVC, post-dose FEV1 and post-dose FVC across all time points. CAT scores and the proportion of patients with improved mMRC score improved at all visits. The post-hoc analysis showed that TFC significantly increased pre-dose FEV1 both among smokers [mean change 200 ± 430 mL, 95% CI (130, 270 mL), p < 0.0001] as well as non-smokers [990 ± 470 mL, 95% CI (900, 1070 mL), p < 0.0001] at week 24. This difference was significant from week 12 onwards. Mean change in pre and post-dose FEV1 and FVC was significant across all visits between the two groups. At week 24, CAT score reduced significantly from baseline (overall: -6.6 ± 6.07; smokers: -5.17 + 6.96; non-smokers: 8.06 ± 4.44; all p < 0.0001). The mean difference between the two groups was 2.88 (p < 0.0001) at week 24. TFC was well tolerated. CONCLUSION: In this real world, multicentre study in India, TFC significantly improved lung function, symptoms and quality of life among all patients with COPD, but the effect was more pronounced among non-smoker COPD patients.

Pulmonary mucoepidermoid carcinoma arising in a patient with Kartagener syndrome.

BACKGROUND: Kartagener syndrome, an autosomal recessive disorder with a triad of chronic sinusitis, bronchiectasis, and situs inversus, is characterized by recurrent respiratory tract infections and chronic inflammation of the lung. Information on comorbidities other than infections in patients with Kartagener syndrome is currently limited. CASE PRESENTATION: A 39-year-old, non-smoking female was diagnosed with Kartagener syndrome and admitted to Saitama Medical Center, Jichi Medical University, Japan. Computed tomography revealed an endobronchial massive shadow at the ostial site of the right upper lobe bronchus with atelectasis of the right upper lobe. The mass was surgically resected and pathologically diagnosed as mucoepidermoid carcinoma. The lesion had no vascular invasions and no metastases to the lungs or lymph nodes. The surgical margin was negative for carcinoma. Following surgery, the patient has been in good condition. CONCLUSIONS: The present case showed different clinicopathological characteristics from those previously reported in cases of Kartagener syndrome complicated by carcinoma. To the best of our knowledge, this is the first reported case of a young, non-smoking female with comorbid Kartagener syndrome and pulmonary mucoepidermoid carcinoma. This case report may provide a new perspective on the complications of Kartagener syndrome.

Differential impact of CX3CL1 on lung cancer prognosis in smokers and non-smokers.

CX3CL1 is a unique chemokine, expressed in both soluble and membrane bound forms, which mediates different biological activities. Recent studies have revealed the potential of CX3CL1 signaling pathway as a target for the treatment of inflammation and cancer. The correlation between expression of CX3CL1 and prognosis of patients varies among cancers. In this study, based on CX3CL1 immunohistochemistry in non-small cell lung cancer, CX3CL1 levels were positively associated with cancer stage (Pearson chi-square, P = 0.048) and lymph node status (P = 0.033). Interestingly, survival effects of CX3CL1 were only observed in patients with smoking history and adenocarcinoma (AD, log rank, P = 0.027), but not in patients with squamous cell carcinoma (SQ). The median survival time of patients with smoking history and low level CX3CL1 expressing AD was 1538 days, while that of patients with smoking history and high level CX3CL1 expressing AD was 396 days. Cox regression models showed adverse effects of high CX3CL1 levels only in AD patients with smoking history (hazard ratio = 3.01, p = 0.034), but not in AD patients without smoking history or in SQ patients with smoking history. The results of this study suggest that CX3CL1 plays different roles in lung tumorigenesis in smokers and non-smokers, and different CX3CL1-based therapeutic strategies are needed depending on patient smoking status and tumor type. Furthermore, high level of CX3CL1 expression enhances nodal metastasis by activating JNK & MMP2/MMP9 activity in lung cancer cells.

Non-Small Cell Lung Carcinoma in Women: A Retrospective Cohort Study in Indonesia.

BACKGROUND: the increasing incidence of lung cancer in female patients has been observed in Indonesia. Lung cancer in female might have different biology process than male, but it has never been evaluated in Indonesia. This study aimed to know characteristics and survival of female patients with non-small-cell lung carcinoma (NSCLC) in Dharmais National Cancer Centre Hospital. METHODS: a retrospective cohort study was performed among NSCLC female patients in Dharmais Cancer Hospital (DCH) between January 2005 and December 2015. Survival analysis was done using the Kaplan-Meir estimation curve with proportional assumption test. Independent prognostic factors were analyzed using the Cox proportional hazard model with a hazard ratio (HR) and its 95% confidence interval (CI). RESULTS: a total of 956 NSCLC cases were retrieved during the study; 268 (28.0%) were female patients. Mean of age in female patients was 56.9 (11.87) years old. Among female patients, 21 (7.8%) were smokers, 244 (91.1%) had adenocarcinoma subtype, and 261 (98.0%) were in advanced stage (III-IV). Median survival was slightly longer in female than male patients (14.9 months vs. 12.2 months; log-rank p=0.055). Significant prognostic factors for survival were older age (>50 y.o) (HR = 0.681; 95% CI = 0.467 - 0.992; p= 0.045) and positive eGFR mutation (HR = 0.393; 95% CI = 0.251 - 0.615; p<0.001). CONCLUSION: female patients contributed to about 28% of all NSCLC cases. They were mostly non-smokers, have more adenocarcinoma histopathology and eGFR mutation. Survival tended to be longer in female than male patients. Age over 50 years and the presence of eGFR mutation were good prognostic factors to survival in female lung cancer patients.

