Background: According to the Knudson two-mutational-event theory, two mutations at a genetic locus may be required for the development of some cancers. Persons who have inherited a defect in one chromosome and therefore require only one more mutation for cancer development are at a higher risk of manifesting cancer at a younger age than persons without an inherited mutation, who need two acquired "hits." This difference allows one to distinguish familial and sporadic types of the same malignancy by evaluating age of disease onset.
Methods: To study the role of inheritance in the etiology of familial cutaneous melanoma, characteristics of patients with familial versus nonfamilial melanoma were analyzed according to the Knudson two-mutational-event model.
Results: The familial versus nonfamilial graphs, based on age of diagnosis, did not support this model. However, there was a statistically significant earlier age of diagnosis for patients with familial melanoma. Melanoma thickness was less (i.e., earlier cancer at possibly younger age) for patients with a positive versus a negative family history. Conversely, linear regression, after adjusting for tumor thickness, showed that patients with hereditary melanoma still manifested earlier ages of diagnosis of melanoma compared with sporadic patients.
Conclusions: Genetic patterns other than the two-step model, additional family-related factors, patient-physician sensitization due to a family history, or a combination of these factors might explain this age difference. More complex multistep modeling of the data may be helpful in better characterizing the genetic patterns of cutaneous melanoma.