Genetics of risk factors for melanoma: An adult twin study of nevi and freckles

Background: We sought by use of an adult twin study to investigate the rela tive contribution of genetic and environmental effects on the expression of nevi and freckles, which are known risk factors for melanoma, and to deter mine if age and sun exposure influence the heritability of nevi, Design and Methods: Total nevus and freckle counts were conducted on 127 monozygotic twin pairs and 323 dizygotic twin pairs. Intraclass correlations were calcu lated by use of analysis of variance. Model-fitting analyses were performed to quantify the genetic and environmental components of the variance for n evus and freckle counts.Results: The intraclass correlation for total nevus counts was 83 in monozygotic pairs compared with 51 in dizygotic pairs. Qu antitative genetic analyses showed that the contribution of genetic factors on nevi expression varied according to age. For twins less than 45 years o ld, the additive genetic variance on total nevus count was 36% (95% confide nce interval [Cl] = 0.8%-63%), with 38% (95% CI = 14%-61%) and 26% (95% CI = 16%-42%) of the remaining variance attributed to common environment and u nique environmental effects, respectively. In twins aged 45 years or older, common environmental effects on total nevus count became negligible, with the additive genetic variance increasing to 84% (95% CI = 77%-88%), Body si te was also found to affect the heritability estimates for nevus counts, wi th a statistically significant difference between sun-exposed and sun-prote cted sites. The polychoric correlation (i.e., the correlation in liability within twins for more than two categories) for total freckle counts was .91 in monozygotic twin pairs compared with .54 in dizygotic twin pairs. Addit ive genetic effects explained 91% (95% CI = 86%-94%) of the variance in fre ckle counts. Conclusion: The contribution of genetic factors on the varianc e for total nevus counts increased with age, and sun exposure appears to in fluence the expression of nevi, The results of this study highlight the nee d to take into account the age and site of nevus counts for future genetic linkage or association studies in the search for new melanoma genes.