Propensity score analysis of lung cancer risk in a population with high prevalence of non-smoking related lung cancer.

BACKGROUND: Lung cancer has been the leading cause of cancer-related mortality worldwide among both men and women in recent years. There is an increase in the incidence of nonsmoking-related lung cancer in recent years. The purpose of the present study was to investigate multiple potential risk factors for nonsmoking-related lung cancer among Asian Ethnic Groups. METHODS: We used a propensity score-mated cohort analysis for this study. We retrospectively review the medical record of 1975 asymptomatic healthy subjects (40 ~ 80 years old) who voluntarily underwent low-dose chest CT from August 2013 to October 2014. Clinical information and nodule characteristics were recorded. RESULTS: A propensity score-mated cohort analysis was applied to adjust for potential bias and to create two comparable groups according to family history of lung cancer. For our primary analysis, we matched 392 pairs of subjects with family history of lung cancer and subjects without history. Logistic regression showed that female gender and a family history of lung cancer were the two most important predictor of lung cancer in the endemic area with high prevalence of nonsmoking-related lung cancer (OR = 11.199, 95% CI = 1.444-86.862; OR = 2.831, 95% CI = 1.000136-8.015). In addition, the number of nodules was higher in subjects with family history of lung cancer in comparison with subjects without family history of lung cancer (OR = 1.309, 95% CI = 1.066-1.607). CONCLUSIONS: In conclusion, risk-based prediction model based on the family history of lung cancer and female gender can potentially improve efficiency of lung cancer screening programs in Taiwan.

GAB2 Amplification in Squamous Cell Lung Cancer of Non-Smokers.

Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015. Clinical characteristics were reviewed, and DNA was extracted from fresh frozen lung cancer specimens. All of copy number alterations from ArrayCGH were validated using The Cancer Genome Atlas (TCGA) copy number variation (CNV) data of lung SCC. We examined the frequency of copy number changes according to the smoking status (non-smoker [n = 8] or smoker [n = 11]). We identified 16 significantly altered regions from ArrayCGH data, three gain and four loss regions overlapped with the TCGA lung squamous cell carcinoma (LUSC) patients. Within these overlapped significant regions, we detected 15 genes that have been reported in the Cancer Gene census. We also found that the proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smokers patients and vice versa in both ArrayCGH and TCGA data. Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers.

Attitudes towards passive smoking at restaurants and effects of the provision of information: A comparison between smokers and non-smokers via a web survey.

Objectives　Our objectives were to conduct a web-based survey using adult participants to investigate 1) differences in attitudes towards smoking in the presence of non-smokers between smokers and non-smokers and 2) the potential impact of knowledge regarding the harmful effects of smoking and secondhand smoke (SHS) on smoker behavior in a restaurant.Method　Japanese smokers and non-smokers aged 20 to 69 were separately sampled and both groups were randomly allocated to either a knowledge group or a control group. The participants were asked to complete an online questionnaire to capture their attitudes and how they think they would behave in a restaurant where it was not clear whether smoking is prohibited or not. Data were analyzed using a t-test for numerical variables and a χ2 test for categorical variables. Logistic regression analysis was also conducted to elucidate the factors influencing the smoking behavior near non-smokers.Results　Overall, 2,157 participants were surveyed (smokers, n=1,084; non-smokers, n=1,073). Among smokers who intended to smoke in the restaurant, 24.8% answered that they would ask for permission from nearby persons before lighting up. However, only 2.8% of non-smokers had ever actually been asked for such permission. The percentage of smokers who would smoke in the restaurant was significantly lower in the knowledge group (16.4%) than the control group (22.8%). The most common reason for refraining from smoking was a lack of an ashtray on the table in both groups. Among the non-smokers, 37.4% of the knowledge group and 27.6% of the control group answered that they did not like nearby smoking. A multiple logistic regression analysis revealed that smoking in restaurants was significantly associated with nicotine dependence, household income, pregnancy, smoking place in the home, age, and SHS knowledge.Conclusion　This study suggested that most non-smokers do not inform smokers that they do not like nearby smoking. It was also found that smoking behaviors could be influenced by non-smokers' preference for nearby smoking and by environmental factors such as the presence of an ashtray on the table. Knowledge about the harmful effects of smoking and SHS may influence the attitudes and behavior towards nearby smoking among both smokers and non-smokers.

HPV prevalence and p16INKa overexpression in non-smoking non-drinking oral cavity cancer patients.

