Basal cell carcinoma (BCC) is the most common malignancy in the United States; however, it has beenrelatively understudied in epidemiologic research. Temporal trends indicate that BCC incidence is increasingoverall, in young adults, and especially in young women. Data from 'early onset' cases support the conceptthat there are at least two different subgroups accounting for BCCs in individuals below the age of 40?agroup with single tumors whose incidence is increasing, presumably due to environmental factors, and agroup with multiple tumors whose incidence is stable and who probably have hereditary predisposition toBCCs. The purpose of this study is to assess genetic and environmental risk factors for early onset BCCsand explore the interaction between these factors. This study is an outgrowth of our previous work showingthat the PTCH gene underlies both hereditary and sporadic BCCs but applies and extends this work at apopulation level, with careful consideration of environmental contributions to the disease incidence.Five hundred cases with early onset BCC and 500 controls with benign skin conditions will be recruited fromthe Yale dermatopathology database for interviews and collection of biological samples. Questionnaire datawill be used to assess potential environmental factors that might be related to the increased incidence,especially artificial tanning, excessive solar radiation exposure, smoking, and obesity. The interactionbetween these environmental variables and genetic variants of MC1R, known to relate to skin cancersusceptibility, will be assessed. Tumors from selected subjects in whom BCC risk appears to be relatedstrongly to a particular environmental exposure will undergo sequencing of the PTCH gene to relate thereported exposure to 'signature mutations' in DNA. Subjects with large numbers of BCCs or particularlyearly age of onset of BCCs will have detailed genetic studies to determine if they have a known hereditarydisorder, and if not, to identify novel BCC predisposition genes.Risk factor data are needed to serve as a basis to guide preventive interventions. For example, strongevidence that tanning bed use is an important etiologic factor in early onset BCC, with supporting evidenceshowing mutational spectra consistent with UVB mutations, could form the basis for stronger legislation toprevent tanning bed use by minors. Alternatively, if smoking or other risk factors are more stronglyassociated, this suggests a different intervention strategy to reduce the disease. Identification of underlyingpredisposition genes may help target efforts at prevention to particular genetic subgroups. Thus, thisetiologic work is highly and immediately translatable into preventive interventions aimed at reducing theincidence of this exceedingly common malignancy.
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