In collaboration with researchers at the Mayo Clinic, we successfully analyzed paired lung adenocarcinomas and adjacent non-tumor tissues from 60 patients who were less than 50, older than 79, or between 57-72 years of age at the time of diagnosis for the presence of LOH in five commonly affected chromosome arms including 3p, 3q, 9p, 17p, and 19p. The rate of LOH at each chromosomal arm was compared with clinico-pathological and epidemiological features of the patients. Our result indicated that patients having lung cancers before the age of 50 were more likely to be females (14/19, 74%) and current smokers (37%, and p < 0.05). Furthermore, loss of chromosome 3p in the tumors was highly associated with young age of onset patients present in 68% (13/19) of those younger than 50 compared to 30% (6/20) for those aged 80 or older (Odds Ratio = 3.35, C.I., 1.24, 9.04; p = 0.02). After adjusting for known risk factors, the odds ratio of chromosome 3p loss and early age increased to 5.62 (C.I., = 1.85, 17.09; p<0.01). Fine genetic mapping pinpointed a < 2 Mb fragment containing roughly 50 genes at chromosome 3p21.2 as the regions most strongly associated with patients who had lung cancers younger than age 50. Our data is the first to provide direct evidence linking lung cancer susceptibility in extreme-age populations to a specific genetic alteration in the human genome.
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