OBJECTIVE: Our aim was to compare HPV and p16INK4a (p16) expression and their influence on survival and prognosis in oral cavity squamous cell cancer (OCSCC), between non-smokers and non-drinkers (NSND) and smokers and drinkers (SD). SUBJECTS AND METHODS: Patients with OCSCC treated with surgery from 2000 to 2010 were included in the study. Patients who did not smoke at all or smoked less than 10 pack per years and did not drink alcohol on a daily basis were considered the NSND group. An equal number of SD were the control group. HPV presence was determined from paraffin-embedded blocks investigated by PCR analysis. p16 expression was evaluated with immunohistochemistry. RESULTS: The NSND group were mostly younger or older female patients with tongue or gingival cancers. p16 expression was significantly more frequent in NSND patients (27% vs 10%). Patients with stronger p16 expression had significantly worse survival, especially for tongue cancers (P = 0.026). In Cox multivariate analysis, both HPV and p16 expression carried a negative prognosis for NSND patients (P = 0.0351 and P = 0.0260). CONCLUSIONS: NSND are a specific population of OCSCC patients. In contrast to oropharyngeal cancer, HPV and p16 expression in OCSCC are negative predictive factors, especially in NSND patients.

Lung Cancer in Never Smokers.

Lung cancer is predominantly associated with cigarette smoking; however, a substantial minority of patients with the disease have never smoked. In the US it is estimated there are 17,000-26,000 annual deaths from lung cancer in never smokers, which as a separate entity would be the seventh leading cause of cancer mortality. Controversy surrounds the question of whether or not the incidence of lung cancer in never-smokers is increasing, with more data to support this observation in Asia. There are several factors associated with an increased risk of developing lung cancer in never smokers including second hand smoke, indoor air pollution, occupational exposures, and genetic susceptibility among others. Adenocarcinoma is the most common histology of lung cancer in never smokers and in comparison to lung cancer in smokers appears less complex with a higher likelihood to have targetable driver mutations.

Low/negative expression of DDX3 might predict poor prognosis in non-smoker patients with oral cancer.

OBJECTIVE: DDX3 has diverse biological functions in translation control, cell growth regulation, and tumor progression. Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide with a poor clinical prognosis. The impact of DDX3 expression in OSCC is seldom discussed. MATERIALS AND METHODS: Tumor tissues and adjacent normal tissues were obtained from 324 patients with OSCC. In this study, we used immunohistochemical staining methods to investigate the associations between DDX3 expression and the clinicopathological characteristics of OSCC. RESULTS: Low/negative DDX3 expression in tumor cells was significantly associated OSCC patient characteristics including male gender (P < 0.001), smoking (P < 0.001), alcohol consumption (P < 0.001), betel quid chewing (P = 0.002), poor relapse-free survival (P = 0.001), and poor overall survival (OS) (P = 0.001). Patients with low/negative DDX3 expression, and particularly non-smoker OSCC patients, had significantly worse OS as defined by the log-rank test (P = 0.020 for all cases; P = 0.008 for non-smoker patients). In non-smoker patients with OSCC, low/negative DDX3 expression in tumor cells was associated with poor prognosis (P = 0.024) and a 3.802-fold higher death risk, as determined by Cox regression. CONCLUSIONS: Low/negative DDX3 expression in tumor cells was significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in non-smoker patients with OSCC.

Comparative study of lung cancer between smokers and nonsmokers: A real-world study based on the whole population from Tianjin City, China.

INTRODUCTION: The purpose of this study was to examine the prevalence, clinical characteristics, and changing trends of non-smokers with lung cancer (LC) based on data from a population-wide cancer registry in northern China. METHODS: The study used LC incidence and follow-up data from 2010 to 2019 from the Cancer Registry System of Tianjin city, which included 82769 cases. Trends in the incidence and proportion of non-smokers with LC were examined by joinpoint regression analysis. Life table and Cox survival analyses were used to calculate the survival rates and compare the death hazard ratios (HRs) in different groups, respectively. RESULTS: Among the 82769 new diagnosis cases of LC during 2010 to 2019, there were 34589 (41.8%) current smokers, 14913 (18.0%) ex-smokers, 28123 (34.0%) non-smokers, and 5144 (6.2%) unknowns. The proportion of non-smokers changed slightly from 2010 (35.36%) to 2019 (36.87%) (annual percentage change, APC= -0.01%, p>0.05). This proportion declined in men (2010 vs 2019; 22.06% vs 20.66%) and increased in women (2010 vs 2019; 53.02% vs 62.35%), and in the 0-44 years age group it showed an upward trend from 2015 to 2019 (APC=4.82%, 95% CI: 1.8-7.9). Compared with smokers with LC, non-smokers with LC were predominantly females (64.15% vs 27.26%), had a predominantly adenocarcinoma histological subtypes (76.71% vs 42.22%), and had a 20% lower risk of death than smokers (HR=0.80; 95% CI: 0.78-0.81). CONCLUSIONS: The proportion of non-smokers with LC was relatively high in northern China, with an increasing trend in the proportion of females and younger age groups. Non-smokers with LC had different epidemiological and clinical characteristics compared with smokers with LC.