Other Genes Modifying Susceptibility to Inherited and Environmental Neoplastic Disease
The identification of specific genes involved in the multifactorial inheritance of neoplasia may be grouped into a number of different general categories. We have already discussed the involve- ment of genes involved in DNA repair. Three other areas involve gene products of the HLA lo- cus coding for surface membrane antigens involved in immune mechanisms (Chapter 17), proto- oncogenes, and pharmacogenetics. In the former category there is substantial evidence that spe- cific HLA haplotypes (genotypes) are associated with an increased incidence of specific human neoplasms, as reported in sporadic instances. As can be seen from Table 5.10, the greatest risks related to specific HLA antigen haplotypes are associated with leukemias and lymphomas, the
notable exceptions being neoplasms of the kidney and testicle. Since many leukemias and lym- phomas arise from cells of the immune system where HLA haplotypes play a major role in gene expression, the results seen in Table 5.10 might be expected, perhaps in relation to the immuno- biology of the host-tumor relationship (Chapter 19). In another cell surface gene family, the ABO blood groups, a relationship between blood group A and cancer of the stomach was found among black and white patients in the southern United States (Newell et al., 1974).