Lung Cancer In Smokers Research Articles

Abstract PR006: Screening under-served populations by mobile low dose computerized tomography (LDCT) scans results in stage shift with potential cures: Time for a change in health policy?

Abstract Background: More than 60% of under-served patients with lung cancer first present with advanced/metastatic disease. Randomized trials have shown that LDCT of chest reduces lung cancer mortality but under-served populations have been excluded from these studies because of financial, geographic, insurance and access problems. We have tested the first mobile LDCT units and demonstrated improved access. We report a shift to earlier stage at diagnosis and potential cures in a large under-served population that includes African American, Hispanic/LatinX and Native American subjects. Methods: We developed two coaches fitted with portable 32 slice low-dose CT scanners to screen uninsured and under-served heavy smokers for lung cancer in an IRB-approved program ("The Oncologist", 2019). All films were reviewed by a central panel (using LUNG RADS protocol). Medicare patients were excluded because their insurance covers LDCT lung screening (but it should be noted that the elderly population is at increased risk for lung cancer, leading to a negative case selection bias). Results: We initially screened 1200 uninsured/under-insured subjects, mean age 61 years (range 55-64), with average pack year history of 47.8 (range 30- >150); 61% male; 18% Black, 3% Hispanic/LatinX, <1% Native American; 78% rural. We found 97 pts with LUNG RADS 4 (very high risk) lesions, 30 lung cancers (2.5%), including 18 at stage I-III treated with curative intent (60%); >50% had intercurrent cardiovascular disease and COPD seen on LDCT. We have additionally screened 574 cases, including 51 Native Americans (in a structured assessment of one tribe). Of the Native Americans, 5 had LUNG RADS 3-4 (high risk) lesions, but no cancers have been identified to date. For the total series of 1774 subjects with age-related negative case selection bias, 42 lung cancers have been identified (2.4%), 26 of which were treated with curative intent (62%) via surgery, radiation, or chemo-radiation. Only one patient of 18 treated with curative intent in the first series of 30 lung cancers has relapsed to date (median follow up 3 years, with 5 without evidence of disease beyond 3.5 years). These data confirm a shift to detection of early-stage lung cancer in this large under-served population, with an apparent potential for cure. Conclusion: Mobile LDCT yields a higher screening rate for under-served patients than prior hallmark trials, with a consequent shift to early-stage detection of lung cancer, with sustained treatment-induced complete remissions beyond 4 years. This approach could be applied to improve national lung cancer survival in the under-served. Citation Format: Derek Raghavan, Darcy Doege, Mellisa Wheeler, Kia Dungan, John Doty III, Glenn Hickman, Kathryn Mileham, Daniel Carrizosa. Screening under-served populations by mobile low dose computerized tomography (LDCT) scans results in stage shift with potential cures: Time for a change in health policy? [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr PR006.

Smoking Cessation Management for Lung Cancer Smokers: An Essential Component of Treatment

In 2020 lung cancer has been the leading cause of cancer death, with an estimated 1.8 million deaths; in other words of 18% of cancer deaths. Tobacco smoking is cause of 90% of lung cancers. Despite advances in lung cancer treatment, tobacco control is the most effective measure for curbing the lung cancer epidemic. Smoking cessation, at all stages of the cancer process, is associated with benefits in terms of cure, increased life expectancy and quality of life for patients, reduced medical and surgical complications, as well as it reduces risks of recurrence or of a second primary cancer. Smoking cessation medications combined with psychological support facilitate to quit smoking. Smoking cessation management is an essential component of lung cancer treatment. Researches into the best modalities to manage smoking cessation in lung cancer patients must be conducted. Nevertheless, healthcare professionals involved in the care of cancer patients must be trained to provide personalized assistance to help smokers stopping smoking.

Lung Cancer in Non-Smokers: Clinicopathological and Survival Differences from Smokers.

Background Lung cancer in non-smokers is a clinically distinct entity based on unique epidemiology, clinicopathology, genetics, treatment response, and outcome. Data from Indian centres are scarce. The objective of this study was to compare the frequency, clinical characteristics, driver mutations, and survival of non-smoking and smoking lung cancer patients treated at a tertiary cancer centre in North India. Methodology Two years of data on 724 consecutive lung cancer patients were assessed. Clinical, demographics, smoking history, and EGFR and ALK mutation test results were collected. Descriptive and inferential statistics were applied. Survival analysis was performed using the Kaplan-Meier method. Results Non-smokers comprised 40.9% of the study sample. Non-smokers were more likely than smokers to experience disease onset at a younger age (P = 0.004) and metastasis (P < 0.001).The tumor histology showed significant differences (P < 0.001), with non-smokers more likely to be diagnosed with adenocarcinoma (77.4%), while squamous and small cell histologies were commonly found among smokers (37.6% and 13.8%, respectively). The EGFR mutation and ALK rearrangement rates in the cohort were 23.3% and 10.1%, respectively, and were more frequent in non-smoking patients. Overall, 10-year survival was 7%, with a significantly better survival rate of non-smokers than smokers (median survival time of 15.13 vs10.17 months; P = 0.012). Conclusions About four out of 10 patients diagnosed with lung cancer at our centre were non-smokers. They were more often young, diagnosed at an advanced stage, with predominantly adenocarcinoma histology, and had a threefold higher frequency of EGFR mutations than smokers. In our cohort, non-smokers appear to be a targetable group with better survival than smokers.

The combination of chronic stress and smoke exacerbated depression-like changes and lung cancer factor expression in A/J mice: Involve inflammation and BDNF dysfunction.

Depression is positively correlated with the high incidence and low survival rate of cancers, while more cancer patients suffer depression. However, the interaction between depression and cancer, and possible underline mechanisms are unclear. Chronic unpredictable mild stress (CUMS) was used to induce depression, and smoke to induce lung cancer in lung cancer vulnerable AJ mice. After 8 weeks, sucrose preference and forced swimming behaviors were tested. Blood corticosterone concentration, and levels of cytokines, lung cancer-related factors, brain-derived neurotrophic factor (BDNF) and apoptosis-related factors in the lung, amygdala and hippocampus were measured. Compared to control group, CUMS or smoke decreased sucrose consumption and increased immobility time, which were deteriorated by stress+smoke. CUMS, smoke or both combination decreased mononuclear viability and lung TNF-α concentration, increased serum corticosterone and lung interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10, IL-12 and HSP-90α concentrations. Furthermore, stress+smoke caused more increase in corticosterone and IL-10, but decreased TNF-α. In parallel, in the lung, Bcl-2/Bax and lung cancer-related factors CDK1, CDC20, P38α etc were significantly increased in stress+smoke group. Moreover, CUMS decreased BDNF, while CUMS or smoke increased TrkB and P75 concentrations, which were exacerbated by stress+smoke. In the amygdala, except for CUMS largely increased Bax/Bcl-2 and decreased TrkB, each single factor decreased BDNF and IL-10, but increased P75, IL-1β, IL-12, TNF-α concentrations. Changes in Bax/Bcl-2, IL-10 and TNF-α were further aggravated by the combination. In the hippocampus, except for CUMS largely increased P75 concentration, each single factor significantly increased Bax/Bcl-2 ratio, IL-1β and TNF-α, but decreased BDNF, TrkB and IL-10 concentrations. Changes in Bax, Bax/Bcl-2, IL-10 and TNF-α were further aggravated by the combination. These results suggest that a synergy between CUMS and smoke exposure could promote the development of depression and lung cancer, through CUMS increased the risk of cancer occurrence, and conversely lung cancer inducer smoke exposure deteriorated depressive symptoms.

Geographic Patterns in U.S. Lung Cancer Mortality and Cigarette Smoking.

Despite the success of smoking cessation campaigns, lung cancer remains the leading cause of cancer death in the U.S. Variations in smoking behavior and lung cancer mortality are evident by sex and region. Applying geospatial methods to lung cancer mortality data from the National Vital Statistics System and county-level estimates of smoking prevalences from the NCI's Small Area Estimates of Cancer-Related Measures, we evaluated patterns in lung cancer mortality rates (2005-2018) in relation to patterns in ever cigarette smoking prevalences (1997-2003). Overall, ever smoking spatial patterns were generally associated with lung cancer mortality rates, which were elevated in the Appalachian region and lower in the West for both sexes. However, we also observed geographic variation in mortality rates that is not explained by smoking. Using Lee's L statistic for assessing bivariate spatial association, we identified counties where the ever smoking prevalence was low and lung cancer rates were high. We observed a significant cluster of counties (n = 25; P values ranging from 0.001 to 0.04) with low ever smoking prevalence and high mortality rates among females around the Mississippi River region south of St. Louis, Missouri and a similar and smaller cluster among males in Western Mississippi (n = 12; P values ranging from 0.002 to 0.03) that has not been previously described. Our analyses identified U.S. counties where factors other than smoking may be driving lung cancer mortality. These novel findings highlight areas where investigation of environmental and other risk factors for lung cancer is needed.

