title: Factors associated with human small aggressive non small cell lung cancer.
abstract: BACKGROUND
  Some non-small cell lung cancers (NSCLC) progress to distant lymph nodes or metastasize while relatively small. Such small aggressive NSCLCs (SA-NSCLC) are no longer resectable with curative intent, carry a grave prognosis, and may involve unique biological pathways. This is a study of factors associated with SA-NSCLC.
  
  
  METHODS
  A nested case-case study was embedded in the National Cancer Institute's Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. SA-NSCLC cases had stage T1, N3, and/or M1 NSCLC (n = 48) and non-SA-NSCLC cases had T2 to T3, N0 to N2, and M0 NSCLC (n = 329). Associations were assessed by multiple logistic regression.
  
  
  RESULTS
  SA-NSCLCs were associated with younger age at diagnosis [odds ratio (OR)(>or=65 versus <65), 0.44; 95% confidence interval (95% CI), 0.22-0.88], female gender, family history of lung cancer, and the interaction gender*family history of lung cancer and were inversely associated with ibuprofen use (OR(yes versus no), 0.29; 95% CI, 0.11-0.76). The ORs for associating gender (women versus men) with SA-NSCLC in those with and without a family history of lung cancer were 11.76 (95% CI, 2.00-69.22) and 1.86 (95% CI, 0.88-3.96), respectively. These associations held adjusted for histology and time from screening to diagnosis and when alternative controls were assessed.
  
  
  CONCLUSIONS
  SA-NSCLC was associated with female gender, especially in those with a family history of lung cancer. If these exploratory findings, which are subject to bias, are validated as causal, elucidation of the genetic and female factors involved may improve understanding of cancer progression and lead to preventions and therapies. Ibuprofen may inhibit lung cancer progression.
authors.affiliation: Department of Community Health Sciences, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario, Canada L2S 3A1. martin.tammemagi@brocku.ca
authors.forename: C Martin
authors.initials: CM
authors.lastname: Tammemagi
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Freedman
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Church
authors.forename: Martin M
authors.initials: MM
authors.lastname: Oken
authors.forename: William G
authors.initials: WG
authors.lastname: Hocking
authors.forename: Paul A
authors.initials: PA
authors.lastname: Kvale
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Riley
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Ragard
authors.forename: Philip C
authors.initials: PC
authors.lastname: Prorok
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009367:Neoplasm Staging; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen