Keratinocyte Carcinoma as a Marker of a High Cancer-Risk Phenotype

Keratinocyte carcinoma (KC) (also referred to as nonmelanoma skin cancer) is by far the most common form of human cancer. A personal history of KC is well established to be associated with increased risk of recurrent KC and malignant melanoma, a less common yet more fatal form of skin cancer. More surprising is that a substantial body of epidemiologic evidence now indicates that a personal history of KC is significantly associated with an overall elevated risk of noncutaneous malignancies. This association is not limited to one or a few types of cancer but applies across many different types of malignancy. This association has been consistently observed in prospective studies across genders for both major histologic types of KC, basal cell carcinoma and squamous cell carcinoma. The risk of other cancers has been even stronger in those with younger compared with older age of onset of KC. A robust body of evidence lends support to the notion that KC may be a marker of a high cancer-risk phenotype. The underlying mechanisms for this association remain to be elucidated, but the cross-cutting nature of this association across numerous malignancies suggests that research to uncover these mechanisms is a promising line of inquiry that could potentially yield valuable insight into human carcinogenesis.