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Purpose: In 2021, the United States Preventive Services Task Force (USPSTF) revised their 2013 recommendations for lung cancer screening eligibility by lowering the pack-year history from 30+ to 20+ pack-years and the recommended age from 55 to 50 years. Simulation studies suggest that Black persons and females will benefit most from these changes, but it is unclear how the revised USPSTF recommendations will impact geographic, health-related, and other sociodemographic characteristics of those eligible., Methods: This cross-sectional study employed data from the 2017-2020 Behavioral Risk Factor Surveillance System surveys from 23 states to compare age, gender, race, marital, sexual orientation, education, employment, comorbidity, vaccination, region, and rurality characteristics of the eligible population according to the original 2013 USPSTF recommendations with the revised 2021 USPSTF recommendations using chi-squared tests. This study compared those originally eligible to those newly eligible using the BRFSS raking-dervived weighting variable., Results: There were 30,190 study participants. The results of this study found that eligibility increased by 62.4% due to the revised recommendations. We found that the recommendation changes increased the proportion of eligible females (50.1% vs 44.1%), Black persons (9.2% vs 6.6%), Hispanic persons (4.4% vs 2.7%), persons aged 55-64 (55.8% vs 52.6%), urban-dwellers(88.3% vs 85.9%), unmarried (3.4% vs 2.5%) and never married (10.4% vs 6.6%) persons, as well as non-retirees (76.5% vs 56.1%) Respondents without comorbidities and COPD also increased., Conclusion: It is estimated that the revision of the lung cancer screening recommendations decreased eligibility disparities in sex, race, ethnicity, marital status, respiratory comorbidities, and vaccination status. Research will be necessary to estimate whether uptake patterns subsequently follow the expanded eligibility patterns., (© 2024. The Author(s).)

The question of whether cigarette smoking was associated with lung cancer was central to the expansion of epidemiology into the study of chronic diseases in the 1950s. The culmination of this era was the 1964 report of the Advisory Committee to the Surgeon General, a landmark document that included an objective synthesis of the evidence of the health consequences of smoking according to causal criteria. The report concluded that cigarette smoking was a cause of lung cancer in men and sufficient in scope that "remedial action" was warranted at the societal level. The 2014 Surgeon General's report commemorates the 50th anniversary of the 1964 report. The evidence on the health consequences of smoking has been updated many times in Surgeon General's reports since 1964. These have summarized our increasingly greater understanding of the broad spectrum of the deleterious health effects of exposure to tobacco smoke across most major organ systems. In turn, this evidence has been translated into tobacco control strategies implemented to protect the public's health. The Surgeon General report process is an enduring example of evidence-based public health in practice. Substantial progress has been made, but cigarette smoking remains one of the most pressing global health issues of our time.

Background: Sphingosine-1-phosphate (S1P) and ceramides are bioactive signaling sphingolipids that regulate pathways that are central to cancer pathogenesis., Methods: A nested case-control study was implemented to test whether prediagnostic circulating concentrations of S1P and ceramides were associated with future lung cancer risk. In the community-based CLUE II cohort study in Washington County, Maryland, the study consisted of 100 incident lung cancer cases, each matched to two cancer-free controls on age, sex, race, and cigarette smoking status. Plasma stored at -70°C at the beginning of follow-up in 1989 was assayed for sphingolipids using liquid chromatography/tandem mass spectrometry methodology (LC/MS-MS)., Results: Compared with controls, geometric mean plasma concentrations of S1P and total ceramides were 2.9% (P = 0.10) and 5.1% (P = 0.02), respectively, greater in lung cancer cases. For S1P, the ORs and 95% confidence intervals (CI) for lung cancer risk were 2.7 (1.2-5.9), 2.7 (1.1-6.4), and 1.9 (0.8-4.5) for the second, third, and highest fourth, respectively, compared with the lowest fourth (overall P = 0.006). Compared with those with total ceramide concentrations in the lowest fourth, the ORs (and 95% CI) for lung cancer risk were 1.6 (0.7-3.3), 1.5 (0.7-3.4), and 2.1 (0.9-4.7) for the second, third, and highest fourth, respectively (P(trend) = 0.01)., Conclusions: Higher concentrations of S1P and total ceramide in plasma were associated with increased future risk of lung cancer., Impact: These novel findings suggest that perturbation of sphingolipid metabolism and S1P generation may either contribute to the etiology of lung cancer or be a marker of latent lung cancer., (©2013 AACR)

Background: Ever since a lung cancer epidemic emerged in the mid-1900 s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research., Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk., Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application., Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers.

Lung cancer is the leading cause of cancer death among women in the United States and other Western nations. The predominant cause of lung cancer in women is active cigarette smoking. Secondhand exposure to tobacco smoke is another important cause. The hypothesis that women are more susceptible than men to smoking-induced lung cancer has not been supported by the preponderance of current data, as noted by De Matteis et al. (Am J Epidemiol. 2013;177(7):601-612) in the accompanying article. However, aspects of lung cancer in men and women continue to indicate potential male-female differences in the etiology of lung cancer, based on several observations: 1) among never smokers, women have higher lung cancer incidence rates than men; 2) there is evidence that estrogen may contribute to lung cancer risk and progression; and 3) there are different clinical characteristics of lung cancer in women compared with men, such as the higher percentage of adenocarcinomas in never smokers, the greater prevalence of epidermal growth factor receptor gene (EGFR) mutations in adenocarcinomas among never smokers, and better prognosis. Considered in total, observations such as these offer enticing clues that, even amid cigarette smoking and other commonalities in the etiology of lung cancer in men and women, distinct differences may remain to be delineated that could potentially be of scientific and clinical relevance.

Background: The primary risk factor for chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) is cigarette smoking but shared susceptibility factors, such as variations in the matrix metalloproteinase-1 (MMP1) gene, may also underlie both diseases., Materials and Methods: Cases with prevalent COPD (n=167), incident NSCLC (n=242), or prevalent COPD plus incident NSCLC (n=128) were compared to disease-free controls (n=338) to assess six MMP1 polymorphisms. The association between these polymorphisms and survival in NSCLC was also evaluated., Results: Rs11292517 among African-Americans [odds ratio (OR)=5.48, 95% confidence interval (CI)=1.17-25.72] and rs2071230 among Caucasians (OR=2.51, 95% CI=1.09-5.77) appeared to be associated with NSCLC risk in the presence of COPD. Rs470558 appeared to be associated with survival in NSCLC among African-Americans (hazard ratio=3.94; 95%CI=1.14-13.63). No associations remained after adjusting for multiple comparisons., Conclusion: Polymorphisms in MMP1 were not consistently associated with prevalent COPD or incident NSCLC nor with survival in NSCLC.

Background: Through their roles in tissue remodeling, variants in the genes that encode alpha1-antitrypsin (AAT) and neutrophil elastase (NE) were hypothesized to be associated with the risk of both chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC)., Materials and Methods: Cases with prevalent COPD (n=145), incident NSCLC (n=203) or prevalent COPD plus NSCLC (n=118) were compared to disease-free controls (n=317), to assess two functional polymorphisms in serpin peptidase inhibitor, clade A, member 1 (SERPINA1), which encodes AAT, and eleven tagging polymorphisms in and around elastase 2 (ELA2), which encodes NE. All analyses were stratified by race., Results: Among African-Americans, the less efficient SERPINA1 variant appeared to be associated with increased risk of prevalent COPD but only in the presence of NSCLC (odds ratio=7.39; 95% confidence interval=1.03-53.21) and not after correcting for multiple comparisons., Conclusion: Variations in SERPINA1 and ELA2 were not consistently or strongly associated with the risk of either COPD or NSCLC in either race.

Background: Due predominantly to cigarette smoking, lung cancer is the leading cancer-related cause of death worldwide. Cruciferous vegetables may reduce lung cancer risk. The association between intake of cruciferous vegetables and lung cancer risk was investigated in the CLUE II study, a community-based cohort established in 1989., Methods: We matched 274 incident cases of lung cancer diagnosed from 1990 to 2005 to 1,089 cancer-free controls on age, sex, and cigarette smoking. Dietary information was collected at baseline. Multivariable odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression., Results: Intake of cruciferous vegetables was inversely associated with lung cancer risk (highest-versus-lowest fourth: OR (Q4vsQ1), 0. 57; 95% CI, 0.38-0.85; P-trend = 0.01). The inverse associations held true for former smokers (OR(Q4vsQ1), 0.49; 95% CI, 0.27-0.92; P-trend = 0.05) and current smokers (OR(Q4vsQ1), 0.52; 95% CI, 0.29-0.95; P-trend = 0.02)., Conclusions: After carefully controlling for cigarette smoking, higher intake of cruciferous vegetable was associated with lower risk of lung cancer., Impact: The observed inverse association coupled with accumulating evidence suggests that intake of cruciferous vegetables is inversely associated with lung cancer risk, and this association seems to hold true beyond the confounding effects of cigarette smoking., (©2010 AACR.)

Background: Exposure to secondhand smoke during adulthood has detrimental health effects, including increased lung cancer risk. Compared with adults, children may be more susceptible to secondhand smoke. This susceptibility may be exacerbated by alterations in inherited genetic variants of innate immunity genes. We hypothesized a positive association between childhood secondhand smoke exposure and lung cancer risk that would be modified by genetic polymorphisms in the mannose binding lectin-2 (MBL2) gene resulting in well-known functional changes in innate immunity., Methods: Childhood secondhand smoke exposure and lung cancer risk was assessed among men and women in the ongoing National Cancer Institute-Maryland Lung Cancer (NCI-MD) study, which included 624 cases and 348 controls. Secondhand smoke history was collected via in-person interviews. DNA was used for genotyping the MBL2 gene. To replicate, we used an independent case-control study from Mayo Clinic consisting of 461 never smokers, made up of 172 cases and 289 controls. All statistical tests were two-sided., Results: In the NCI-MD study, secondhand smoke exposure during childhood was associated with increased lung cancer risk among never smokers [odds ratio (OR), 2.25; 95% confidence interval (95% CI), 1.04-4.90]. This was confirmed in the Mayo study (OR, 1.47; 95% CI, 1.00-2.15). A functional MBL2 haplotype associated with high circulating levels of MBL and increased MBL2 activity was associated with increased lung cancer risk among those exposed to childhood secondhand smoke in both the NCI-MD and Mayo studies (OR, 2.52; 95% CI, 1.13-5.60, and OR, 2.78; 95% CI, 1.18-3.85, respectively)., Conclusions: Secondhand smoke exposure during childhood is associated with increased lung cancer risk among never smokers, particularly among those possessing a haplotype corresponding to a known overactive complement pathway of the innate immune system.

Purpose: Previous studies did not discriminate wild-type from hemizygous genotypes of GSTM1 and GSTT1. In this study, we investigated wild-type, hemizygous deletion, and homozygous deletion genotypes of GSTM1 and GSTT1 and lung cancer risk., Methods: We conducted a nested case-control study of 143 primary incident lung cancer cases matched to 447 cancer-free controls. Genotyping was carried out using a real-time polymerase chain reaction (PCR)-based assay. Conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI)., Results: Compared to GSTM1 wild-type carriers, the relative odds of lung cancer increased from 1.49 (95% CI=0.66-3.40) to 1.80 (95% CI=0.81-4.02) for the hemizygous and homozygous deletion genotypes, respectively (p-trend=0.13). The strongest associations were seen among those who smoked less than one pack per day and had greater than or equal to one deletion variant of GSTM1 (OR=3.25; 95% CI=0.93-11.34; p-trend=0.07) whereas the reverse was observed for smokers who smoked greater than or equal to one pack per day (OR=0.80; 95% CI=0.24-2.67; p-interaction=0.08). No clear associations were observed for GSTT1 genotypes., Conclusions: Risk of lung cancer increased as the number of deletion variants increased for GSTM1, although the associations were nonsignificant. Discriminating between the wild-type, hemizygous, and homozygous deletion GSTM1 genotypes permitted a more precise characterization of the associations between GSTM1 deletion variants and lung cancer.

Purpose: Compared to European Americans (EAs), African Americans (AAs) suffer a disproportionate share of the lung cancer mortality burden. To investigate whether this disparity in lung cancer mortality is due to differential racial risks related to socioeconomic status (education, occupation), body mass index (BMI), hypertension, or cigarette smoking, we compared associations between these factors and lung cancer mortality by race in a biracial prospective cohort study., Methods: The Charleston (South Carolina) Heart Study (N = 2,054) was established in 1960; 40% of the study participants are AAs. The participants have been followed up for mortality for 40 years. Using Cox proportional hazards models, we investigated whether there were racial differences in the associations between the study factors and lung cancer mortality., Results: Cigarette smoking was the strongest lung cancer risk factor in both races. The association between cigarette smoking and lung cancer mortality was stronger in EAs than AAs (hazards ratio [HR] 26.1 vs. 7.6). In both races, men were at significantly greater risk than women and BMI was significantly inversely associated with lung cancer mortality., Conclusions: The evidence from the present study does not yield strong clues for the excess lung cancer mortality in AAs. Our results do not support the hypothesis that differential susceptibility to cigarette smoking is a major contributor to the racial disparity in lung cancer. This suggests we must expand our scope of inquiry beyond the factors included in the present study to fully understand why lung cancer mortality rates are greater in AAs than EAs.

Accumulating evidence suggests a role for inflammation in the development and progression of cancer. Our group recently identified a cytokine gene signature in lung tissue associated with lung cancer prognosis. Therefore, we hypothesized that concentrations of circulating cytokines in serum may be associated with lung cancer survival. Ten serum cytokines, namely, interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, interferon (IFN)-gamma, and tumor necrosis factor-alpha, were assessed in 353 non-small cell lung cancer cases from a case-control study of lung cancer in the greater Baltimore, Maryland area. Cytokines were measured using an ultrasensitive electrochemiluminescence immunoassay. IL-6 serum concentrations (>or=4.0 pg/mL) were associated with significantly poorer survival in both African Americans [hazard ratio (HR), 2.71; 95% confidence interval (CI), 1.26-5.80] and Caucasians (HR, 1.71; 95% CI, 1.22-2.40). IL-10 (HR, 2.62; 95% CI, 1.33-5.15) and IL-12 (HR, 1.98; 95% CI, 1.14-3.44) were associated with lung cancer survival only in African Americans. Some evidence for an association of tumor necrosis factor-alpha levels with survival in Caucasians was observed, although these results were not significant. These hypothesis-generating findings indicate that selected serum cytokine concentrations are associated with lung cancer survival, and indicate that further research is warranted to better understand the mechanistic underpinnings of these associations.

Background: Cruciferous vegetables, rich in isothiocyanates, may protect against lung cancer. Glutathione S-transferases are important in metabolizing isothiocyanates; hence, variants in GST genes may modify the association between cruciferous vegetable intake and lung cancer. We carried out a systematic review to characterize the association between cruciferous vegetable intake and lung cancer risk, with an emphasis on the potential interaction between cruciferous vegetables and GSTM1 and GSTT1 gene variants., Methods: A search of the epidemiologic literature through December 2007 was conducted using 15 bibliographic databases without language restrictions. Thirty studies on the association between lung cancer and either total cruciferous vegetable consumption (6 cohort and 12 case-control studies) or specific cruciferous vegetables (1 cohort and 11 case-control studies) were included., Results: The risk for lung cancer among those in the highest category of total cruciferous vegetable intake was 22% lower in case-control studies [random-effects pooled odds ratio, 0.78; 95% confidence interval (95% CI), 0.70-0.88] and 17% lower in cohort studies (pooled relative risk, 0.83; 95% CI, 0.62-1.08) compared with those in the lowest category of intake. The strongest inverse association of total cruciferous vegetable intake with lung cancer risk was seen among individuals with GSTM1 and GSTT1 double null genotypes (odds ratio, 0.41; 95% CI, 0.26-0.65; P for interaction = 0.01)., Conclusions: Epidemiologic evidence suggests that cruciferous vegetable intake may be weakly and inversely associated with lung cancer risk. Because of a gene-diet interaction, the strongest inverse association was among those with homozygous deletion for GSTM1 and GSTT1.

Exposure to inorganic arsenic via drinking water is a growing public health concern. We conducted a systematic review of the literature examining the association between arsenic in drinking water and the risk of lung cancer in humans. Towards this aim, we searched electronic databases for articles published through April 2006. Nine ecological studies, two case-control studies, and six cohort studies were identified. The majority of the studies were conducted in areas of high arsenic exposure (100 microg/L) such as southwestern Taiwan, the Niigata Prefecture, Japan, and Northern Chile. Most of the studies reported markedly higher risks of lung cancer mortality or incidence in high arsenic areas compared to the general population or a low arsenic exposed reference group. The quality assessment showed that, among the studies identified, only four assessed arsenic exposure at the individual level. Further, only one of the ecological studies presented results adjusted for potential confounders other than age; of the cohort and case-control studies, only one-half adjusted for cigarette smoking status in the analysis. Despite these methodologic limitations, the consistent observation of strong, statistically significant associations from different study designs carried out in different regions provide support for a causal association between ingesting drinking water with high concentrations of arsenic and lung cancer. The lung cancer risk at lower exposure concentrations remains uncertain.