Identification of Formaldehyde-Induced DNA-RNA Cross-Links in the A/J Mouse Lung Tumorigenesis Model.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen present in tobacco products, and exposure to it is likely one of the factors contributing to the development of lung cancer in cigarette smokers. To exert its carcinogenic effects, NNK must be metabolically activated into highly reactive species generating a wide spectrum of DNA damage. We have identified a new class of DNA adducts, DNA-RNA cross-links found for the first time in NNK-treated mice lung DNA using our improved high-resolution accurate mass segmented full scan data-dependent neutral loss MS3 screening strategy. The levels of these DNA-RNA cross-links were found to be significantly higher in NNK-treated mice compared to the corresponding controls, which is consistent with higher levels of formaldehyde due to NNK metabolism as compared to endogenous levels. We hypothesize that this DNA-RNA cross-linking occurs through reaction with NNK-generated formaldehyde and speculate that this phenomenon has broad implications for NNK-induced carcinogenesis. The structures of these cross-links were characterized using high-resolution LC-MS2 and LC-MS3 accurate mass spectral analysis and comparison to a newly synthesized standard. Taken together, our data demonstrate a previously unknown link between DNA-RNA cross-link adducts and NNK and provide a unique opportunity to further investigate how these novel NNK-derived DNA-RNA cross-links contribute to carcinogenesis in the future.

307P Differential expression profiling of transcripts in stage IIIA non-small cell lung cancer (NSCLC) of smokers and non-smokers cases of north India: A geneto-environmental study

Several epidemiological and experimental studies suggest that the etiology of many chronic illnesses is caused by the joint effect between genetics and the environment. Smoking tobacco is the major hazard feature for lung cancer in Indian subcontinent especially men, compare to woman where, other important risk factors i.e., exposure to agents and level of pollutions are responsible. So, the aim of the study is to compare the expression level of transcript-based biomarkers IDH1, CEA, Cyfra21-1, and TPA in NSCLC fifty tumor tissue stage IIIa patients compared to control benign tissues of smokers and non-smokers cases living in areas with air quality categorized as poor (AQI 201–300) or moderate (AQI 101–200).

An Overview of Radon Concentration in Southwestern Nigeria

Without a doubt, radon is a harmful gas that is the greatest cause of lung cancer in nonsmokers and the second biggest cause of lung cancer in smokers. However, due to a lack of knowledge and limited research, this poisonous gas has received little attention in the southwestern area of Nigeria. As a result, a few studies have been compiled with the goal of policymakers using it as a baseline for radon monitoring in the region, which may also be used as a reference for future studies.

126P Clonal architecture and genomic features of smoking versus non-smoking oncogene-driven East-Asian non-small cell lung cancer

Unlike smoking-related lung cancers, oncogene-driven non-small cell lung cancers (NSCLC) are characterized by low mutational burden and complex genomic landscapes. In East Asia, ∼30% of patients with EGFR-driven NSCLC have a history of smoking. This study aims to investigate the impact of tobacco exposure on clonal architecture of EGFR-mutant NSCLC.

The Effect of Smoking on the Morphology of Lung Cancer

Smoking as a cause of cancer development has been the subject of research by the International Agency for Research on Cancer (IARC) [1, 2]. The highest rates are for lung (up to 90% of cases), oral cavity (92%) and larynx (87%) cases [3]. Smoking is one of the most important causes in the etiology of lung cancer [3, 4]. The purpose of the study was to determine whether smoking had an effect on the morphological type of lung cancer. One hundred and fifty patients with histologically proven lung cancer by gender, age, smoking experience, and morphology of lung cancer were studied. The number of men is twice that of women; the highest number of patients is between 40 and 60 years of age. 76.6% of patients are active smokers, 88.6% of them have used cigarettes for more than 10 years, and 59% have smoked more than 20 cigarettes daily. Of the nonsmoking patients, 48.6% are passive smokers. The distribution by morphological type of lung cancer in smokers indicates that the ratio of squamous type of cancer (59%) is the highest, followed by adenocarcinoma (29.5%), and small cellular cancer (11.3%).

