A genetic analysis of melanoma--polygenic inheritance as a threshold trait

A total of 214 melanoma patients and 193 age- and sex-matched controls, interviewed at the Roswell Park Memorial Institute during the years 1974--1978, provided information regarding 1134 and 1043 New York State first order relatives (parents, offspring and siblings). The vital information provided was checked against the records of the New York State Tumor Registry to find cases of melanoma among relatives. Five cases of melanoma were found among the 1027 New York State relatives of melanoma index cases alive during the period 1949--1978, inclusive. No cases of melanoma were found among New York State relatives of controls. The expected number of melanomas among a cohort of relatives of identical sex and age composition for the interval was 0.625 cases, giving a ratio of observed to expected of 8.0. A similar analysis, restricted to parent-offspring pairs, yielded a ratio of observed to expected of 12.7. A search for additional melanoma cases among second degree relatives of familial index cases yielded no further affected relatives. The incidence of melanoma among relatives of melanoma cases and in a comparable general population were used to estimate the heritability of liability to melanoma as a polygenic trait. A heritability estimate of 0.49 was obtained, using parent-offspring data, indicating that nearly half of the variability in liability to melanoma in this population may be attributed to the additive action of many genes, each with small effect. Pending the replication of these findings, the 12-fold increase in incidence of melanoma among parents and offspring of melanoma cases suggests the importance of counseling and surveillance of relatives of affected individuals by the clinician.