Keratinocyte Carcinoma and Risk for Another Type of Cancer: Assessment of a Dose-response Relationship

Patients and Methods

This study was approved by the institutional review board of the Medical University of South Carolina (MUSC). This study was a clinic-based matched case-control study that included recruitment of two groups of patients: A group of n=50 participants with a history of both KC and another cancer and another group with n=50 participants with a history of KC only. The two study groups were matched for sex, age, and KC histologic type. Possible combinations of KC histologic types were SCC only, BCC only, and both BCC and SCC. Missing data on the number of KC lesions necessitated exclusion of four participants. The final study population for this report included 48 matched pairs.

Participation was limited to non-Hispanic Caucasians between 30-80 years old who were able to speak and understand English. This study was limited to non-Hispanic Caucasians because the risk of KC is predominant within this group (5). Individuals who were prisoners, institutionalized, pregnant, or cognitively impaired were not eligible to participate in the study.

During 2013-2014, participants were recruited from MUSC dermatology clinics. Prior to their clinic appointment, eligible patients were mailed an information packet. The study coordinator then contacted patients by telephone to assess their interest and eligibility. An appointment was scheduled during the clinic visit for those eligible and interested in participating, during which participants completed an informed consent form, HIPPA authorization, medical release forms, and an interviewer-administered questionnaire. Patients were compensated for participating in the study.

Data from participants were collected via an interviewer-administered questionnaire as well as a medical record review. The questionnaire consisted of questions regarding socio-demographic factors, health status, comorbidities, skin cancer risk factors, risk factors for other types of cancer, and other lifestyle factors. Information obtained from medical records consisted of body mass index, comorbidities other than cancer, KC history with regard to histologic type, location, number of lesions, and other cancer history with regard to location, cancer stage, and treatment. Self-reported history of other types of cancer was confirmed via medical record review including linkage to the South Carolina Central Cancer Registry.

Medical record data were prioritized over self-reported information for measuring KC history because although self-reported patient information is relatively accurate concerning skin cancer diagnoses, the accuracy decreases with respect to specific details such as the number of skin cancers and the histologic type (7, 8). In instances where the medical record data were missing or lacked information on the patient's skin cancer history, the patient's self-reported history was used.

In the data analyses, the dose-response association was assessed for BCC, SCC and for the total KC combined. The mean number of KC lesions were compared between groups using a paired t-test. Matched odds ratios and 95% confidence intervals were calculated using conditional logistic regression models to analyze the frequency of KC lesions between groups in relation to the risk of a type of cancer other than KC. p-Values for trend in these odds ratios were calculated via a Cochran-Mantel-Haenszel test by fitting a single variable within ordered categories in a conditional logistic regression model. Additional variables adjusted for were education, body mass index, and cigarette smoking because each is a cross-cutting risk factor for many types of cancer. Further adding to its potential confounding role, cigarette smoking is associated with risky sun exposure behaviors even in those with a personal history of skin cancer (9).