Lung Cancer in the Non-smoker: A Patient View Focused on the Hopes and Challenges Facing the Non-smoker Population

A patient view paper focused on hopes and challenges facing the never smoker lung cancer population – from lived experience, unexpected diagnosis, treatment and subsequent immersion in lung cancer research and patient advocacy over many years, citing examples, references and events organised to explore the subject by UK research institutions. Material/methodsBased on lived experience, invited patient perspective conference presentations including National Cancer Research Institute (NCRI) never smoker lung cancer research strategy event opening presentation and subsequent article, includes references to relevant papers/findings and points raised during research events/group discussions, alongside personal experiences and beliefs. ResultsDiscussions with clinicians, events, surveys, meetings and virtual discussions all revealed a dearth of evidence available to identify the best way to deal with this patient cohort at almost every aspect of their experience – from missed/late diagnosis, to screening potential (non-existent), mutation driven treatments (what about those ineligible?), and psychosocial/psychological aspects given their different life stage from older traditional lung cancer patients. ConclusionMore effort and focus are needed to better understand what is driving these cases, how best to detect them sooner and respond/refer to treatments as well as developing screening methods alongside increased public and healthcare professional awareness raising and tools to support clinicians in earlier detection.

Relationship between Trace Elements Levels and Lung Cancer Patients in Southern Iraq

Background: Our life relies on our ability to use all sorts of materials, like trace elements, in the world for our needs. The using of heavy metals has greatly contributed to the comfort of our everyday lives. Blood is directly affected by poisoning when such metals are inhaled from environments where heavy metals occur in high levels. Research is constantly advancing our knowledge of the connection between various trace elements and disease, particularly cancer, since the effects of heavy metals on human health remain a serious health concern.&#x0D; Objective: The objective of this work is to establish levels of a range of elements in human blood, serum and hair samples of patient undergo lung cancer comparing with control (healthy persons) so that potential exposures can be better identified in future cases.&#x0D; Methods: Elements concentrations including As(arsenic), Ba(barium), Co(cobalt), Li(lithium), Mg(magnesium), Mn(manganese), Mo(molybdenum), Rb(rubidium), Sr(strontium) and Ti(titanium) was analysis used MS ICP (an inductively coupled plasma atomic absorption spectrophotometer).&#x0D; Results: Test found that Mn has substantially (p&lt;0.05) high concentration in three tissues including whole blood, serum, and hair of patients with lung cancer (291,487.2,68.03) ug / l respectively. In comparison as occurs in the lowest concentration. Sr was 77.5ug / l, Rb 41.6ug / l, and Ba 35.2ug / g. On other hand, Co, Li, Mg, Mo and Ti were found in low levels ranged 1.7-5.5 ug/l, in whole blood of patients. Hair samples accumulated the lowest concentration of As, Ba, Co, Mg, Mn and Rb. When we compare the concentration of trace elements between lung patients and control samples, that clear most of the elements accumulate at high levels in lung cancer patients. Result found significantly high As, Ba, Co, Mg, Mo concentration in whole blood and serum of lung cancer patients, in contract, Li, Mn and Rb occur in high levels in whole blood of control sample. Even as hair of control samples have elevated levels of As, Sr and Ti. However, concentrations of trace elements in the whole blood of smokers and non-smokers showed that all ten elements accumulated at elevated levels in the blood of smokers relative to non-smokers. Spearman correlation found significantly positive correlation among trace elements in the blood of patients with smoker lung cancer and non-smokers.&#x0D; Conclusion: The study conclude that trace metals level in smokers persons are elevated than non-smokers. The findings of this study lend some support to the link between heavy metals pollution and lung cancer cases.

