Malignant melanoma in-situ (MMIS) has been associated with the risk of invasive melanoma, either through invasive transformation or as a marker for de novo invasive melanoma. However, while risk of invasive melanoma has been extensively studied, very little data exists on phenotypic risk factors of MMIS. Objectives: In this study, we evaluated the risk of MMIS according to host phenotypic characteristics amongst a large population of US women and men. Methods: We used data from three prospective cohort studies, the Nurse's Health Study 1 and 2 (NHS, NHS2), and the Health Professionals Follow-up Study (HPFS). Data were collected via biennial questionnaires from 44,998 males and 205,153 females over a 28, 20 and 22 year period for NHS1, NHS2, and HPFS, respectively. 1,097 melanoma in-situ lesions were identified and confirmed via pathology reports. Risk factors were family history of melanoma, number of atypical (>3mm) nevi on an extremity, childhood/adolescent sunburn reaction, number of childhood/adolescent sunburns and natural hair color at age 21. Age-adjusted and multivariate regression analysis was performed. Further sub-analysis in NHS evaluated MMIS risk based on Fitzpatrick skin type. Results: Individuals with a family history of melanoma had increased risk of MMIS in all three studies, NHS mvRR 1.51 (95% CI 1.13-2.02), NHS2 RR 1.95 (95% CI 1.42-2.69), HPFS RR 2.72 (95% CI 1.61-4.59). Three or more moles on the extremity were also associated with increased risk of MMIS, NHS RR 1.62 (95% CI 1.19-2.21), NHS2 RR 1.63 (95% CI 1.08-2.45), HPFS RR 1.93 (95% CI 1.21-3.08). In individuals with 6 or more moles on an extremity, the relative risk increased to reflect threefold risk, NHS mvRR 2.77 (95% CI 2.02-3.78), NHS2 mvRR 2.95 (95% CI 2.25-3.88), HPFS mvRR 2.79 (95% CI 1.75-4.46) (P for trend <0.0001). Among women, but not men, red hair was a significant risk factor, NHS mvRR 1.55 (95% CI 1.09-2.21), NHS2 mvRR 2.10 (95% CI 1.34-3.30) as was ≥3 childhood sunburns, NHS mvRR 1.54 (95% CI 1.13-2.09), NHS2 mvRR 1.41 (95% CI 1.00-1.98). Fitzpatrick skin type was determined in NHS and was associated with significant increased risk of MMIS, Type I mvRR 1.97 (95% CI 1.34-2.89), Type II mvRR 1.61 (95% CI 1.19-2.17), Type III 1.47 (95% CI 1.08-1.98) (P for trend =0.0009). Conclusions: In this study of US women and men, family history of melanoma and more than three moles on an extremity were significantly associated with increased risk of MMIS, similar to our previous findings for invasive melanoma. Moreover, increasing number of moles was associated with increasing relative risk. For women, red hair color, frequent childhood sunburns and Fitzpatrick skin type I, II and III were associated with an increased risk of MMIS. Elucidating these risk factors and their relative contribution for MMIS risk may be helpful in identifying individuals with specific phenotypic risk factors.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5500. doi:1538-7445.AM2012-5500