Does Vertical Density Affect Lung Cancer Mortality Differently for Men and Women?

Some studies have suggested a protective effect of antioxidant nutrients on lung cancer. Observational epidemiological studies suggest an association between higher dietary levels of fruits and vegetables containing beta carotene and a lower risk of lung cancer. To determine whether vitamins, minerals and other potential agents, alone or in combination, reduce incidence and mortality from lung cancer in healthy people. The electronic databases MEDLINE (1966-july 2001), EMBASE (1974-july 2001) and the Cochrane Controlled Trial Register (CENTRAL, Issue 3/2001) and bibliographies were searched. In addition authors of included studies were contacted to identify potentially eligible published and unpublished trials. Included studies were randomised controlled clinical trials comparing different supplements or comparing supplements with placebo, administered to healthy people with the aim of preventing lung cancer. Three reviewers independently selected the trials to be included in the review and assessed the methodological quality of each trial, and two extracted data using a standardised form. For each study, relative risk and 95% confidence limits were calculated for dichotomous outcomes. Four studies were eligible for inclusion. All were population based trials, including a total of 109,394 participants. Two studies included smokers, one included workers exposed to asbestos and two studies were carried out in health professionals. A group of participants with no known risk factors for lung cancer was included in the study sample of two trials. Beta-carotene was evaluated in all trials, alone or combination with alpha-tocopherol or retinol, and one study tested alpha-tocopherol alone. Duration of treatment varied from 2 to 12 years and follow-up was from two to five years. All trials had a placebo group. For people with risk factors for lung cancer no reduction in lung cancer incidence or mortality was found in those taking vitamins alone compared with placebo (incidence of lung cancer: RR 0.98, 95% CI 0.81-1.19; lung cancer mortality: RR 0.93, 95% CI 0.73-1.19). For people with no known risk factors of lung cancer, none of the vitamins or their combinations appeared to have any effect. Combined data from three studies showed a non-statistically significant increased risk of lung cancer incidence (RR 1.11, 95% CI 0.94-1.33) and mortality (RR 1.05, 95% CI 0.87-1.28) for beta-carotene alone at pharmacological doses in groups with risk factors for lung cancer. When beta-carotene was combined with retinol, data from a single study showed that there was a statistically significant, increased risk of lung cancer incidence (RR 1.42, 95% CI 1.13-1.80) and mortality (RR 1.75, 95% CI 1.29-2.38) in people with risk factors for lung cancer who took both vitamins compared with those who took placebo. Data from also from one study showed that the combination of beta-carotene with alpha-tocopherol in people with risk factors for lung cancer was associated with a non-statistically significant increased risk of lung cancer incidence (RR 1.16, 95% CI 0.96-1.39) and mortality (RR 1.15, 95% CI 0.91-1.45). No effect was observed for total cancer incidence, mortality or all-cause mortality. There is currently no evidence to support recommending vitamins such as alpha-tocopherol, beta-carotene or retinol, alone or in combination, to prevent lung cancer. A harmful effect was found for beta-carotene with retinol at pharmacological doses in people with risk factors for lung cancer (smoking and/or occupational exposure to asbestos). More research from larger trials and with longer follow-up is needed to analyse the effectiveness of other supplements.

Informing Patient Surveillance for the Growing Number of Survivors of Lung Cancer

