PMID- 20332298 OWN - NLM STAT- MEDLINE DCOM- 20100625 LR - 20211020 IS - 1940-6215 (Electronic) IS - 1940-6207 (Print) IS - 1940-6215 (Linking) VI - 3 IP - 4 DP - 2010 Apr TI - The detection of chromosomal aneusomy by fluorescence in situ hybridization in sputum predicts lung cancer incidence. PG - 447-53 LID - 10.1158/1940-6207.CAPR-09-0165 [doi] AB - Lung cancer usually is disseminated (advanced) and has a poor prognosis at diagnosis. Current and former smokers are at a high risk for lung cancer and are candidates for prevention and early detection strategies. Sputum is a potential source of biomarkers that might determine either lung cancer risk or the presence of early lung cancer, but no current sputum test is sufficiently sensitive and specific for effective screening. We used fluorescence in situ hybridization (FISH) to measure chromosomal aneusomy (CA) in sputum samples collected prospectively from 100 incident lung cancer cases and 96 controls (matched on age, gender, and date of collection) nested within an ongoing high-risk cohort. The CA-FISH assay was aimed at four DNA targets: epidermal growth factor receptor, MYC, 5p15, and CEP 6. The sensitivity of a positive CA-FISH assay (abnormal for two or more of the four markers) for lung cancer was substantially higher for samples collected within 18 months (76% sensitivity) than for samples collected more than 18 months (31%) before lung cancer diagnosis. Sensitivity was higher for squamous cell cancers (94%) than for other histologic types (69%). CA-FISH specificity based on samples collected within 18 months before diagnosis was 88%. The adjusted odds ratio (OR) of lung cancer for specimens collected within 18 months before a cancer diagnosis was higher for the CA-FISH assay [OR, 29.9; 95% confidence interval (95% CI), 9.5-94.1] than for previously studied ORs of cytologic atypia (OR, 1.8; 95% CI, 1.3-2.6) and gene promoter methylation (OR, 6.5; 95% CI, 1.2-35.5). Whether CA-FISH is an indicator of extreme risk for incident lung cancer or detects exfoliated cancer cells is unknown. The apparent promise of CA-FISH in sputum for assessing lung cancer risk and/or for lung cancer early detection now needs to be validated in a clinical screening trial. CI - (c) 2010 AACR. FAU - Varella-Garcia, Marileila AU - Varella-Garcia M AD - University of Colorado Denver, 12801 East 17th Avenue, Aurora, CO 80045, USA. Marileila.Garcia@ucdenver.edu FAU - Schulte, Aline P AU - Schulte AP FAU - Wolf, Holly J AU - Wolf HJ FAU - Feser, William J AU - Feser WJ FAU - Zeng, Chan AU - Zeng C FAU - Braudrick, Sarah AU - Braudrick S FAU - Yin, Xiang AU - Yin X FAU - Hirsch, Fred R AU - Hirsch FR FAU - Kennedy, Timothy C AU - Kennedy TC FAU - Keith, Robert L AU - Keith RL FAU - Baron, Anna E AU - Baron AE FAU - Belinsky, Steven A AU - Belinsky SA FAU - Miller, York E AU - Miller YE FAU - Byers, Tim AU - Byers T FAU - Franklin, Wilbur A AU - Franklin WA LA - eng GR - P50CA58184/CA/NCI NIH HHS/United States GR - P50 CA058187/CA/NCI NIH HHS/United States GR - P30 CA046934-22S49003/CA/NCI NIH HHS/United States GR - P50 CA058184/CA/NCI NIH HHS/United States GR - P30 CA046934/CA/NCI NIH HHS/United States GR - P30 CA046934-22S59003/CA/NCI NIH HHS/United States GR - P30 CA046934-209003/CA/NCI NIH HHS/United States GR - P30 CA046934-22S39003/CA/NCI NIH HHS/United States GR - U01-CA85070/CA/NCI NIH HHS/United States GR - P30 CA046934-229003/CA/NCI NIH HHS/United States GR - U01 CA085070/CA/NCI NIH HHS/United States GR - P30-CA46934/CA/NCI NIH HHS/United States GR - P50CA58187/CA/NCI NIH HHS/United States GR - P30 CA046934-219003/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100323 PL - United States TA - Cancer Prev Res (Phila) JT - Cancer prevention research (Philadelphia, Pa.) JID - 101479409 RN - 0 (Biomarkers, Tumor) SB - IM CIN - Cancer Prev Res (Phila). 2010 Apr;3(4):420-3. PMID: 20332300 CIN - Cancer Prev Res (Phila). 2010 Apr;3(4):416-9. PMID: 20332302 MH - Aged MH - Area Under Curve MH - Biomarkers, Tumor/analysis/*genetics MH - Female MH - Humans MH - In Situ Hybridization, Fluorescence/*methods MH - Incidence MH - Lung Neoplasms/*diagnosis/*epidemiology/genetics MH - Male MH - Middle Aged MH - Neoplasm Staging MH - ROC Curve MH - Sensitivity and Specificity MH - Sputum/*cytology PMC - PMC2939746 MID - NIHMS157372 EDAT- 2010/03/25 06:00 MHDA- 2010/06/26 06:00 PMCR- 2011/04/01 CRDT- 2010/03/25 06:00 PHST- 2010/03/25 06:00 [entrez] PHST- 2010/03/25 06:00 [pubmed] PHST- 2010/06/26 06:00 [medline] PHST- 2011/04/01 00:00 [pmc-release] AID - 1940-6207.CAPR-09-0165 [pii] AID - 10.1158/1940-6207.CAPR-09-0165 [doi] PST - ppublish SO - Cancer Prev Res (Phila). 2010 Apr;3(4):447-53. doi: 10.1158/1940-6207.CAPR-09-0165. Epub 2010 Mar 23.