Risk Factors for Melanoma by Body Site for Whites Eunyoung Cho, 1 Bernard A. Rosner, 1,2 and Graham A. Colditz 1,3,4 1 Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital; Departments of 2 Biostatistics and 3 Epidemiology, Harvard School of Public Health; and 4 Harvard Center for Cancer Prevention, Boston, Massachusetts Abstract It has been hypothesized that cutaneous melanoma at different anatomic sites develops through divergent path- ways. We examined this hypothesis prospectively. We followed 152,949 women and 25,204 men free of cancer at baseline for up to 14 years in three large prospective studies. We examined risk factors for melanoma by anatomic location (head or neck, trunk, upper extremity, and lower extremity). Polytomous logistic regression was used to test the differ- ence among risk factors by location of melanoma. A total of 511 incident cases of invasive melanoma (49 head or neck, 188 trunk, 98 upper extremity, and 176 lower extremity) were included in the analysis. Compared with females, males had a higher risk of developing melanoma on the head or neck and trunk. History of severe and painful sunburn was most strongly related to melanoma of upper extremity; individuals with >10 burns had a 6.86-fold (95% confidence interval, 2.62- 18.00) higher risk of melanoma of upper extremity compared with those with no burns (P for trend < 0.0001; P for difference by body site = 0.04). Number of moles was most strongly related to melanoma of the trunk; the multivariate relative risk for having >10 moles was 4.67 (95% confidence interval, 3.07-7.11) compared with having no moles (P for trend < 0.0001; P for difference by body site = 0.04). Age, family history of melanoma, and hair color did not statistically differ by anatomic site of the cancer. These data support divergent etiologic pathways of melanoma develop- ment by anatomic sites. (Cancer Epidemiol Biomarkers Prev 2005;14(5):1241 – 4) Introduction Incidence of cutaneous malignant melanoma has been increas- ing in the United States (1). However, the etiology of melanoma has not been fully understood, except that sun exposure is a risk factor. It has been hypothesized that melanoma develops through multiple etiologic pathways. Previous studies have found that traditional melanoma risk factors have different associations with melanoma by body sites (2). However, there has been no prospective study to examine this hypothesis. We have reported that higher age, male sex, family history of melanoma, higher number of nevi, history of severe sunburn, and light hair color were each associated with elevated risk of melanoma using data from three large cohort studies of women and men (3). Using the same data set, we examined these risk factors for melanoma by location of cancer. Although we have previously examined self-reported mole counts and melanoma by site in one of the cohorts, that analysis included cases from only the first 8 years of follow-up and used retrospective case-control design (4). Materials and Methods Study Population. The Nurses’ Health Study (NHS) enrolled 121,700 female registered nurses ages 30 to 55 years in 1976. NHS II enrolled 116,671 female registered nurses ages 25 to 42 years in 1989. The Health Professionals Follow- up Study (HPFS) included 51,529 male health professionals (dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists) ages 40 to 75 years in 1986. These participants responded to a questionnaire about their medical histories and lifestyles. We have sent follow-up question- naires to the cohorts biennially to collect and update information regarding individual characteristics, behaviors, and diagnosed diseases. Deaths were reported by family members or by the postal service in response to the follow-up questionnaire or through the National Death Index for nonresponders (5). To conduct a completely prospective analysis, we used 1986 as a baseline for the NHS and 1992 for the HPFS because the information on several risk factors for melanoma was collected in these years. Participants who reported diagnosis of cancer other than nonmelanoma skin cancer were excluded at baseline and censored at time of diagnosis during follow-up. Cases of melanoma in situ were also excluded at baseline and during follow-up. Because most of the participants were Caucasians and melanoma is rare in other races, we excluded other races. We included only those who answered questions on traditional melanoma risk factors, including age, family history of melanoma, number of nevi (moles), hair color, and history of severe sunburn. A total of 178,153 participants (62,755 in the NHS, 90,194 in the NHS II, and 25,204 in the HPFS) were included in the analysis. The study was approved by the Human Research Commit- tees at the Harvard School of Public Health and the Brigham and Women’s Hospital. Assessment of Melanoma Risk Factors. Each cohort collected information on age, family history of melanoma, number of acquired melanocytic nevi on arms (legs in the NHS II) larger than 3 mm in diameter (as a proxy for the total body nevi count), natural hair color, and history of severe sunburn. Melanoma Case Confirmation. Within the study popula- tions over the periods of follow-up for these analyses, 536 NHS, 414 NHS II, and 282 HPFS members reported a diagnosis of melanoma. Medical records were obtained for 451 of the NHS, 311 of the NHS II, and 203 of the HPFS and reviewed by a dermatologist. We excluded in situ melanomas (171 NHS, 103 NHS II, and 82 HPFS). Information on anatomic location of Received 8/24/04; revised 11/8/04; accepted 1/11/05. Grant support: Harvard Skin Specialized Program of Research Excellence and research grant CA87969 from NIH. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Requests for reprints: Eunyoung Cho, Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115. E-mail: eunyoung.cho@channing.harvard.edu Copyright D 2005 American Association for Cancer Research. Cancer Epidemiology, Biomarkers & Prevention 1241 Cancer Epidemiol Biomarkers Prev 2005;14(5). May 2005