Quantitative Imaging Markers of Lung Function in a Smoking Population Distinguish COPD Subgroups with Differential Lung Cancer Risk

Lusk, Christine M.; Wenzlaff, Angela S.; Watza, Donovan; Sieren, Jessica C.; Robinette, Natasha; Walworth, Garrett; Petrich, Michael; Neslund‐Dudas, Christine; Flynn, Michael J.; Song, Thomas; Spizarny, David L.; Simoff, Michael; Soubani, Ayman O.; Gadgeel, Shirish M.; Schwartz, Ann G.

doi:10.1158/1055-9965.epi-18-0886

“…Current clinical TKIs that target EGFR mutations include erlotinib, getfitnib, and afatinib ( Maemondo et al, 2010 ; Zhou et al, 2011 ; Sequist et al, 2013 ; Greathouse et al, 2018 ; Lusk et al, 2019b ). As mentioned previously, studies have shown that identifying the type of EGFR mutation a patient harbors in their NSCLC tumors may have significant clinical value in predicating response.…”

Section: Discussionmentioning

confidence: 99%

A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US

James

¹

,

Williams

²

,

Nemesure

³

2023

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Background: Non-Small Cell Lung Cancer (NSCLC), the leading cause of cancer-related death in the United States, is the most diagnosed form of lung cancer. While lung cancer incidence has steadily declined over the last decade, disparities in incidence and mortality rates persist among African American (AA), Caucasian American (CA), and Hispanic American (HA) populations. Researchers continue to explore how genetic ancestry may influence differential outcomes in lung cancer risk and development. The purpose of this evaluation is to highlight experimental research that investigates the differential impact of genetic mutations and ancestry on NSCLC incidence.Methods: This systematic review was conducted using PubMed and Google Scholar search engines. The following key search terms were used to select articles published between 2011 and 2022: “African/European/Latin American Ancestry NSCLC”; “Racial Disparities NSCLC”; “Genetic Mutations NSCLC”; “NSCLC Biomarkers”; “African Americans/Hispanic Americans/Caucasian Americans NSCLC incidence.” Systematic reviews, meta-analyses, and studies outside of the US were excluded. A total of 195 articles were initially identified and after excluding 156 which did not meet eligibility criteria, 38 were included in this investigation.Results: Studies included in this analysis focused on racial/ethnic disparities in the following common genetic mutations observed in NSCLC: KRAS, EGFR, TP53, PIK3CA, ALK Translocations, ROS-1 Rearrangements, STK11, MET, and BRAF. Results across studies varied with respect to absolute differential expression. No significant differences in frequencies of specific genetic mutational profiles were noted between racial/ethnic groups. However, for HAs, lower mutational frequencies in KRAS and STK11 genes were observed. In genetic ancestry level analyses, multiple studies suggest that African ancestry is associated with a higher frequency of EGFR mutations. Conversely, Latin ancestry is associated with TP53 mutations. At the genomic level, several novel predisposing variants associated with African ancestry and increased risk of NSCLC were discovered. Family history among all racial/ethnic groups was also considered a risk factor for NSCLC.Conclusion: Results from racially and ethnically diverse studies can elucidate driving factors that may increase susceptibility and subsequent lung cancer risk across different racial/ethnic groups. Identification of biomarkers that can be used as diagnostic, prognostic, and therapeutic tools may help improve lung cancer survival among high-risk populations.

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“…14 Some studies, however, have proposed that the variance in lung function measures among smokers is not fully explained by the smoking intensity and the number of pack-years smoked did not affect the lung cancer rate in patients with COPD. 15 A study in 2017 16 said the annual frequency of lung cancer in never-smokers had more than doubled in the past 7 years, from 13% to 28%. This increase was due to an absolute increase in the number of never-smokers developing lung cancer, not simply a change in the ratio of never-smokers to current and former smokers.…”

Section: Why This Study Addsmentioning

confidence: 99%

Impaired lung function and lung cancer risk in 461 183 healthy individuals: a cohort study

Kyaw,

Tsai,

Wen

et al. 2024

BMJ Open Resp Res

0

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BackgroundIt has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as preserved ratio impaired spirometry (PRISm) and airflow obstruction (AO), on the incidence and mortality of lung cancer in both general and never-smoker populations remains unclear. We wished to examine the effect of lung function impairments on lung cancer risks.MethodsThis was a retrospective cohort study (1 January 1994 to 31 December 2017) of individuals from a health surveillance programme in Taiwan who underwent baseline spirometry tests at the entry point. PRISm was defined as an FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio >0.7 and FEV1<0.8, while AO was defined as an FEV1/FVC ratio <0.7. Cox proportional hazards models and cubic spline curves were used to examine the associations between lung function impairments and lung cancer risks.ResultsThe study included 461,183 individuals, of whom 14.3% had PRISm and 7.9% had AO. A total of 4038 cases of lung cancer and 3314 lung cancer-related deaths were identified during the 23 years of follow-up. Individuals with PRISm and AO exhibited a higher risk of lung cancer incidence and mortality compared with those with normal lung function. The adjusted HRs and 95% CIs were 1.14 (1.03 to 1.26) and 1.23 (1.10 to 1.37) in the overall cohort, and 1.08 (0.93 to 1.24), and 1.23 (1.05 to 1.45) in the never-smoker cohort. The risks of both developing and dying of lung cancer increased with the severity levels of lung function impairments and lower FEV1values.ConclusionImpaired lung function is associated with increased risks of developing lung cancer and subsequent mortality. The study highlights the importance of considering lung function in lung cancer screening for better candidate selection.

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“…[14] Some studies, however, have proposed that the variance in lung function measures among smokers is not fully explained by the smoking intensity and the number of pack-years smoked did not affect the lung cancer rate in patients with COPD. [15]…”

Section: Introductionmentioning

confidence: 99%

Impaired lung function and lung cancer risk in 461,183 healthy individuals: a cohort study

Kyaw,

Tsai,

Wen

et al. 2023

Preprint

0

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BackgroundIt has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as preserved ratio impaired spirometry (PRISm) and airflow obstruction (AO), on the incidence and mortality of lung cancer in both general and never-smoker populations remains unclear. We wished to examine the effect of lung function impairments on lung cancer risks.MethodsThis was a retrospective cohort study of individuals from a health surveillance program in Taiwan who underwent baseline spirometry tests at the entry point. PRISm was defined as an FEV1/FVC (Forced Expiratory Volume in 1 second/ Forced Vital Capacity) ratio >0.7 and FEV1 <0.8, while AO was defined as an FEV1/FVC ratio <0.7. Cox proportional hazards models and cubic spline curves were used to examine the associations between lung function impairments and lung cancer risks.ResultsThe study included 461,183 individuals, of whom 14.3% had PRISm and 7.9% had AO. A total of 4,038 cases of lung cancer and 3,314 lung cancer-related deaths were identified during the 23 years of follow-up. Individuals with PRISm and AO exhibited a higher risk of lung cancer incidence and mortality compared to those with normal lung function. The adjusted hazard ratios (aHRs) and 95% confidence intervals (95%CI) were 1.14 (1.03-1.26) and 1.23 (1.10-1.37) in the overall cohort, and 1.08 (0.93-1.24), and 1.23 (1.05-1.45) in the never-smoker cohort. The risks of both developing and dying of lung cancer increased with the severity levels of lung function impairments and lower FEV1 values.ConclusionImpaired lung function is associated with increased risks of developing lung cancer and subsequent mortality. The study highlights the importance of considering lung function in lung cancer screening for better candidate selection.WHAT IS ALREADY KNOWN ON THIS TOPICImpaired lung function is a common condition that can be observed in people with smoking habits and other respiratory illnesses including lung cancer. However, the effect of lung function impairment alone on the risks of lung cancer incidence and mortality is not clear. Early detection of lung cancer is essential for effective disease management, and lung cancer screening is a key preventive measure that can help achieve this. However, current lung cancer screening guidelines only consider age and smoking history, not lung function status.WHY THIS STUDY ADDSImpaired lung function is associated with an increased risk of lung cancer in a large Asian cohort. Nonetheless, among never-smoking individuals exhibiting spirometrically defined PRISM/AO, the observed risks were found to lack statistical significance, with the exception of lung cancer mortality within the non-smoking PRISm subgroup.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYLung function status should be taken into consideration in lung cancer screening criteria. The importance of monitoring and addressing lung function impairment in lung cancer risk management should also be widely shared with the medical community and the public.

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Quantitative Imaging Markers of Lung Function in a Smoking Population Distinguish COPD Subgroups with Differential Lung Cancer Risk

Cited by 5 publications

References 23 publications

A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US

A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US

Impaired lung function and lung cancer risk in 461 183 healthy individuals: a cohort study

Impaired lung function and lung cancer risk in 461,183 healthy individuals: a cohort study

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