Loss of heterozygosity and the smoking index increase with decrease in differentiation of lung adenocarcinomas: etiologic implications.

To better understand causative relations of smoking to lung adenocarcinomas, the frequency of loss of heterozygosity (LOH) of all autosomal chromosomes was compared among the three grades of histological differentiation with 119 pulmonary adenocarcinomas (AC) and 41 squamous cell carcinomas (SCC), using Southern blotting. The fractional allelic loss (FAL) values, defined as (number of chromosome arms with LOH)/(number of informative arms), and smoking index (a product of number of cigarettes per day and duration in years) for all ACs were 0.19 and 520 whereas those for SCCs were 0.34 and 1,160, respectively. Those for well- (n=33), moderately (n=63) and poorly (n=23) differentiated ACs were 0.100, 0.197, 0.295 and 310, 480, 1,010, respectively. These results showed that less differentiated ACs are more similar to SCC in terms of LOH frequency and smoking.