Background: Carotenoids are thought to have anti-cancer properties, but findings from population-based research have been inconsistent., Objective: We aimed to conduct a systematic review of the associations between carotenoids and lung cancer., Design: We searched electronic databases for articles published through September 2007. Six randomized clinical trials examining the efficacy of beta-carotene supplements and 25 prospective observational studies assessing the associations between carotenoids and lung cancer were analyzed by using random-effects meta-analysis., Results: The pooled relative risk (RR) for the studies comparing beta-carotene supplements with placebo was 1.10 (95% confidence limits: 0.89, 1.36; P = 0.39). Among the observational studies that adjusted for smoking, the pooled RRs comparing highest and lowest categories of total carotenoid intake and of total carotenoid serum concentrations were 0.79 (0.71, 0.87; P < 0.001) and 0.70 (0.44, 1.11; P = 0.14), respectively. For beta-carotene, highest compared with lowest pooled RRs were 0.92 (0.83, 1.01; P = 0.09) for dietary intake and 0.84 (0.66, 1.07; P = 0.15) for serum concentrations. For other carotenoids, the RRs comparing highest and lowest categories of intake ranged from 0.80 for beta-cryptoxanthin to 0.89 for alpha-carotene and lutein-zeaxanthin; for serum concentrations, the RRs ranged from 0.71 for lycopene to 0.95 for lutein-zeaxanthin., Conclusions: beta-Carotene supplementation is not associated with a decrease in the risk of developing lung cancer. Findings from prospective cohort studies suggest inverse associations between carotenoids and lung cancer; however, the decreases in risk are generally small and not statistically significant. These inverse associations may be the result of carotenoid measurements' function as a marker of a healthier lifestyle (higher fruit and vegetable consumption) or of residual confounding by smoking.

Lung cancer is the leading cause of cancer death in the world. However, there is large geographic variation internationally and within nations. Despite the fact that many causes of lung cancer have been established, cigarette smoking is the principal cause. Accounting for historical prevalence of cigarette smoking is a useful predictor of the lung cancer burden in most populations. The populations at high present risk of lung cancer can usually be predicted based on historical patterns of the prevalence of cigarette smoking, and the high-risk populations of the future can be predicted based on the current prevalence of cigarette smoking. Lung cancer rates are consistently higher among men than women and are particularly high among African American men and among those of lower socioeconomic status. At the individual level, some segments of the population (e.g., African Americans, females) have been hypothesized to have greater susceptibility to lung cancer for a given degree of cigarette smoking. Common variants in genes that encode for enzymes involved in carcinogen metabolism and detoxification and in repairing DNA damage are likely to be important determinants of interindividual susceptibility to smoking-caused lung carcinogenesis. Many lung cancer risk factors have been identified, but active cigarette smoking is the predominant cause of lung cancer and the principal marker of both high-risk populations and high-risk individuals. In the absence of cigarette smoking, lung cancer would be a rare disease. Strategies that effectively prevent youths from starting to smoke and that promote cessation among dependent smokers can transform populations from high risk to low risk.

Background: The objective of this study was to summarize the published literature concerning the epidemiology of lung cancer., Methods: A narrative review of published evidence was conducted, identifying and summarizing key reports that describe the occurrence of lung cancer in populations and factors that affect lung cancer risk., Results: In the United States, lung cancer remains the leading cause of cancer death in both men and women, even though an extensive list of modifiable risk factors has long been identified. The predominant cause of lung cancer is exposure to tobacco smoke, with active smoking causing most cases but passive smoking also contributing to the lung cancer burden., Conclusions: The reductions in smoking prevalence in men that occurred in the late 1960s through the 1980s will continue to drive lung cancer mortality rates downward in men during the first portion of this century, but rates in women have not yet begun to decrease. Fortunately, exposures to major occupational respiratory carcinogens have largely been controlled, but the population is still exposed to environmental causes of lung cancer, including radon, the second leading cause of lung cancer death.

