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Insight into development of lung cancer

August 18, 2018
Dartmouth-Hitchcock Medical Center
Lung cancer results from effects of smoking along with multiple genetic components. A new study identifies two main pathways for the role of chromosome 15q25.1 -- a leader in increasing susceptibility to lung cancer -- in modifying disease risk. One pathway is implicated in nicotine dependence. The other plays a part in biological processes such as nutrient transfer and immune system function. The findings increase our understanding of lung cancer cause and development.


Lung cancer is the leading cause of preventable cancer death. A disease of complex origin, lung cancer is usually considered to result from effects of smoking and from multiple genetic variants. One of these genetic components, a chromosome named 15q25.1, has been previously identified as a leading influencer of susceptibility to lung cancer, smoking behavior, and nicotine addiction. However, no previous study has investigated the mechanisms of this lead agent, or documented the susceptibility pathways that allow this chromosome to modify development of disease.

A research team led by Xuemie Ji, MD, PhD, Research Associate in Department of Biomedical Data Science at Dartmouth's Geisel School of Medicine, helped solve this central problem. The team identified two main pathways involving the mechanism by which the chromosome 15q25.1 locus influences lung cancer risk. The first pathway is an interaction pathway in the nervous system that is implicated in nicotine dependence. The other pathway can control key components in many biological processes, such as transport of nutrients and ions, and the human immune system.

The results have been newly published in Nature Communications. "Our findings in pathways uncover insights into the mechanism of lung cancer etiology and development, which will potentially shorten the interval between increasing biological knowledge and translation to patient care," says Ji. "Blocking genes downstream or in parallel pathways might provide a strategy to treat such cancer."

The study used two independent cohorts of 42,901 individuals with a genome-wide set of genetic variants, as well as an expression dataset with lung tissue from 409 lung cancer patients to validate findings. Two different methods were used to analyze data, and confirm that the findings are reliable and can be repeated with different methods. "To our knowledge, this is the first study to explore the pathogenic pathways related to the mechanisms of chromosome 15q25.1 and the first to use a novel analysis approach to analyze data and to validate the findings," says Ji. "The ability to block the damaging genetic variants downstream or in parallel pathways might improve lung cancer prognosis and survival, and therefore provide alternative strategies to treat such cancer."

The team is working to identify more mechanisms contributing to the increased risk of lung cancer. They aim to provide more explanation for the large unexplainable division of lung cancer occurrences.


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Materials provided by Dartmouth-Hitchcock Medical Center. Note: Content may be edited for style and length.

Journal Reference:

  1. Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella de Biasi, Younghun Han, Olga Gorlova, Rayjean J. Hung, Xifeng Wu, James McKay, Xuchen Zong, Robert Carreras-Torres, David C. Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E. Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, Chu Chen, M. Dawn Teare, John K. Field, Lambertus A. Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B. Schabath, Angeline S. Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier A. Bertazzi, Angela C. Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S. Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H. F. M. van der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P. A. Davies, Michael W. Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C. Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer Doherty, Gary E. Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M. Arnold, Eric B. Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M. Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J. Duell, Lesley M. Butler, Woon-Puay Koh, Yu-Tang Gao, Richard Houlston, John McLaughlin, Victoria Stevens, David C. Nickle, Ma’en Obeidat, Wim Timens, Bin Zhu, Lei Song, María Soler Artigas, Martin D. Tobin, Louise V. Wain, Fangyi Gu, Jinyoung Byun, Ahsan Kamal, Dakai Zhu, Rachel F. Tyndale, Wei-Qi Wei, Stephen Chanock, Paul Brennan, Christopher I. Amos. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-05074-y

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Dartmouth-Hitchcock Medical Center. "Insight into development of lung cancer." ScienceDaily. ScienceDaily, 18 August 2018. <>.
Dartmouth-Hitchcock Medical Center. (2018, August 18). Insight into development of lung cancer. ScienceDaily. Retrieved September 29, 2023 from
Dartmouth-Hitchcock Medical Center. "Insight into development of lung cancer." ScienceDaily. (accessed September 29, 2023).

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