<p>Supplementary Table S1. Leading causes of death among females worldwide, 2012 Number of deaths for top ten causes of death among females worldwide Supplementary Table S2. Leading causes of death among females by world region, 2012 Number of deaths for top ten causes of death among females by world region Supplementary Table S3. Estimated number of new cancer cases and deaths among females by world area, 2012 Number of cancer cases and deaths for all cancer sites combined among females by world region Supplementary Figure S1. Female breast cancer incidence and mortality rates, age-standardized rate (world), 2012 Two world maps: age-standardized breast cancer incidence rates among females and age-standardized breast cancer mortality rates among females Supplementary Figure S2. Female breast cancer incidence trends, age-standardized rate (world), select countries, 1973-2012 Observed age-standardized female breast cancer incidence rates, select countries, all ages, 1973-2012 Supplementary Figure S3. Female breast cancer survivors diagnosed in last five years (through 2012 or latest available) World map: number of breast cancer survivors diagnosed within the last five years, per 100,000 population Supplementary Figure S4. Cervical cancer incidence and mortality rates, age-standardized rate (world), 2012 Two world maps: age-standardized cervical cancer incidence rates and age-standardized cervical cancer mortality rates Supplementary Figure S5. Prevalence (%) of cervical HPV infection among women by region, all types combined, 1995-2009 World map of HPV prevalence (%) among women by world region Supplementary Table S6. Cervical cancer incidence trends, age-standardized rate (world), select countries, 1975-2007 Observed age-standardized cervical cancer incidence rates with a five-year moving average, select countries, all ages, 1975-2007 Supplementary Figure S7. Cervical cancer survivors diagnosed in last five years (through 2012 or latest available) World map: number of cervical cancer survivors diagnosed within the last five years, per 100,000 population Supplementary Figure S8. Uterine corpus cancer incidence and mortality rates, females, age-standardized rate (world), 2012 Two world maps: age-standardized uterine corpus cancer incidence rates and age-standardized uterine corpus cancer mortality rates Supplementary Figure S9. Uterine corpus cancer mortality trends, age-standardized rate (world), select countries, 1990-2014 Observed age-standardized uterine corpus cancer mortality rates with a five-year moving average, select countries, all ages, 1990-2014 Supplementary Figure S10. Ovarian cancer incidence and mortality rates, females, age-standardized rate (world), 2012 Two world maps: age-standardized ovarian cancer incidence rates and age-standardized ovarian cancer mortality rates Supplementary Figure S11. Ovarian cancer mortality trends, age-standardized rate (world), select countries, 1980-2014 Observed age-standardized ovarian cancer mortality rates with a five-year moving average, select countries, all ages, 1980-2014 Supplementary Figure S12. Colorectal cancer incidence and mortality rates, females, age-standardized rate (world), 2012 Two world maps: age-standardized liver cancer incidence rates among females and age-standardized liver cancer mortality rates among females Supplementary Figure S13. Colorectal cancer incidence trends, females, select countries, 1980-2014 Observed age-standardized colorectal cancer incidence rates among females with a five-year moving average, select countries, all ages, 1980-2014 Supplementary Figure S14. Colorectal cancer mortality trends, females, age-standardized rate (world), select countries, 1975-2014 Observed age-standardized colorectal cancer mortality rates among females with a five-year moving average, select countries, all ages, 1975-2014 Supplementary Figure S15. Lung cancer incidence and mortality rates, females, age-standardized rate (world), 2012 Two world maps: age-standardized lung cancer incidence rates among females and age-standardized lung cancer mortality rates among females Supplementary Figure S16. Population using solid fuels for heating and/or cooking, 2013 World map: percent of the population using solid fuels by country Supplementary Figure S17. Adult female smoking prevalence, age 15+ years, 2013 World map: percent of adult females (age 15+ years) who smoke by country, 2013 Supplementary Figure S18. Female youth smoking prevalence, age 13-15 years, 2011 or latest available data World map: percent of female youth (age 13-15 years) who smoke by country, 2011 or latest available data Supplementary Figure S19. Liver cancer incidence and mortality rates, females, age-standardized rate (world), 2012 Two world maps: age-standardized liver cancer incidence rates among females and age-standardized liver cancer mortality rates among females Supplementary Figure S20. Hepatitis B virus prevalence, both sexes, from systematic review of studies 1957-2013 World map of HBV prevalence (%) among both sexes combined by country Supplementary Figure S21. Estimated hepatitis C virus prevalence, both sexes, 2005 World map of HCV prevalence (%) among both sexes combined by country Supplementary Figure S22. Liver cancer mortality trends, females, age-standardized rate (world), select countries, 1995-2014 Observed age-standardized liver cancer mortality rates among females with a five-year moving average, select countries, all ages, 1995-2014</p>

BackgroundPrior research has not examined the connection between the quality of macronutrients and the occurrence as well as fatality rates of lung cancer (LC). Consequently, to delve deeper into the correlations between macronutrient quality and the likelihood of developing LC, we carried out an extensive, long-term prospective cohort study of 101,755 American adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.MethodsOur research cohort comprised 154,887 adults, aged between 55 and 74, who were enrolled from 10 screening facilities across the United States. The macronutrient quality index (MQI) was derived from participants’ responses to a dietary history questionnaire (DHQ). To quantify the strength and precision of the relationships between MQI and the incidence as well as mortality of LC, we employed Cox proportional hazards regression modeling to estimate hazard ratios (HRs) alongside their corresponding 95% confidence intervals (CIs). Additionally, we conducted subgroup analyses to scrutinize whether the observed link between MQI and LC risk was subject to modification by potential confounding variables. To reinforce the reliability of our results, sensitivity analyses were also carried out.ResultsOver an average follow-up period spanning 8.82 ± 1.95 years (accumulating to 897,809 person-years of observation), we recorded 1,706 LC diagnoses, encompassing 1,464 cases of non-small cell lung cancer (NSCLC) and 242 cases of small cell lung cancer (SCLC). Additionally, there were 1,217 deaths attributed to LC, with 1,005 NSCLC-related and 212 SCLC-related fatalities. Our results demonstrate a distinct, statistically significant inverse association between a higher MQI and both a reduced incidence (HR Q4 vs. Q1: 0.65; 95% CI: 0.56–0.76; p < 0.001 for trend) and decreased mortality (HR Q4 vs. Q1: 0.71; 95% CI: 0.60–0.84; p < 0.001 for trend) of LC. This inverse relationship held true for both NSCLC and SCLC subtypes. The robustness of the associations between MQI and the incidence as well as mortality of LC was solidly affirmed through sensitivity analyses.ConclusionOur research outcomes imply that prioritizing the intake of higher-quality macronutrients could serve as a viable strategy to mitigate LC risk within the American population.

The Mayak Production Association (MPA) worker registry has shown evidence of plutonium-induced health effects. Workers were potentially exposed to plutonium nitrate [(239)Pu(NO(3))(4)] and plutonium dioxide ((239)PuO(2)). Studies of plutonium-induced health effects in animal models can complement human studies by providing more specific data than is possible in human observational studies. Lung, liver, and bone cancer mortality rate ratios in the MPA worker cohort were compared to those seen in beagle dogs, and models of the excess relative risk of lung, liver, and bone cancer mortality from the MPA worker cohort were applied to data from life-span studies of beagle dogs. The lung cancer mortality rate ratios in beagle dogs are similar to those seen in the MPA worker cohort. At cumulative doses less than 3 Gy, the liver cancer mortality rate ratios in the MPA worker cohort are statistically similar to those in beagle dogs. Bone cancer mortality only occurred in MPA workers with doses over 10 Gy. In dogs given (239)Pu, the adjusted excess relative risk of lung cancer mortality per Gy was 1.32 (95% CI 0.56-3.22). The liver cancer mortality adjusted excess relative risk per Gy was 55.3 (95% CI 23.0-133.1). The adjusted excess relative risk of bone cancer mortality per Gy(2) was 1,482 (95% CI 566.0-5686). Models of lung cancer mortality based on MPA worker data with additional covariates adequately described the beagle dog data, while the liver and bone cancer models were less successful.

