The Ah Locus. A Gene with Possible Importance in Cancer Predictability

Abstract

The Ah locus represents a complex "cluster" of genes controlling the induction of numerous drug-metabolizing enzyme "activities". Regulation involves a cytosolic receptor similar in many ways to the steroid receptors. Allelic differences at the Ah locus have been shown to be associated in the mouse with increased individual risk for cancer, mutation, drug toxicity, and birth defects. Aryl hydrocarbon (benzo[a]pyrene) hydroxylase (EC 1.14.14.2) (AHH) is an inducible drug-metabolizing enzyme activity which reflects allelic differences at the Ah locus. The exists sufficient evidence that heritable variation of the Ah locus occurs in man. Growing evidence indicates that persons with higher AHH inducibility in their cultured mitogen-activated lymphocytes may have a statistically significantly increased risk for certain cancers. Experimental difficulties in the day-to-day variability of the AHH assay with cultured lymphocytes or monocytes, however, make it impossible at this time to be certain of whether this induction process is controlled principally by a single gene. It also remains to be determined at the present time whether this genotype can be used as a biochemical marker in the individual patient for predicting increased susceptibility to certain types of environmentally caused cancers or toxicity in man.