Towards Lung Cancer Precision Prevention in Chinese Populations

Identification of risk loci and a polygenic risk score for lung cancer in a large-scale prospective cohort study in Chinese populations
22 Jul 2019
Translational research;  Epidemiology/Etiology/Cancer Prevention

Having in mind that genetic factors for lung cancer are not fully identified, especially in Chinese populations, a group of Chinese researchers have shown for the first time that genome-wide association study (GWAS)-derived polygenic risk scores can be effectively used in discriminating subpopulations at high risk of lung cancer, who might benefit from a practically feasible polygenic risk score-based lung cancer screening programme for precision prevention in Chinese populations. The findings are published on 17 July 2019 in The Lancet Respiratory Medicine.

Another article about mortality, morbidity, and risk factors in China and its provinces published on 24 June 2019 in The Lancet, states that public health is a priority for the Chinese government. The Healthy China 2030 plan is the signature Chinese national domestic population health policy that has made population health the ultimate goal of economic development and political reform. Two of the goals are to improve longevity and healthy life expectancy and to increase disease prevention.

Evidence-based decision making for health in China, which is home to a fifth of the global population, is therefore of paramount importance. In the analysis that used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 to help inform decision making and monitor progress on health at the province level, the study authors reported that age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of years of life lost in 2017.

By underlining a magnitude of lung cancer as a health problem in China, we therefore, come back to discovery of risk loci and innovations that might be of relevance for lung cancer prevention strategies.

The authors wrote in the background of study published in The Lancet Respiratory Medicine that genetic variation has an important role in the development of non-small cell lung cancer (NSCLC). But not having a full picture on genetic factors in Chinese populations limits the use of existing polygenic risk scores to identify subpopulations at high risk of lung cancer for prevention.

Therefore, the Chinese investigators performed a study with an aim to identify novel loci associated with NSCLC risk, and generate a polygenic risk score and evaluate its utility and effectiveness in the prediction of lung cancer risk in Chinese populations.

In particular, they newly genotyped 19,546 samples from Chinese patients with NSCLC and controls from the Nanjing Medical University Global Screening Array Project and performed a meta-analysis of GWAS of 27,120 individuals with NSCLC and 27,355 without NSCLC from whom there were 13,327 cases and 13,328 controls of Chinese descent as well as 13,793 cases and 14,027 controls of European descent.

They then built a polygenic risk score for Chinese populations from all reported single-nucleotide polymorphisms that have been reported to be associated with lung cancer risk at genome-wide significance level. They evaluated the utility and effectiveness of the generated polygenic risk score in predicting subpopulations at high-risk of lung cancer in an independent prospective cohort of 95,408 individuals from the China Kadoorie Biobank (CKB) with more than 10 years' follow-up.

The study team identified 19 susceptibility loci to be significantly associated with NSCLC risk at p ≤ 5.0×10−8, including six novel loci. When applied to the CKB cohort, the polygenic risk score of the risk loci successfully predicted lung cancer incident cases in a dose-response manner in participants at a high genetic risk (top 10%) than those at a low genetic risk (bottom 10%); adjusted hazard ratio 1.96, p trend = 2.02×10−9.

The study team observed consistently separated curves of lung cancer events in individuals at low, intermediate, and high genetic risk, respectively, and polygenic risk score was an independent effective risk stratification indicator beyond age and smoking pack-years.

The GWAS study was funded by the National Natural Science Foundation of China, the Priority Academic Programme for the Development of Jiangsu Higher Education Institutions, National Key R&D Programme of China, Science Foundation for Distinguished Young Scholars of Jiangsu, and China's Thousand Talents Programme.

A systematic analysis of mortality, morbidity, and risk factors in China and its provinces was funded by China National Key Research and Development Programme and Bill & Melinda Gates Foundation.

 

References

Dai J, Lv J, Zhu M, et al. Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations. The Lancet Respiratory Medicine; Published online 17 July 2019. DOI:https://doi.org/10.1016/S2213-2600(19)30144-4.

Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet; Published on 24 June 2019. pii: S0140-6736(19)30427-1. doi: 10.1016/S0140-6736(19)30427-1.

Last update: 22 Jul 2019

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