Objective: Lung cancer is more common in HIV-infected patients than in the general population. We examined how effectively lung cancer was being diagnosed in our HIV-infected patients., Methods: Retrospective study assessing clinical diagnosis of lung cancer in HIV-infected patients at Johns Hopkins Hospital between 1986 and 2004., Results: Ninety-two patients were identified. Compared to HIV-indeterminate patients (n=4973), HIV-infected individuals were younger with more advanced cancer. CD4 counts and HIV-1 RNA levels indicated preserved immune function. Mortality was higher in HIV-infected patients, with 92% dying of lung cancer (hazard ratio, 1.57; 95% confidence interval, 1.25-1.96), compared to HIV-uninfected patients. Advanced stage and black race were associated with worse survival. After adjustment for these factors, HIV infection was not associated with increased mortality (hazard ratio, 1.04; 95% confidence interval, 0.83-1.32). Of 32 patients followed in our HIV clinic, 60% of chest radiographs had no evidence of neoplasm within 1 year of diagnosis compared to only 1 (4%) of 28 chest computed tomography scans. Nonspecific infiltrates were observed in 9 patients in the same area that cancer was subsequently diagnosed., Conclusions: HIV-infected lung cancer patients have shortened survival mainly due to advanced stage. Low clinical suspicion and overreliance on chest radiographs hindered earlier detection. Aggressive follow-up of nonspecific pulmonary infiltrates in these patients is warranted.

Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivation of checkpoint genes by genetic and epigenetic mechanisms is frequent in all cancer types, as a less-efficient cell cycle control can lead to genetic instability and tumorigenesis. In an on-going case-control study consisting of 216 patients with non-small cell lung cancer, 226 population-based controls, and 114 hospital-based controls, we investigated the relationship of gamma-radiation-induced G2-M arrest and lung cancer risk. Peripheral blood lymphocytes were cultured for 90 hours, exposed to 1.0 Gy gamma-radiation, and harvested at 3 hours after gamma-radiation treatment. gamma-Radiation-induced G2-M arrest was measured as the percentage of mitotic cells in untreated cultures minus the percentage of mitotic cells in gamma-radiation-treated cultures from the same subject. The mean percentage of gamma-radiation-induced G2-M arrest was significantly lower in cases than in population controls (1.18 versus 1.44, P < 0.01) and hospital controls (1.18 versus 1.40, P = 0.01). When dichotomized at the 50th percentile value in combined controls (population and hospital controls), a lower level of gamma-radiation-induced G2-M arrest was associated with an increased risk of lung cancer among African Americans after adjusting for baseline mitotic index, age, gender, and pack-years of smoking [adjusted odd ratio (OR), 2.25; 95% confidence interval (95% CI), 0.97-5.20]. A significant trend of an increased risk of lung cancer with a decreased level of G2-M arrest was observed (P(trend) = 0.02) among African Americans, with a lowest-versus-highest quartile adjusted OR of 3.74 (95% CI, 0.98-14.3). This trend was most apparent among African American females (P(trend) < 0.01), with a lowest-versus-highest quartile adjusted OR of 11.75 (95% CI, 1.47-94.04). The results suggest that a less-efficient DNA damage-induced G2-M checkpoint is associated with an increased risk of lung cancer among African Americans. Interestingly, we observed a stronger association of DNA damage-induced G2-M arrest and lung cancer among African Americans when compared with Caucasians. If replicated, these results may provide clues to the exceedingly high lung cancer incidence experienced by African Americans.

In the United States, the 20th century witnessed the emergence of a lung cancer epidemic that peaked and began to decline by the century's end, a decline that continues today. However, lung cancer continues to be an unabating pandemic. In research carried out over the last half of the 20th century, many factors were causally associated with lung cancer and studies were implemented to identify determinants of susceptibility to these factors. Cigarette smoking was identified as the single most predominant cause of the lung cancer epidemic, but other causes were found, including workplace agents (eg, asbestos, arsenic, chromium, nickel, and radon) and other environmental factors (passive smoking, indoor radon, and air pollution). Contemporary epidemiologic research on lung cancer now focuses on a new set of issues, primarily related to susceptibility to the well-identified causal factors, particularly smoking, and on the consequences of changes in tobacco products for risks to smokers. Diet and the possibility of reducing risk through chemoprevention remain a focus of research emphasis through experimental and observational approaches. Questions have also been raised about possible differences in susceptibility to lung cancer by sex and race. Population patterns in smoking prevalence will continue to be the most powerful predictor of the future occurrence of lung cancer. Evaluation of recent US patterns in smoking prevalence indicates that for the next approximately 10 to 15 years, lung cancer rates will decrease, but will then level off starting in approximately 2030. Unless further reductions in the prevalence of cigarette smoking are achieved over the next decade, lung cancer will remain as an all too common, but avoidable, disease.