Hypomethylation of cg05575921 in the aryl-hydrocarbon receptor repressor (AHRR) gene is consistently and strongly associated with higher exposure to smoking (e.g., current smoking, greater number of pack years, and less time since quitting). Although cg05575921 hypomethylation has been reported to be associated with lung cancer risk and mortality, this has not been explored within heavy smokers or by histotype. We assessed cg05575921 methylation for associations with smoking behavior, prospective lung cancer risk, and mortality in 313 cases and controls from the Beta Carotene and Retinol Efficacy Trial (CARET) with ≥20 pack years of smoking and matched on age (±5 years), sex, race/ethnicity, enrollment year, smoking status, occupational asbestos exposure, and follow-up time. Methylation of cg05575921 in blood collected on average 4.3 years prior to diagnosis in cases was assayed using the 850K Illumina EPIC array. Quintiles of cg05575921 methylation were defined based on the control distribution, with the lowest quintile (Q1, referent) representing hypermethylation and the highest (Q5), hypomethylation. Among controls, increasing quintiles of cg05575921 hypomethylation were associated with current smoking status (Cochran-Armitage trend p=3.0 × 10-21), and with decreasing years since last smoked, increasing cigarettes per day, and decreasing body mass index (BMI) (ordinal ANOVA p=3.1 × 10-21, 1.3 × 10-17, and 0.002, respectively). We observed similar patterns in cases. We evaluated associations between cg05575921 methylation and lung cancer risk using logistic regression models conditioned on matching factors and adjusted for age, years since quit, and BMI. We evaluated cg05575921 methylation and lung cancer-specific mortality using Cox proportional hazards models adjusted for stage, age, sex, race, smoking status, intervention arm, asbestos exposure, and pack years smoked. We did not observe clear patterns of associations between cg05575921 methylation and lung cancer risk overall or by histotype. However, we found a linear relationship (p=0.03) between increasing cg05575921 hypomethylation and overall lung cancer mortality, with Q5 vs Q1 Hazard Ratio (HR)=1.60 (95% Confidence Interval (95% CI): 1.00-2.57) for mortality from lung cancer overall, and HR=2.09, 95% CI: 0.96-4.54 for adenocarcinoma (N=121). Our findings provide preliminary support that even among heavy smokers, cg05575921 hypomethylation is associated with more recent and extensive exposure to cigarette smoking, and that prediagnosis cg05575921 hypomethylation in lung cancer cases is associated with an increased hazard of death. However, since the CARET population represents a group who would largely qualify for lung cancer screening with annual low-dose computed tomography per the United States Preventive Task Force guidelines, our results do not provide support for the use of cg05575921 hypomethylation as an indicator for screening-based lung cancer risk stratification. Citation Format: Stefan Graw, Matt J. Barnett, Mark D. Thornquist, Gary E. Goodman, Chu Chen, Devin C. Koestler, Carmen J. Marsit, Jennifer A. Doherty, Laurie Grieshober. AHRR hypomethylation in heavy smokers: Associations with lung cancer risk and mortality [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr A20.

Lung cancer screening using low-dose CT: The current national landscape

To describe how snus use has reduced smoking among men in Sweden, and to estimate how smoking-attributable lung cancer mortality would decline in other European Union countries if they had the smoking prevalence of Sweden. Lung cancer mortality rates (LCMRs) and numbers of deaths among men and women age 45+ years in 25 EU countries in 2002 were obtained from the World Health Organization mortality database, and the number of lung cancer deaths expected in each country at the LCMR of Sweden was calculated. LCMRs for EU countries were obtained during the period 1950-2004, and per capita consumption of nicotine from cigarettes and snus was estimated for men in Sweden from 1931 to 2004. There were 172,000 lung cancer deaths among men in the EU in 2002. If all EU countries had the LCMR of men in Sweden, there would have been 92,000 (54%) fewer deaths. In contrast, the LCMR among Swedish women was the sixth highest in the EU; at the Swedish rate, deaths among EU women would have increased by 14,500 (26%). These LCMR patterns were in place for most of the last 50 years, and LCMRs among Swedish men can be correlated with snus and cigarette consumption. This study shows that snus use has had a profound effect on smoking prevalence and LCMRs among Swedish men. While it cannot be proven that snus would have the same effect in other EU countries, the potential reduction in smoking-attributable deaths is considerable.

