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Quantifying Substantial Carcinogenesis of Genetic and Environmental Factors from Measurement Error in the Number of Stem Cell Divisions

BMC Cancer(2022)SCI 2区SCI 3区

Cheeloo College of Medicine | Shandong Health Care Industry Association | Shandong Center for Disease Control and Prevention | Shandong Provincial Big Data Center | Qilu Hospital

Cited 1|Views50
Abstract
BACKGROUND:The relative contributions of genetic and environmental factors versus unavoidable stochastic risk factors to the variation in cancer risk among tissues have become a widely-discussed topic. Some claim that the stochastic effects of DNA replication are mainly responsible, others believe that cancer risk is heavily affected by environmental and hereditary factors. Some of these studies made evidence from the correlation analysis between the lifetime number of stem cell divisions within each tissue and tissue-specific lifetime cancer risk. However, they did not consider the measurement error in the estimated number of stem cell divisions, which is caused by the exposure to different levels of genetic and environmental factors. This will obscure the authentic contribution of environmental or inherited factors.METHODS:In this study, we proposed two distinct modeling strategies, which integrate the measurement error model with the prevailing model of carcinogenesis to quantitatively evaluate the contribution of hereditary and environmental factors to cancer development. Then, we applied the proposed strategies to cancer data from 423 registries in 68 different countries (global-wide), 125 registries across China (national-wide of China), and 139 counties in Shandong province (Shandong provincial, China), respectively.RESULTS:The results suggest that the contribution of genetic and environmental factors is at least 92% to the variation in cancer risk among 17 tissues. Moreover, mutations occurring in progenitor cells and differentiated cells are less likely to be accumulated enough for cancer to occur, and the carcinogenesis is more likely to originate from stem cells. Except for medulloblastoma, the contribution of genetic and environmental factors to the risk of other 16 organ-specific cancers are all more than 60%.CONCLUSIONS:This work provides additional evidence that genetic and environmental factors play leading roles in cancer development. Therefore, the identification of modifiable environmental and hereditary risk factors for each cancer is highly recommended, and primary prevention in early life-course should be the major focus of cancer prevention.
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Cancer prevention,Environment,Stem cell division,Measurement error,Epidemiology
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要点】:该论文通过整合测量误差模型和癌症发生主流模型,评估遗传和环境因素对癌症发展的贡献,发现遗传和环境因素在17种组织癌症风险变异中的贡献至少为92%。

方法】:研究提出了两种不同的建模策略,将测量误差模型与癌症发生的主流模型相结合,以定量评估遗传和环境因素对癌症发展的贡献。

实验】:研究应用了所提出的策略到全球68个国家423个登记处、中国125个登记处以及中国山东省139个县的数据上。结果显示,除了髓母细胞瘤外,遗传和环境因素对其他16种器官特异性癌症的风险贡献都超过60%。