Objective: Although resection is not the standard of care in treating small cell lung cancer, new platinum drugs and modern staging have allowed the role of surgery to be reevaluated., Methods: We reviewed our institutional experience of 1415 patients with small cell lung cancer from 1976 to 2002 among whom 82 (6%) underwent surgery with curative intent., Results: Median age at surgery was 62 years, and small cell lung cancer of mixed morphology represented 14 of 82 (17%). Treatment consisted of surgery alone in 11% of cases (9/82), surgery with neoadjuvant therapy in 22% (18/82), and surgery with adjuvant therapy in 55% (45/82). Prophylactic cranial irradiation was given to 23% (19/82). The 5-year survival of the entire cohort was 42%. The 5-year survival of patients receiving adjuvant chemotherapy (n = 41) was significantly different according to whether patients had received platinum or nonplatinum regimens (68% vs 32.2%, P = .04). Among patients with stage I disease who received adjuvant chemotherapy (n = 24), the 5-year survivals for patients receiving platinum and nonplatinum chemotherapy were 86% and 42%, respectively ( P < .02). If patients who received either neoadjuvant or adjuvant therapy (n = 56) were considered, the 5-year survival was significantly better for platinum than for nonplatinum chemotherapy (62% vs 36%, P = .05). The 5-year survival was also better for those undergoing lobectomies (n = 52) than for those with limited resections (n = 15, 50% vs 20%, P = .03). Survival outcomes also differed by gender, with female patients having a 5-year survival advantage over male patients (60% vs 28%, P = .004)., Conclusion: These results support a reevaluation of the role of surgery in the multimodality therapy for small cell lung cancer, which currently includes only radiotherapy and chemotherapy.

Background: This study was performed to test the hypothesis that a history of other primary neoplasms before a lung cancer diagnosis increases the risk of subsequent malignancy., Methods: Of 8363 lung cancer patients seen from 1978 to 2002, 881 (11%) had at least 1 previous nonlung primary malignancy. Charts were analyzed for the occurrence of subsequent malignancies., Results: Lung cancer diagnosis in 881 patients consisted of 75% non-small cell, 12% small cell, and 13% other histologies. The median age was 66 years, with 56% male, 76% white, and 86% smokers. Of the 881 patients, 92% had no subsequent cancer (group 1), and 8% went on to experience the development of a new primary neoplasm (including lung) after their lung cancer (group 2). After adequate follow-up, the cumulative probability of developing a subsequent cancer did not differ markedly between those with and without a prior non-lung cancer diagnosis at 2 years (12% vs 10%) or 5 years (16% vs 15%). Group 1 patients had a significantly lower 1- and 5-year survival than group 2 patients (59% vs 48% and 29% vs 17%, respectively; P =.008). Although multivariate analysis suggested that stage, history of tobacco-associated neoplasm, and history of definitive surgical resection were important determinants in predicting long-term survival, a prior malignancy was not an independent risk factor in the development of subsequent malignancy., Conclusions: The risk of developing a subsequent malignancy is very high in lung cancer patients with prior primary malignancies, but it is not markedly different from the risks experienced by patients with no prior malignancies.