Objective: Lung cancer (LC) is one of the most common cancers and the main causes of cancer mortality in the world. The aim of this study was to investigate the epidemiology of lung cancer incidence and mortality in 185 countries and its relationship with the HDI index in 2018. Materials and Methods: This is a descriptive-analytic study conducted on the extraction of incidence data and mortality rates of cancers from Cancer World Bank in 2018. The incidence and mortality rates and lung cancer distribution maps were drawn for World countries. To analyze the data, the correlation and regression tests were used to evaluate the correlation between the incidence and mortality with HDI. The statistical analysis was conducted by Stata-14 and the significance level was estimated at the level of 0.05. Results: With 209,386 new cases (12.22 per 100,000) and 1,761,007 deaths (19.88 per 100,000), lung cancer has the highest incidence and mortality rate in the world. The highest incidence rate (56.7 per 100,000) and mortality (44.4 per 100,000) of lung cancer were in Hungary. According to a projection, the incidence and mortality rate of lung cancer are expected to increase from 2018 to 2040, and the results showed that there was a positive and significant correlation between incidence (R=0.724, p<0.001) and mortality (R=0.702, p<0.001) of lung cancer with HDI in both sexes. The linear regression model showed that the increase in MYS (B=1.3, p<0.05) and LBE (B=0.3, p<0.05) increased the incidence of lung cancer (p<0.05), and also the increase in HDI, MYS, LEB, and EYS were caused by increases in mortality, but the increase was not statistically significant (p> 0.05). Conclusions: With the highest global incidence, motility, and an upward trend by 2040, lung cancer has a considerable global importance, and the human development index (HDI) can be an important factor in reducing the incidence and mortality of patients.

Background. Lung cancer is the number one cause of cancer-related deaths in the U.S. and many other countries. Lung cancer incidence and mortality rates have decreased for all races over the past 20 years, in part because of decreased tobacco use. Yet, there have been few clinical studies of lung cancer morbidity and mortality by race. The purpose of this study is to examine racial differences in lung cancer mortality in the U.S. using the electronic health records (EHR) database, TriNetX. Method. This retrospective cohort study was conducted based on the data from US Collaborative Network in TriNetX, a real-time, EHR database providing 42.7-million patient data from 49 health care organizations (HCOs). The cohort of interest was lung cancer patients in the U.S., which were identified using the ICD-10 code of C34 with an index diagnosis date of January 1, 2010. Kaplan-Meier curves, log-rank chi-square statistics, and hazard ratio (HR) were compared among different racial groups in the EHR data. Results. Of 42.7-million patients in the U.S., the majority (60.3%) were people who are non-Hispanic white (NHW) followed by people who are Black/African American (15.4%), Hispanic (7.2%), Asian (4.6%), and others (Native Hawaiian/Pacific Islander, 0.5%). 394,560 lung cancer patients were identified. Kaplan-Meier survival curves showed that Asians had the highest survival probability with median overall survival (OS) from the initial lung cancer diagnosis of 127.3 months, compared to 92.1 months for Hispanic, 69.1 months for African American/Black, 61.4 months for others, and 53.8 months for NHW. The HR was highest among NHW (HR=1.71, 95% CI=1.62-1.81), others (HR=1.62, 95% CI=1.41-1.85), African American/Black (HR=1.52, 95% CI=1.43-1.61), and Hispanic patients (HR=1.40, 95% CI=1.30-1.52) compared to Asian patients Conclusion. These findings suggest racial disparities in lung cancer survival, with NHW having the lowest and Asians having the highest median survival. These findings are inconsistent with the results from the Multiethnic Cohort study (prospective population based study), which reported blacks having the lowest median survival. It indicates that there are different racial burdens of lung cancer from clinical data and population data. Further analyses are needed to adjust potential confounders such as smoking status and stage of diagnosis. Citation Format: SoHye Park, Zachary Urdang, Julie Barta, Kuang-Yi Wen, Joseph Curry, Hee-Soon Juon. Racial differences in lung cancer burden: A retrospective analysis of TriNetX data [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A023.

Lung and bronchus cancer, collectively called lung cancer, remains one of the most lethal malignancies worldwide, with its incidence and mortality rates continuing to pose significant public health challenges. Numerous studies have explored various risk factors for lung cancer, including smoking, environmental pollutants, genetic predispositions, and occupational hazards. However, emerging research suggests that elevation above sea level may also influence lung and bronchus cancer prevalence and outcomes. We analyzed elevation data for 2662 contiguous U.S. counties to determine if there is a significant relationship between lung cancer and elevation. Moreover, we employed hierarchical multiple regression and a complex sample general linear model (CSGLM) to enhance the understanding of the factors influencing lung and bronchus cancer, with a particular focus on elevation. Using Local Moran’s I cluster analysis, we identified statistically significant hot spots and cold spots for the mortality rate related to lung cancer. In the hierarchical regression model, a significant correlation between lung cancer and elevation remained evident. This suggests that the risk of mortality from lung and bronchus cancer increases with decreasing elevation (R2 = 0.601). Furthermore, within the CSGLM framework, an R2 value of 0.763 highlighted a strong link between lung cancer mortality and elevation. This relationship remained significant even after accounting for complex sample designs and applying weight adjustments. This geographic correlation has not been documented in previous studies. Further research is necessary to elucidate the precise mechanisms through which elevation influences lung cancer biology.

Low-dose computed tomography (LDCT) screening is effective in reducing lung cancer mortality in smokers; however, the evidence in nonsmokers is scarce. This study aimed to evaluate the participant rate and effectiveness of one-off LDCT screening for lung cancer among smokers and nonsmokers. A population-based prospective cohort study was performed to enroll participants aged between 40 and 74 years from 2013 to 2019 from 4 cities in Zhejiang Province, China. Participants who were evaluated as having a high risk of lung cancer from an established risk score model were recommended to undergo LDCT screening. Follow-up outcomes were retrieved on June 30, 2020. The uptake rate of LDCT screening for evaluated high-risk participants and the detection rate of early-stage lung cancer (stage 0-I) were calculated. The lung cancer incidence, lung cancer mortality, and all-cause mortality were compared between the screened and nonscreened groups. At baseline, 62.56% (18,818/30,079) of smokers and 6% (5483/91,455) of nonsmokers were identified as high risk (P<.001), of whom 41.9% (7885/18,818) and 66.31% (3636/5483) underwent LDCT screening (P<.001), respectively. After a median follow-up of 5.1 years, 1100 lung cancer cases and 456 all-cause death cases (116 lung cancer death cases) were traced. The proportion of early-stage lung cancer among smokers was 60.3% (173/287), which was lower than the proportion of 80.3% (476/593) among nonsmokers (P<.001). Among smokers, a higher proportion was found in the screened group (72/106, 67.9%) than the nonscreened group (56/114, 49.1%; P=.005), whereas no significance was found (42/44, 96% vs 10/12, 83%; P=.20) among nonsmokers. Compared with participants who were not screened, LDCT screening in smokers significantly increased lung cancer incidence (hazard ratio [HR] 1.39, 95% CI 1.09-1.76; P=.007) but reduced lung cancer mortality (HR 0.52, 95% CI 0.28-0.96; P=.04) and all-cause mortality (HR 0.47, 95% CI 0.32-0.69; P<.001). Among nonsmokers, no significant results were found for lung cancer incidence (P=.06), all-cause mortality (P=.89), and lung cancer mortality (P=.17). LDCT screening effectively reduces lung cancer and all-cause mortality among high-risk smokers. Further efforts to define high-risk populations and explore adequate lung cancer screening modalities for nonsmokers are needed.

背景与目的近年来肺癌发病率和死亡率不断上升，已成为我国恶性肿瘤的首位死因。本研究旨在探讨厦门市居民肺癌死亡和减寿的变化趋势，以期为厦门市肺癌综合防治工作提供依据。方法收集整理2005年-2014年厦门市居民肺癌死亡资料计算死亡率、平均减寿年数（average potential life lost, AYLL）、死亡率年均变化百分比等评价指标，用GM（1, 1）模型对死亡率和AYLL进行预测。结果2005年-2014年，厦门市居民肺癌死亡率28.58/10万，年均上升4.86%，男性死亡率是女性的2.90倍；AYLL为7.8年，存在下降趋势。GM（1, 1）模型预测值与实际值平均相对误差2.16%-8.83%，预测2015年-2019年肺癌死亡率和AYLL值均有所上升。结论厦门市肺癌死亡率逐年升高，未来肺癌死亡率和人均减寿数都有上升趋势，应重视肺癌的预防控制工作。

Region II of Chile (the second most northerly administrative region) experienced dramatic increases in average arsenic water concentrations beginning in 1958, followed by marked declines in the 1970s when water treatment plants were installed. This history provides a unique opportunity to study time trends in the development of arsenic-related cancers, including lung and bladder cancers. We investigated lung and bladder cancer mortality from 1950 to 2000 for region II compared with region V, where drinking water was not contaminated with arsenic. Mortality data were obtained from 218,174 death certificates for the two regions for 1950-1970 and from mortality data tapes that identified 307,541 deaths in the two regions for 1971-2000. Poisson regression models were used to identify time trends in rate ratios (RRs) of mortality from lung and bladder cancers comparing region II with region V. Lung and bladder cancer mortality rate ratios for region II compared with region V started to increase about 10 years after high arsenic exposures commenced and continued to rise until peaking in 1986-1997. The peak lung cancer mortality RRs were 3.61 (95% confidence interval [CI] = 3.13 to 4.16) for men and 3.26 (95% CI = 2.50 to 4.23) for women. The peak bladder cancer RRs were 6.10 (95% CI = 3.97 to 9.39) for men and 13.8 (95% CI = 7.74 to 24.5) for women. Combined lung and bladder cancer mortality rates in region II were highest in the period 1992-1994, with mortality rates of 153 and 50 per 100,000 men and women, respectively, in region II compared with 54 and 19 per 100,000 in region V. Such large increases in total population cancer mortality rates have, to our knowledge, not been documented for any other environmental exposure. The long latency pattern is noteworthy, with mortality from lung and bladder cancers continuing to be high until the late 1990s, even though major decreases in arsenic exposure occurred more than 25 years earlier.

Background Lung cancer (LC) and respiratory failure (RF) are leading causes of adult mortality worldwide. Analyzing long‐term mortality trends across demographic, racial, geographic, and socioeconomic groups is essential to address disparities and enhance outcomes. This study investigates US national mortality patterns for LC and RF from 1999 to 2023, focusing on changes in age‐adjusted mortality rates (AAMRs) and key disparities. Methods Mortality data from the CDC WONDER database (1999–2023) for adults aged 25+ with LC (ICD‐10: C34) or RF (ICD‐10: J96) were analyzed. AAMRs per 100,000 were calculated, stratified by gender, race/ethnicity, region, state, and urban–rural status. Temporal trends were assessed using Joinpoint regression to estimate annual percent changes (APCs) with 95% confidence intervals (CIs), with significance at p &lt; 0.05. Results Over 1999–2023, 456,325 deaths from LC and RF were recorded. AAMRs declined from 1999 to 2010 (APC = −1.2, 95% CI: −1.6 to −0.9) but rose from 2010 to 2023 (APC = 1.4, 95% CI: 1.1–1.7). Men's AAMRs steadily decreased, whereas women's dropped initially, then increased from 2011 to 2023 (APC = 2.0, 95% CI: 1.7 to 2.5). Non‐Hispanic Whites saw a sharp AAMR rise from 2014 to 2017 (APC = 2.7, 95% CI: 0.9 to 3.3), with other racial/ethnic groups showing mixed trends. Regionally, the Northeast had the highest AAMRs (8.6, 95% CI: 8.5 to 8.7), and the Midwest the lowest (7.1, 95% CI: 7.0 to 7.1). Metropolitan areas saw increases post‐2006, whereas nonmetropolitan areas rose after 2009 (APC = 2.3, 95% CI: 1.8–3.1). Mississippi had the highest state AAMR (14.0, 95% CI: 13.7–14.4), Wisconsin the lowest (3.7, 95% CI: 3.5–3.8). Conclusion LC and RF mortality declined until 2010, then increased, revealing significant disparities. Targeted interventions are critical to address these trends and reduce inequities.