Genetic Susceptibility to Lung Cancer as Determined by Lymphocytic Chromosome Analysis1

Chromosomal anomalies were analyzed in the lymphocyte cultures among 96 untreated lung cancer patients and 74 clinically normal comparison subjects. The analysis revealed that >15% of the lung cancer patients showed structural or numerical rearrangements in chromosomes 1, 3, 5, 7, 9, 12, 14, and 21. A case control comparison showed that these aberrations were significantly higher in chromosome 7 [odds ratio (OR) = 2.32; 95% confldence interval (CI), 1.14 and 4.82], chromosome 9 (OR = 2.61; 95% CI, 1.27 and 5.48), chromosome 12 (OR = 4.10; 95% CI, 1.40 and 14.54), and chromosome 21 (OR = 7.75; 95% CI, 1.73 and 70.80) of the patients than in the Controls. However, only chromosome 9 (OR = 3.57; 95% CI, 1.33 and 9.46) and chromosome 21 (OR = 6.94; 95% CI, 3.15 and 9.98) retained significance after stratifying on smoking status. Among the lung cancer patients, the breakpoints cluster in specific regions of some of these chromosomes. These regions are Ipl3-q21, 3p21-ql3, 7pl2-ql2, 7q22, 7q32, 9pl3-ql3, 12pl3, 14qll, and 14q32. The distribution of lung cancer patients, according to histological types, showed that aberrations in chromosomes 1, 7, and 9 dominated the scenario of chromosomal changes in non-small cell lung carcinomas. Thus, the data on lymphocytic chromosomal rearrangements in lung cancer patients not only indicate the importance of specific genetic changes in the etiology of lung cancer but also emphasizes the putative role of such analysis in determining primary genetic abnormalities in the large heterogeneous group of lung cancers.