Runs of homozygosity associate with decreased risks of lung cancer in never-smoking East Asian females

Chen, Yi-Xiao; Guo, Yan; Dong, Shan-Shan; Chen, Xiao-Feng; Chen, Jia-Bin; Zhang, Yu-Jie; Yao, Shi; Thynn, Hlaing Nwe; Zhi, Liqiang; Yang, Tie-Lin

doi:10.7150/jca.22855

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J Cancer 2018; 9(21):3858-3866. doi:10.7150/jca.22855 This issue Cite

Research Paper

Runs of homozygosity associate with decreased risks of lung cancer in never-smoking East Asian females

Yi-Xiao Chen^1,2, Yan Guo², Shan-Shan Dong², Xiao-Feng Chen², Jia-Bin Chen², Yu-Jie Zhang², Shi Yao², Hlaing Nwe Thynn², Liqiang Zhi^1✉, Tie-Lin Yang^1,2✉

1. Department of Joint Surgery, Honghui Hospital; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an, P. R. China
2. Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710049, P. R. China

Citation:

Chen YX, Guo Y, Dong SS, Chen XF, Chen JB, Zhang YJ, Yao S, Thynn HN, Zhi L, Yang TL. Runs of homozygosity associate with decreased risks of lung cancer in never-smoking East Asian females. J Cancer 2018; 9(21):3858-3866. doi:10.7150/jca.22855. https://www.jcancer.org/v09p3858.htm

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Abstract

Although genome-wide association studies (GWASs) have identified some risk single-nucleotide polymorphisms in East Asian never-smoking females, the unexplained missing heritability is still required to be investigated. Runs of homozygosity (ROHs) are thought to be a type of genetic variation acting on human complex traits and diseases. We detected ROHs in 8,881 East Asian never-smoking women. The summed ROHs were used to fit a logistic regression model which noteworthily revealed a significant association between ROHs and the decreased risk of lung cancer (P < 0.05). We identified 4 common ROHs regions located at 2p22.1, which were significantly associated with decreased risk of lung cancer (P = 2.00 × 10^-4 - 1.35 × 10^-4). Functional annotation was conducted to investigate the regulatory function of ROHs. The common ROHs were overlapped with potential regulatory elements, such as active epigenome elements and chromatin states in lung-derived cell lines. SOS1 and ARHGEF33 were significantly up-regulated as the putative target genes of the identified ROHs in lung cancer samples according to the analysis of differently expressed genes. Our results suggest that ROHs could act as recessive contributing factors and regulatory elements to influence the risk of lung cancer in never-smoking East Asian females.

Keywords: lung cancer, runs of homozygosity, GWASs, genetic risk factors, regulatory elements

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APA

Chen, Y.X., Guo, Y., Dong, S.S., Chen, X.F., Chen, J.B., Zhang, Y.J., Yao, S., Thynn, H.N., Zhi, L., Yang, T.L. (2018). Runs of homozygosity associate with decreased risks of lung cancer in never-smoking East Asian females. Journal of Cancer, 9(21), 3858-3866. https://doi.org/10.7150/jca.22855.

ACS

Chen, Y.X.; Guo, Y.; Dong, S.S.; Chen, X.F.; Chen, J.B.; Zhang, Y.J.; Yao, S.; Thynn, H.N.; Zhi, L.; Yang, T.L. Runs of homozygosity associate with decreased risks of lung cancer in never-smoking East Asian females. J. Cancer 2018, 9 (21), 3858-3866. DOI: 10.7150/jca.22855.

NLM

CSE

Chen YX, Guo Y, Dong SS, Chen XF, Chen JB, Zhang YJ, Yao S, Thynn HN, Zhi L, Yang TL. 2018. Runs of homozygosity associate with decreased risks of lung cancer in never-smoking East Asian females. J Cancer. 9(21):3858-3866.

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