Somatic-cell mutations as a possible predictor of cancer risk.

The somatic-mutation theory of carcinogenesis has received strong scientific support from results of recent studies on tumor-suppressor genes. We anticipated that people among the high risk for cancer group, either through exposure to various ionizing radiations or by virtue of unique genotypes, would also manifest increased frequencies of somatic mutation. This report presents the results of two somatic-mutation assays--at the erythrocyte glycophorin A (GPA) and lymphocyte T-cell receptor (TCR) genes--in various groups at high risk for cancer development, including atomic-bomb survivors, patients with various cancers, patients administered Thorotrast, and patients with genetic disorders that make them cancer prone. Although neither the GPA-mutation nor the TCR-mutation assay detects gene mutations directly related to carcinogenesis, increased mutation frequencies were detected by both assays in many individuals among the high-risk groups and among cancer patients. We have continued to follow up those individuals who show values of about three times higher than those of the control group. Thus, these assays may prove useful for identifying high-risk cancer groups and for estimating the effects of mutagens. Such information would constitute a valuable data base for epidemiological studies.