Site-Specific Determinants of Cutaneous Melanoma: A Case–Case Comparison of Patients with Tumors Arising on the Head or Trunk

Abstract

Cutaneous melanomas have been hypothesized to arise through different pathways according to phenotype, body site, and sun exposure. To further test this hypothesis, we explored associations between phenotype and melanoma at different sites using a case-case comparative approach. Melanoma patients (n = 762) aged 18 to 79 years and diagnosed from 2007 to 2010 were ascertained from pathology laboratories in Brisbane, Australia. Patients reported phenotypic information and a dermatologist counted melanocytic nevi and solar keratoses. We compared data for patients with trunk melanoma (n = 541, the reference group), head/neck melanoma (n = 122), or lentigo maligna melanoma (LMM) of the head/neck (n = 69). ORs and 95% confidence intervals were calculated using classical or polytomous logistic regression models. Compared with trunk melanoma patients, those with head/neck melanoma were significantly less likely to have high nevus counts (≥135: OR = 0.27; Ptrend = 0.0004). Associations between category of nevus count and LMM head/neck were weaker and significantly different (≥135: OR = 1.09; Ptrend = 0.69; Phomogeneity = 0.02). Patients with head/neck melanoma were more likely than those with truncal melanoma to have high solar keratosis counts (≥7: OR = 1.78, Ptrend = 0.04). Again, associations with LMM head/neck were weaker, albeit not significantly different (≥7: OR = 1.61; Ptrend = 0.42; Phomogeneity = 0.86). Trunk melanomas are more strongly associated with nevus counts than head/neck melanomas, but are less strongly associated with number of solar keratoses, a marker of chronic sun exposure. These findings underscore the notion that melanomas on the trunk typically arise through a causal pathway associated with nevus propensity, whereas melanomas on the head/neck arise through a pathway associated with cumulative sun exposure.