Distribution and rearrangements of alleles of c-Ha-ras-1 protooncogene and their correlation with the development of lung, ovarian and thyroid cancers.

The protooncogene c-Ha-ras-1 locus in 84 cancer patients was examined for allelic restriction fragment length polymorphism. The distribution of four common c-Ha-ras-1 alleles (a1, a2, a3 and a4) in lung, ovarian and thyroid cancer patients was analyzed. In approximately half (8 out of 15) of lung and ovarian carcinomas possessing the a4 allele, alterations of the c-Ha-ras-1 locus (deletion of allele with the shorter fragment length, amplification of a4 allele, change of allele fragment length) were detected as compared to 2 cases of rearrangement out of 40 tumors lacking the a4 allele. An increased a4 allele frequency was found in individuals with lung and ovarian tumors as compared to controls presented in literary data and thyroid cancer patients. On the other hand, homozygosity for the a2 locus resulting from the deletion of another allele, and increased a2 allele frequency in thyroid cancer patients were observed. Thus the a4 and a2 alleles of c-Ha-ras-1 may perhaps be viewed as genetic markers of predisposition to lung, ovarian and thyroid cancer, respectively, in combination with other clinical parameters.