The Cytokinesis-Blocked Micronucleus Assay as a Strong Predictor of Lung Cancer: Extension of a Lung Cancer Risk Prediction Model

El‐Zein, Randa; Lopez, Mirtha S.; D’Amelio, Anthony M.; Liu, Mei; Munden, Reginald F.; Christiani, David C.; Su, Li; Tejera, Paula; Zhai, Rihong; Spitz, Margaret R.; Etzel, Carol J.

doi:10.1158/1055-9965.epi-14-0462

Cited by 38 publications

(24 citation statements)

References 39 publications

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“…In the BP-treated group, the shapes of the nuclei were altered together with the disruption of nuclear envelope and lamina. This may be correlated with the formation of micronuclei as be evident in the micronucleus assay (9). Mitochondria were found to be swollen, elongated and filled with flocculent material, giving a denser appearance.…”

Section: Discussionmentioning

confidence: 92%

Ultrastructural changes during lung carcinogenesis-modulation by curcumin and quercetin

Wang

Zhang

et al. 2016

Oncology Letters

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The aim of the present study was to examine the effectiveness of curcumin and quercetin in modulating ultrastructural changes during lung carcinogenesis. A total of 24 male laka mice were divided into the normal control, benzo[a]pyrene (BP)-treated, BP+curcumin-treated, BP+quercetin- treated, and BP+curcumin+quercetin-treated groups (n=6 per group). Lung carcinogenesis was induced by a single intraperitoneal injection of BP [100 mg/kg of body weight (b.wt.)]. Curcumin was supplemented to mice at a dose level of 60 mg/kg of b.wt. in drinking water and quercetin was given at a dose level of 40 mg/kg of b.wt. in drinking water. The ultrastructure of BP-treated mice revealed disruptions in cellular integrity together with nuclear deformation and premature mitochondrial aging. Notably, supplementation with phytochemicals individually resulted in improvement of the ultra-histoarchitecture of BP-treated mice although the improvement was much greater with combined supplementation of phytochemicals. Furthermore, BP treatment revealed alterations in lung histoarchitecture, which, however, were improved appreciably following combined supplementation with curcumin and quercetin. The results of the present study show that, combined supplementation with curcumin and quercetin effectively preserved the histoarchitecture as well as ultra-histoarchitecture during BP-induced lung carcinogenesis in mice.

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Section: Discussionmentioning

confidence: 92%

Ultrastructural changes during lung carcinogenesis-modulation by curcumin and quercetin

Wang

Zhang

et al. 2016

Oncology Letters

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“…Recently, this model was extended to incorporate micronuclei in binucleated cells (BN-MN) (OR 16.72 per unit increase, 95% CI 9.01-31.02) alongside environmental tobacco smoke exposure (OR 1.12, 95% CI 0.47-2.68) and a family history of cancer in two or more first-degree relatives (OR 1.06, 95% CI 0.47-2.43). 21 The average difference in BN-MN between cases and controls in the model's development and validation datasets was 1.78-1.79 units. 21 Assuming the ORs of the model variables closely approximate the RRs and an increase of 1.80 units of BN-MN compared to a never-smoker at average risk is considered, the model considers RRs up to at least 35.73 for never-smokers.…”

Section: Methodsmentioning

confidence: 94%

“…21 The average difference in BN-MN between cases and controls in the model's development and validation datasets was 1.78-1.79 units. 21 Assuming the ORs of the model variables closely approximate the RRs and an increase of 1.80 units of BN-MN compared to a never-smoker at average risk is considered, the model considers RRs up to at least 35.73 for never-smokers.…”

Section: Methodsmentioning

confidence: 94%

“…3, 14-16 A number of risk models incorporate these and other risk factors to identify ever- and never-smokers at elevated levels of risk. 17-21 Recent studies have identified sub-populations within the NLST who were at a higher level of risk for developing lung cancer compared to the average population of the trial. 20, 22, 23 Screening was more effective for these sub-populations, which indicates that screening recommendations based on an individual's risk could lead to more effective screening programs.…”

Section: Introductionmentioning

confidence: 99%

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Should Never-Smokers at Increased Risk for Lung Cancer Be Screened?

Haaf

Koning

2015

Journal of Thoracic Oncology

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Introduction Lung cancer in never-smokers ranks among the ten most common causes of death due to cancer worldwide and in the U.S. However, it is unknown whether never-smokers at elevated risk for developing lung cancer may benefit from lung cancer screening. Methods The MISCAN-Lung microsimulation model was used to assess the effects of lung cancer screening for simulated cohorts of never-smokers at different levels of relative risk (RR) for lung cancer compared to never-smokers at average risk. The benefits and harms of screening were estimated for each cohort and compared to those of a cohort of ever-smokers eligible for lung cancer screening according to the United States Preventive Services Task Force (USPSTF) criteria. Results The relative lung cancer mortality reduction in never-smokers was higher than the USPSTF eligible cohort (37% compared to 32%). However, the number of life-years gained per lung cancer death averted was lower (10.4 compared to 11.9) and the proportion of overdiagnosed cancers was higher (9.6% compared to 8.4%) for never-smokers compared to the USPSTF eligible cohort, as never-smokers are diagnosed at a later age. The estimated number of screens per lung cancer death averted ranged from 6,162 for never-smokers at average risk to 151 for never-smokers with a RR of 35, compared to 353 for the USPSTF eligible cohort. Conclusions Never-smokers with RRs of 15-35 have similar to better trade-offs between benefits and harms compared to ever-smokers recommended for lung cancer screening by the USPSTF guidelines. For most never-smokers, lung cancer screening is not beneficial.

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“…Examining a subset of cases and controls from their original study, Spitz et al found their models for former and current smokers performed better when adding two host DNA repair capacity markers (AUCs, 0.68 and 0.70) [33]. El-Zein et al [34] likewise extended the original smoking-stratified Spitz models by adding a cytokinesis-blocked micronucleus assay endpoint, which substantially improved prediction in a small external validation sample (AUC, from 0.61 to 0.92). Due to the case-control design, however, it is not entirely clear whether these markers reflect underlying causes or effects of lung cancer.…”

Section: Predicting Lung Cancer Risk Prior To Screening Initiationmentioning

confidence: 99%

Applying Risk Prediction Models to Optimize Lung Cancer Screening: Current Knowledge, Challenges, and Future Directions

et al. 2017

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Structured Abstract Purpose of review Risk prediction models may be useful for facilitating effective and high-quality decision-making at critical steps in the lung cancer screening process. This review provides a current overview of published lung cancer risk prediction models and their applications to lung cancer screening and highlights both challenges and strategies for improving their predictive performance and use in clinical practice. Recent findings Since the 2011 publication of the National Lung Screening Trial results, numerous prediction models have been proposed to estimate the probability of developing or dying from lung cancer or the probability that a pulmonary nodule is malignant. Respective models appear to exhibit high discriminatory accuracy in identifying individuals at highest risk of lung cancer or differentiating malignant from benign pulmonary nodules. However, validation and critical comparison of the performance of these models in independent populations are limited. Little is also known about the extent to which risk prediction models are being applied in clinical practice and influencing decision-making processes and outcomes related to lung cancer screening. Summary Current evidence is insufficient to determine which lung cancer risk prediction models are most clinically useful and how to best implement their use to optimize screening effectiveness and quality. To address these knowledge gaps, future research should be directed toward validating and enhancing existing risk prediction models for lung cancer and evaluating the application of model-based risk calculators and its corresponding impact on screening processes and outcomes.

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The Cytokinesis-Blocked Micronucleus Assay as a Strong Predictor of Lung Cancer: Extension of a Lung Cancer Risk Prediction Model

Cited by 38 publications

References 39 publications

Ultrastructural changes during lung carcinogenesis-modulation by curcumin and quercetin

Ultrastructural changes during lung carcinogenesis-modulation by curcumin and quercetin

Should Never-Smokers at Increased Risk for Lung Cancer Be Screened?

Applying Risk Prediction Models to Optimize Lung Cancer Screening: Current Knowledge, Challenges, and Future Directions

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