Heritability and gene-environment interactions for melanocytic nevus density examined in a UK adolescent twin study

Risk factors for melanoma include environmental (particularly ultraviolet e xposure) and genetic factors. In rare families, susceptibility to melanoma is determined by high penetrance mutations in the genes CDKN2A or CDK4, wit h more common, less penetrant genes also postulated. A further, potent risk factor for melanoma is the presence of large numbers of melanocytic nevi s o that genes controlling nevus phenotype could be such melanoma susceptibil ity genes. A large Australian study involving twins aged 12 y of predominan tly U.K. ancestry showed strong evidence for genetic influence on nevus num ber and density. We carried out essentially the same study in the U.K. to g ain insight into gene-environment interactions for nevi. One hundred and th ree monozygous (MZ) and 118 dizygous (DZ) twin pairs aged 10-18 y were exam ined in Yorkshire and Surrey, U.K. Nevus counts were, on average, higher in boys (mean = 98.6) than girls (83.8) (p = 0.009) and higher in Australia ( 110.4) than in the U.K. (79.2, adjusted to age 12 y, p < 0.0001), and nevus densities were higher on sun-exposed sites (92 per m(2)) than sun-protecte d sites (58 per m(2)) (p < 0.0001). Correlations in sex and age adjusted ne vus density were higher in MZ pairs (0.94, 95% CI 0.92-0.96) than in DZ pai rs (0.61, 95%CI 0.49-0.72), were notably similar to those of the Australian study (MZ = 0.94, DZ = 0.60), and were consistent with high heritability ( 65% in the U.K., 68% in Australia). We conclude that emergence of nevi in a dolescents is under strong genetic control, whereas environmental exposures affect the mean number of nevi.