Stage Shift Improves Lung Cancer Survival: Real-World Evidence

IntroductionLung cancer is the global leading cause of cancer death. Taiwan initiated several health policies including smoking cessation, precision therapy, and low-dose computed tomography (LDCT) screening in 1997. We aimed to investigate the effect of public policies on lung cancer survival. MethodsWe retrieved the nationwide cancer registry from the Ministry of Health and Welfare to evaluate the smoking prevalence and lung cancer incidence and mortality from 1994 to 2020. We also conducted a retrospective analysis of clinical characteristics and survival on 17,298 patients with lung cancer from 2006 to 2019 using the National Taiwan University Hospital database. ResultsTaiwan initiated an anti-smoking campaign in 1997, reimbursed tyrosine kinase inhibitors since 2004, and conducted an LDCT screening trial in 2015. Lung cancer incidence keeps rising but the annual percent change in mortality rate gradually decreased from 0.41% to −2.41%. The National Taiwan University Hospital data revealed that the 5-year survival substantially improved from 22.1% in 2006 to 2011 to 54.9% in 2015 to 2020. Improvement was observed in all stages, especially late stages (stage III: from 17.2% to 35.2%; stage IV: from 7.9% to 16.5%). Furthermore, a remarkable shift in cancer stage was observed (stage 0, I, and IIincreased from 19.3% to 62.8%, and stage III and IV decreased from 70.9% to 33.8%). The prominent improvement in survival was primarily driven by the stage shift from advanced to localized, potentially curable disease. ConclusionsThis real-world evidence suggested an association between improved survival and LDCT screening and the diagnostic shift from late to early-stage of lung cancer, highlighting the importance of early detection for lung cancer control.

1075P Tobacco smoking related mutational signatures (MS) in classifying smoking and non-smoking associated metastatic non-small cell lung cancer (mNSCLC)

Patient-reported smoking history is frequently used as stratification factor or for subgroup analyses in NSCLC directed clinical research, even though this classification does not fully reflect the mutational processes in a tumour. Additionally, the label ‘smoker’ can add to the lung cancer stigma. Next generation sequencing can be used to identify MS associated with tobacco smoking, such as the single base MS (SBS) 4 and indel based MS (ID) 3. This provides an opportunity to redefine the classification of smoking and non-smoking associated NSCLC based on individual genomic tumour characteristics.

Transcription Factor MAFB as a Prognostic Biomarker for the Lung Adenocarcinoma.

MAFB is a basic leucine zipper (bZIP) transcription factor specifically expressed in macrophages. We have previously identified MAFB as a candidate marker for tumor-associated macrophages (TAMs) in human and mouse models. Here, we analyzed single-cell sequencing data of patients with lung adenocarcinoma obtained from the GEO database (GSE131907). Analyzed data showed that general macrophage marker CD68 and macrophage scavenger receptor 1 (CD204) were expressed in TAM and lung tissue macrophage clusters, while transcription factor MAFB was expressed specifically in TAM clusters. Clinical records of 120 patients with lung adenocarcinoma stage I (n = 57), II (n = 21), and III (n = 42) were retrieved from Tsukuba Human Tissue Biobank Center (THB) in the University of Tsukuba Hospital, Japan. Tumor tissues from these patients were extracted and stained with anti-human MAFB antibody, and then MAFB-positive cells relative to the tissue area (MAFB+ cells/tissue area) were morphometrically quantified. Our results indicated that higher numbers of MAFB+ cells significantly correlated to increased local lymph node metastasis (nodal involvement), high recurrence rate, poor pathological stage, increased lymphatic permeation, higher vascular invasion, and pleural infiltration. Moreover, increased amounts of MAFB+ cells were related to poor overall survival and disease-free survival, especially in smokers. These data indicate that MAFB may be a suitable prognostic biomarker for smoker lung cancer patients.

Quantitation of DNA Adducts Resulting from Acrolein Exposure and Lipid Peroxidation in Oral Cells of Cigarette Smokers from Three Racial/Ethnic Groups with Differing Risks for Lung Cancer.

The Multiethnic Cohort Study has demonstrated that the risk for lung cancer in cigarette smokers among three ethnic groups is highest in Native Hawaiians, intermediate in Whites, and lowest in Japanese Americans. We hypothesized that differences in levels of DNA adducts in oral cells of cigarette smokers would be related to these differing risks of lung cancer. Therefore, we used liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry to quantify the acrolein-DNA adduct (8R/S)-3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10(3H)-one (γ-OH-Acr-dGuo, 1) and the lipid peroxidation-related DNA adduct 1,N6-etheno-dAdo (εdAdo, 2) in DNA obtained by oral rinse from 101 Native Hawaiians, 101 Whites, and 79 Japanese Americans. Levels of urinary biomarkers of nicotine, acrolein, acrylonitrile, and a mixture of crotonaldehyde, methyl vinyl ketone, and methacrolein were also quantified. Whites had significantly higher levels of γ-OH-Acr-dGuo than Japanese Americans and Native Hawaiians after adjusting for age and sex. There was no significant difference in levels of this DNA adduct between Japanese Americans and Native Hawaiians, which is not consistent with the high lung cancer risk of Native Hawaiians. Levels of εdAdo were modestly higher in Whites and Native Hawaiians than in Japanese Americans. The lower level of DNA adducts in the oral cells of Japanese American cigarette smokers than Whites is consistent with their lower risk for lung cancer. The higher levels of εdAdo, but not γ-OH-Acr-dGuo, in Native Hawaiian versus Japanese American cigarette smokers suggest that lipid peroxidation and related processes may be involved in their high risk for lung cancer, but further studies are required.

Early natural menopause is associated with poor lung health and increased mortality among female smokers

Early natural menopause has been regarded as a biomarker of reproductive and somatic aging. Cigarette smoking is the most harmful factor for lung health and also an established risk factor for early menopause. Understanding the effect of early menopause on health outcomes in middle-aged and older female smokers is important to develop preventive strategies. This study aimed to examine the associations of early menopause with multiple lung health and aging biomarkers, lung cancer risk, and all-cause and cause-specific mortality in postmenopausal women who were moderate or heavy smokers. This study was conducted on postmenopausal women with natural (n=1038) or surgical (n=628) menopause from the Pittsburgh Lung Screening Study. The Pittsburgh Lung Screening Study is a community-based research cohort of current and former smokers, screened with low-dose computed tomography and followed up for lung cancer. Early menopause was defined as occurring before 45 years of age. The analyses were stratified by menopause types because of the different biological and medical causes of natural and surgical menopause. Statistical methods included linear model, generalized linear model, linear mixed-effects model, and time-to-event analysis. The average age of the 1666 female smokers was 59.4±6.7 years, with 1519 (91.2%) of the population as non-Hispanic Whites and 1064 (63.9%) of the population as current smokers at baseline. Overall, 646 (39%) women reported early menopause, including 198 (19.1%) women with natural menopause and 448 (71.3%) women with surgical menopause (P<.001). Demographic variables did not differ between early and nonearly menopause groups, regardless of menopause type. Significant associations were identified between early natural menopause and higher risk of wheezing (odds ratio, 1.65; P<.01), chronic bronchitis (odds ratio, 1.73; P<.01), and radiographic emphysema (odds ratio, 1.70; P<.001) and lower baseline lung spirometry in an obstructive pattern (-104.8 mL/s for forced expiratory volume in the first second with P<.01,-78.6 mL for forced vital capacity with P=.04, and-2.1% for forced expiratory volume in the first second-to-forced vital capacity ratio with P=.01). In addition, early natural menopause was associated with a more rapid decline of forced expiratory volume in the first second-to-forced vital capacity ratio (-0.16% per year; P=.01) and incident airway obstruction (odds ratio, 2.02; P=.04). Furthermore, women early natural menopause had a 40% increased risk of death (P=.023), which was mainly driven by respiratory diseases (hazard ratio, 2.32; P<.001). Mediation analyses further identified that more than 33.3% of the magnitude of the associations between early natural menopause and all-cause and respiratory mortality were explained by baseline forced expiratory volume in the first second. Additional analyses in women with natural menopause identified that the associations between continuous smoking and subsequent lung cancer risk and cancer mortality were moderated by early menopause status, and females with early natural menopause who continued smoking had the worst outcomes (hazard ratio, >4.6; P<.001). This study did not find associations reported above in female smokers with surgical menopause. Early natural menopause was found to be a risk factor for malignant and nonmalignant lung diseases and mortality in middle-aged and older female smokers. These findings have strong public health relevance as preventive strategies, including smoking cessation and chest computed tomography screening, should target this population (ie, female smokers with early natural menopause) to improve their postmenopausal health and well-being.

