High Frequency of Rare Alleles of the Human c-Ha-ras-1 Proto-oncogene in Breast Cancer Patients2

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Abstract
The c-Ha-ras-1 locus in 104 breast cancer patients and 56 unaffected individuals was examined for allelic restriction fragment-length polymorphism. Four common and 16 rare alleles were detected in the combined populations. The distribution of common and rare alleles differed significantly between the two populations. The common restriction fragments represented 91% of the allele pool in the unaffected population. In breast cancer patients, these common alleles represented only 59% of the allele pool (P<.001). More specifically, the frequency of two of the common fragments, the 6.5- and 8.0-kilobase alleles, was significantly diminished in the breast cancer population (P<.001 and P<.02, respectively). The frequency of rare c-Ha-ras-1 alleles and hence genotypes composed of two rare alleles was increased in the breast cancer population (P<.001). One of the rare alleles had a significant (P<.05) association with these breast cancer patients. These results suggest that genotype analysis of the c-Ha-ras-1 locus, in combination with other clinical parameters, may be of prognostic value in assessing the potential for cancer.