An Integrated Approach to Understand, Prevent and Cure Lung Cancer in Never Smokers

The research team in the Epidemiology and Genetics of Lung Cancer Research Program at Mayo Clinic has carefully designed several projects in multiple directions to further understand genomic and environmental factors that significantly impact the development, progression and prognosis of lung cancer in never smokers.

Never smokers in the context of lung cancer are commonly defined as people who have smoked fewer than 100 cigarettes.

More than half of lung cancer cases occur in people who have never smoked or who are former smokers, with women disproportionally affected among those who have never smoked.

Physicians and scientists have long recognized that lung cancer in never smokers is a different disease from lung cancer in people who are smokers.

In this project, An Integrated Approach to Understand, Prevent and Cure Lung Cancer in Never Smokers, the research team is identifying the effects of secondhand smoking exposure in both childhood and adulthood and genomic alterations at various levels to see if there may be direct or indirect therapeutic targets.

Related publications

  • Sun Z, Wang L, Eckloff BW, Deng B, Wang Y, Wampfler JA, Jang J, Wieben ED, Jen J, You M, Yang P. Conserved recurrent gene mutations correlate with pathway deregulation and clinical outcomes of lung adenocarcinoma in never-smokers. BMC Med Genomics. 2014.
  • Deng B, Molina J, Aubry MC, Sun Z, Wang L, Eckloff BW, Vasmatzis G, You M,Wieben ED, Jen J, Wigle DA, Yang P. Clinical biomarkers of pulmonary carcinoid tumors in never smokers via profiling miRNA and target mRNA. Cell Biosci. 2014;4:35.
  • Ryan BM, Wang Y, Jen J, Yi ES, Olivo-Marston S, Yang P, Harris CC. Evidence that the lung Adenocarcinoma EML4-ALK fusion gene is not caused by exposure to secondhand tobacco smoke during childhood. Cancer Epidemiol Biomarkers Prev. 2014;23(7):1432-4.
  • Boland JM, Wampfler JA, Jang JS, Wang X, Erickson-Johnson MR, Oliveira AM, Yang P, Jen J, Yi ES. Pulmonary adenocarcinoma with signet ring cell features: a comprehensive study from 3 distinct patient cohorts. Am J Surg Pathol. 2014;38(12):1681-8.
  • Spitz MR, Gorlov IP, Amos CI, Dong Q, Chen W, Etzel CJ, Gorlova OY, Chang DW, Pu X, Zhang D, Wang L, Cunningham JM, Yang P, Wu X. Variants in inflammation genes are implicated in risk of lung cancer in never smokers exposed to second-hand smoke. Cancer Discov. 2011;1(5):420-9.
  • Hildebrandt MA, Hsiung CA, Yang P. Genome-wide association study of genetic predictors of overall survival for non-small cell lung cancer in never smokers. Cancer Res. 2013;73(13):4028-38.
  • Boland JM, Jang JS, Li J, Lee AM, Wampfler JA, Erickson-Johnson MR, Soares I, Yang P, Jen J, Oliveira AM, Yi ES. MET and EGFR mutations identified in ALK-rearranged pulmonary adenocarcinoma: molecular analysis of 25 ALK-positive cases. J Thorac Oncol. 2013;8(5):574-81.
  • Pu X, Ye Y, Spitz MR, Wang L, Gu J, Lippman SM, Hildebrandt MA, Hong WK, Minna JD, Roth JA, Yang P, Wu X. Predictors of survival in never-smokers with non-small cell lung cancer: a large-scale, two-phase genetic study. Clin Cancer Res. 2012;18(21):5983-91.
  • Yang P. Lung cancer in never smokers. Semin Respir Crit Care Med. 2011;32(1):10-21. Review. PMID: 21500120; PMCID: PMC3404817.
  • Jang JS, Jeon HS, Sun Z, Aubry MC, Tang H, Park CH, Rakhshan F, Schultz DA, Kolbert CP, Lupu R, Park JY, Harris CC, Yang P, Jen J. Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from never smokers. Clin Cancer Res. 2012;18(13):3658-67. PMID: 22573352; PMCID: PMC3616503.
  • Yang P, Kulig K, Boland JM, Erickson-Johnson MR, Oliveira AM, Wampfler J, Jatoi A, Deschamps C, Marks R, Fortner C, Stoddard S, Nichols F, Molina J, Aubry MC, Tang H, Yi ES. Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma. J Thorac Oncol. 2012;7(1):90-7. PMID: 22134072; PMCID:PMC3931519.
  • Li Y, Sheu CC, Ye Y, de Andrade M, Wang L, Chang SC, Aubry MC, Aadre JA, Allen MS, Chen F, Cunningham JM, Deschamps C, Jiang R, Lin J, Marks RS, Pankratz VS, Su L, Li Y, Sun Z, Tang H, Vasmatzis G, Harris CC, Spitz MR, Jen J, Wang R, Zhang ZF, Christiani DC, Wu X, Yang P. Genetic variants and risk of lung cancer in never smokers: a GWAS. Lancet Oncol. 2010;11(4):321-30.
  • Olivo-Marston SE, Yang P, Mechanic LE, Bowman ED, Pine SR, Loffredo CA, Alberg AJ, Caporaso, N, Shields PG, Chanock S, Wu Y, Jiang R, Cunningham J, Jen J, Harris CC. Childhood exposure to secondhand smoke and functional mannose binding lectin polymorphisms are associated with increased lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2009;18(12):3375-83.
  • de Andrade M, Ebbert JO, Wampfler JA, Miller DL, Marks RS, Croghan GA, Jatoi A, Finke EE, Sellers TA, Yang P. Environmental tobacco smoke exposure in women with lung cancer. Lung Cancer. 2004;43(2):127-34.