Background: Recent reports indicate that age is not a contraindication to pulmonary resection for octogenarians with nonsmall cell lung cancer (NSCLC), but other data are lacking. The purpose of this study was to determine outcomes in these patients, particularly short- and long-term survival with stage I disease., Methods: A retrospective cohort of 68 octogenarians with NSCLC who underwent curative resection from 1980 to 2002 was followed-up for outcomes., Results: Median age was 82 years old (range, 80-87 years old) consisting of 44 males (65%), with a mean follow-up of 32 months (range, 1-178 months). Operations included: 47 lobectomies (69%), 11 wedge resections (16%), 5 segmentectomies (8%), 4 bilobectomies (6%), and 1 pneumonectomy (1%). There were 31 adenocarcinomas (46%), 18 squamous carcinomas (26%), 12 bronchioalveolar carcinomas (18%), 4 large cell carcinomas (6%), and 3 miscellaneous malignant neoplasms (4%). Median hospital stay was 7 days (range, 3-53 days). Thirty-day mortality was 8.8% (n = 6) with 83% developing cardiopulmonary complications. Overall actuarial survival at 1, 3, and 5 years was 73%, 51%, and 34%, respectively. Of 41 patients (60%) with stage I disease, 23 were T1 lesions. Five-year survival was significantly different between stages Ia and Ib patients (61% and 10%, respectively, p = 0.001). Patients in more advanced stages had a 5-year survival of 3/27 (11%). Multivariate analysis identified advanced tumor stage, lower ASA physical status, and low FEV(1) as factors associated with poorer long-term survival., Conclusions: The 5-year survival, particularly in patients with stage Ia tumors with favorable ASA and FEV(1), supports the notion that health status and tumor stage outweigh chronologic age in determining surgical candidates.

Environmental exposure to carcinogens and individual susceptibility play significant roles in cancer risk. Suboptimal DNA repair capability, measured by quantifying mutagen-induced chromosome breaks, might explain variable host susceptibility to environmental carcinogens. In an ongoing lung cancer case-control study, we compared individual sensitivity to bleomycin-induced chromosome breaks in 152 non-small cell lung cancer patients with 94 population controls and 85 hospital controls with no history of cancer. Mutagen sensitivity was measured by mean number of chromatid breaks per cell in cultured peripheral blood lymphocytes treated with bleomycin. Non-parametric tests and chi(2) tests were used to determine the statistical significance of the crude case-control comparisons, followed by logistic regression to adjust for important covariates. The mean number of bleomycin-induced breaks per cell was 1.01 for the cases compared with 0.86 for hospital controls (P < 0.01) and 0.89 for population controls (P < 0.01). The mean number of breaks per cell was 1.01 for those >65 years old and 0.81 for those < or = 65 years old (P < 0.01) among population controls. Defining bleomycin sensitive as >0.84 break/cell (the median level in population controls), 67% of the cases were bleomycin sensitive compared with 49% of the hospital controls [adjusted odds ratio (OR) = 2.69, 95% confidence interval (CI) = 1.44, 5.04], and 51% of the population controls (adjusted OR = 2.18, 95% CI = 1.13, 4.21). Our data indicate that the increased number of bleomycin-induced chromosome breaks was significantly associated with an increased risk of lung cancer in the first 331 subjects.

In the United States, lung cancer remains the leading cause of cancer death in both men and women even though an extensive list of risk factors has been well-characterized. Far and away the most important cause of lung cancer is exposure to tobacco smoke through active or passive smoking. The reductions in smoking prevalence in men that occurred in the late 1960s through the 1980s will continue to drive the lung cancer mortality rates downward in men during the first portion of this century. This favorable trend will not persist unless further reductions in smoking prevalence are achieved.

Lung cancer cases diagnosed during the period 1975 through 1993 and matched controls were identified in the rosters of Washington County, Maryland residents who had donated blood for a serum bank in 1974 or 1989. Plasma from participants in the 1989 project was assayed for ascorbic acid; serum or plasma was assayed for participants in either project for alpha- and beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Among the total group of 258 cases and 515 controls, serum/plasma concentrations were significantly lower among cases than controls for cryptoxanthin, beta-carotene, and lutein/zeaxanthin with case-control differences of -25.5, -17.1, and -10.1%, respectively. Modest nonsignificant case-control differences in a protective direction were noted for alpha-carotene and ascorbic acid. There were only trivial differences for lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Findings are reported for males and females and for persons who had never smoked cigarettes, former smokers, and current smokers at baseline. These results and those from previous studies suggest that beta-carotene is a marker for some protective factor(s) against lung cancer; that cryptoxanthin, alpha-carotene, and ascorbic acid need to be investigated further as potentially protective factors or associates of a protective factor; and that lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity are unlikely to be associated with lung cancer risk. Until specific preventive factors are identified, the best protection against lung cancer is still the avoidance of airborne carcinogens, especially tobacco smoke; second best is the consumption of a diet rich in fruits and vegetables.