Association between phenotypic characteristics and melanoma in a large prospective cohort study

Abstract

To delineate causal pathways for melanoma, it is essential to derive unbiased estimates of risk. Extant knowledge derives largely from case-control studies with potential for bias. In a population-based prospective study (QSkin, n=38,854), we assessed melanoma risks associated with pigmentation characteristics and other phenotypes, and explored additive interactions. We fitted Cox proportional hazards models adjusting for other factors to estimate independent effects of each characteristic on melanoma risk. During a mean follow-up of 3.5 years, 642 (1.5%) participants developed melanoma (253 invasive, 389 in situ). The characteristics most strongly associated with invasive melanoma were self-reported nevus density at age 21 ('many' vs. no moles HR 4.91 [2.81-8.55]), inability to tan ('no tan' vs. 'deep tan' HR 3.39 [1.85-6.20]) and red hair color (vs. black HR 3.11 [1.50-6.43]). Notably, propensity to sunburn was not associated with melanoma after adjusting for tanning inability. People with both high nevus density and a history of multiple keratinocyte cancers had significantly higher melanoma risks than those having only one of those traits. We infer that melanoma risk is more strongly related to nevus density and inability to tan than susceptibility to sunburn.