Assessment of Lung Cancer Risk Among Smokers for Whom Annual Screening Is Not Recommended

The US Preventive Services Task Force does not recommend annual lung cancer screening with low-dose computed tomography (LDCT) for adults aged 50 to 80 years who are former smokers with 20 or more pack-years of smoking who quit 15 or more years ago or current smokers with less than 20 pack-years of smoking. To determine the risk of lung cancer in older smokers for whom LDCT screening is not recommended. This cohort study used the Cardiovascular Health Study (CHS) data sets obtained from the National Heart, Lung and Blood Institute, which also sponsored the study. The CHS enrolled 5888 community-dwelling individuals aged 65 years and older in the US from June 1989 to June 1993 and collected extensive baseline data on smoking history. The current analysis was restricted to 4279 individuals free of cancer who had baseline data on pack-year smoking history and duration of smoking cessation. The current analysis was conducted from January 7, 2022, to May 25, 2022. Current and prior tobacco use. Incident lung cancer during a median (IQR) of 13.3 (7.9-18.8) years of follow-up (range, 0 to 22.6) through December 31, 2011. A Fine-Gray subdistribution hazard model was used to estimate incidence of lung cancer in the presence of competing risk of death. Cox cause-specific hazard regression models were used to estimate hazard ratios (HRs) and 95% CIs for incident lung cancer. There were 4279 CHS participants (mean [SD] age, 72.8 [5.6] years; 2450 [57.3%] women; 663 [15.5%] African American, 3585 [83.8%] White, and 31 [0.7%] of other race or ethnicity) included in the current analysis. Among the 861 nonheavy smokers (<20 pack-years), the median (IQR) pack-year smoking history was 7.6 (3.3-13.5) pack-years for the 615 former smokers with 15 or more years of smoking cessation, 10.0 (5.3-14.9) pack-years for the 146 former smokers with less than 15 years of smoking cessation, and 11.4 (7.3-14.4) pack-years for the 100 current smokers. Among the 1445 heavy smokers (20 or more pack-years), the median (IQR) pack-year smoking history was 34.8 (26.3-48.0) pack-years for the 516 former smokers with 15 or more years of smoking cessation, 48.0 (35.0-70.0) pack-years for the 497 former smokers with less than 15 years of smoking cessation, and 48.8 (31.6-57.0) pack-years for the 432 current smokers. Incident lung cancer occurred in 10 of 1973 never smokers (0.5%), 5 of 100 current smokers with less than 20 pack-years of smoking (5.0%), and 26 of 516 former smokers with 20 or more pack-years of smoking with 15 or more years of smoking cessation (5.0%). Compared with never smokers, cause-specific HRs for incident lung cancer in the 2 groups for whom LDCT is not recommended were 10.54 (95% CI, 3.60-30.83) for the current nonheavy smokers and 11.19 (95% CI, 5.40-23.21) for the former smokers with 15 or more years of smoking cessation; age, sex, and race-adjusted HRs were 10.06 (95% CI, 3.41-29.70) for the current nonheavy smokers and 10.22 (4.86-21.50) for the former smokers with 15 or more years of smoking cessation compared with never smokers. The findings of this cohort study suggest that there is a high risk of lung cancer among smokers for whom LDCT screening is not recommended, suggesting that prediction models are needed to identify high-risk subsets of these smokers for screening.

The 1964 US Surgeon General's report on smoking and health.

The 1964 report of the US Surgeon General on smoking and health made an authoritative case that tobacco smoking was a cause of premature deaths from lung cancer and chronic bronchitis. It justified the practice of drawing causal inferences from epidemiological studies, specified influential criteria for doing so, and made use of an early form of meta-analysis.

Association of CYP2A6 Genetic Polymorphism and Lung Cancer in Female Never Smokers

Background: The major significant factor that affected lung cancer development among female passive smokers is environmental tobacco smoke. Nicotine can be found in a never smoker population, such as a child whose father is a smoker. Lung carcinogenesis in never smoker populations is affected by nicotine metabolism by CYP2A6 gene, which encodes the main nicotine metabolizing-enzyme. The aim of this study was to assess the genetic polymorphism of CYP2A6 and its association with secondhand smokers among females who have suffered from lung cancer in North Sumatra population.Materials and methods: This study was a case-control study, composed of 53 case subjects and 46 control subjects that were involved through a purposive sampling technique from two hospitals in Medan. PCR-RFLP was used for the examination of CYP2A6 gene to determine the genotype. The data were analyzed with conditional logistic regression test using Epi Info 7.0 software.Results: The most common genotype of CYP2A6 detected in this study was *1B/*1B (40.4%), while *1B allele had the highest prevalence (55.5%). There was no significant association between CYP2A6 genotype (p-value=0.61) or alleles (p-value=0.25) and the incidence of lung cancer.Conclusion: There was no association between CYP2A6 polymorphism and the incidence of lung cancer in secondhand smoker females.Keywords: CYP2A6, PCR-RFLP, female secondhand smokers, lung cancer