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- Title
Whole-exome sequencing reveals genetic variability among lung cancer cases subphenotyped for emphysema.
- Authors
Lusk, Christine M.; Wenzlaff, Angela S.; Dyson, Greg; Purrington, Kristen S.; Watza, Donovan; Land, Susan; Soubani, Ayman O.; Gadgeel, Shirish M.; Schwartz, Ann G.
- Abstract
Lung cancer continues to be a major public health challenge in the United States despite efforts to decrease the prevalence of smoking; outcomes are especially poor for African-American patients compared to other races/ethnicities. Chronic obstructive pulmonary disease (COPD) co-occurs with lung cancer frequently, but not always, suggesting both shared and distinct risk factors for these two diseases. To identify germline genetic variation that distinguishes between lung cancer in the presence and absence of emphysema, we performed whole-exome sequencing on 46 African-American lung cancer cases (23 with and 23 without emphysema frequency matched on age, sex, histology and pack years). Using conditional logistic regression, we found 6305 variants (of 168 150 varying sites) significantly associated with lung cancer subphenotype (P = 0.05). Next, we validated 10 of these variants in an independent set of 612 lung cancer cases (267 with emphysema and 345 without emphysema) from the same population of inference as the sequenced cases. We found one variant that was significantly associated with lung cancer subphenotype in the validation sample. These findings contribute to teasing apart shared genetic factors from independent genetic factors for lung cancer and COPD.
- Subjects
UNITED States; LUNG cancer &; genetics; EXOMES; PUBLIC health; PHYSIOLOGICAL effects of tobacco; DISEASES in African Americans; PULMONARY emphysema; NUCLEOTIDE sequencing; LOGISTIC regression analysis
- Publication
Carcinogenesis, 2016, Vol 37, Issue 2, p139
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgv248