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• W2808705967 abstract "To the Editor: Exposure to ultraviolet radiation is an important risk factor for melanoma but is also the principal means by which the body synthesizes vitamin D in the skin. Prior studies on the association between 25-OH-D levels and melanoma occurrence and prognosis have shown conflicting results.1Afzal S. Nordestgaard B.G. Bojesen S.E. Plasma 25-hydroxyvitamin D and risk of non-melanoma and melanoma skin cancer: a prospective cohort study.J Invest Dermatol. 2013; 133: 629-636Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 2Newton-Bishop J.A. Beswick S. Randerson-Moor J. et al.Serum 25-hydroxyvitamin D3 levels are associated with Breslow thickness at presentation and survival from melanoma.J Clin Oncol. 2009; 27: 5439-5444Crossref PubMed Scopus (228) Google Scholar To gain further insight into the relationship between serum 25-OH-D levels and later development of melanoma, we conducted a nested case-control study in postmenopausal white women in the Women's Health Initiative Observation Study and the Population Architecture using Genomics and Epidemiology study, which selected 718 melanoma cases and 718 controls without melanoma.3Design of the Women's Health Initiative Clinical Trial and Observational Study. The Women's Health Initiative Study Group.Control Clin Trials. 1998; 19: 61-109Abstract Full Text Full Text PDF PubMed Scopus (2093) Google Scholar, 4Matise T.C. Ambite J.L. Buyske S. et al.The Next PAGE in understanding complex traits: design for the analysis of Population Architecture Using Genetics and Epidemiology (PAGE) Study.Am J Epidemiol. 2011; 174: 849-859Crossref PubMed Scopus (120) Google Scholar The protocol was approved by each participating institution's review board and all women provided written informed consent. 25-OH-D levels were measured by using liquid chromatography–mass spectrometry from stored serum samples taken at baseline. Multivariable conditional logistic regression models were used to evaluate the association between 25-OH-D levels and risk for melanoma. Cox proportional hazards regression was used to estimate hazard ratios for melanoma-specific mortality, which was adjudicated with medial records. Table I shows the baseline characteristics of the Women's Health Initiative participants. Women with higher 25-OH-D concentrations resided in geographic areas of higher sun exposure (in langleys) (P = .003). On average, women who developed melanoma had a 2-ng/mL higher mean 25-OH-D level at baseline than the controls (27.2 ng/mL vs 25.1 ng/mL, P < .0001). At the time of diagnosis, 53.5% of melanoma cases (n = 381) were invasive and 46.5% (n = 331) were in situ. In multivariable models (Table II), women with 25-OH-D levels of 30 ng/mL or higher had a 1.59-fold higher risk for development of invasive and in situ melanoma compared with women with 25-OH-D levels of 20 ng/mL or lower (95% confidence interval [CI], 1.04-2.42; P < .01). Women with 25-OH-D levels between 20.1 and 29.9 ng/mL had a 1.79-fold higher risk for development of melanoma compared with women with 25-OH-D levels of 20 ng/mL or lower (95% CI, 1.22-2.62).Table IBaseline characteristics of women with serum 25-OH-D levels by clinically defined limitsCharacteristic25-OH-D level, ng/mLP value∗Boldface indicates statistical significance.≤20.0 ng/mL(n = 341)20.1-29.9 ng/mL(n = 545)≥30.0 ng/mL(n = 455)Age, y.45 50-59109 (32.0)184 (33.8)160 (35.2) 60-69153 (44.9)236 (43.3)210 (46.2) ≥7079 (23.2)125 (22.9)85 (18.7)Education.08 None-HS21 (6.2)29 (5.4)17 (3.7) Diploma-GED certificate56 (16.6)81 (15.0)84 (18.5) School after HS111 (32.9)227 (42.1)175 (38.6) ≥College degree149 (44.2)202 (37.5)178 (39.2)Vitamin D intake, IU/d.60 <400193 (56.0)327 (60.0)266 (58.5) ≥400148 (43.4)218 (40.0)189 (41.5)Regional solar irradiance, Ly.003 300-325126 (36.95)189 (34.7)125 (27.5) 35072 (21.1)110 (20.2)89 (19.6) 375-38044 (12.9)61 (11.2)49 (10.8) 400-43051 (15.0)81 (14.9)71 (15.6) 475-50048 (14.1)104 (19.1)121 (26.6)Summer season of blood draw75 (23.0)142 (26.1)109 (24.0).32Smoking.16 Never smoked176 (52.5)291 (54.0)207 (46.3) Past smoker141 (42.1)215 (39.9)208 (46.5) Current smoker18 (5.4)33 (6.1)32 (7.2) History of NMSC38 (11.2)65 (12.0)63 (13.9).48Skin type (skin reaction to sun).41 No change in skin color26 (7.9)50 (9.4)43 (9.8) Tans but does not burn107 (32.5)168 (31.7)140 (31.8) Burns, then tans88 (26.8)132 (24.9)100 (22.7) Burns, then tans a minimal amount87 (26.4)126 (23.8)106 (24.1) Burns but does not tan21 (6.4)54 (10.2)51 (11.6)Sun exposure Time outdoors during summer/youth.51<30 min4 (0.01)8 (1.5)10 (2.2)30 min to 2 h63 (18.8)121 (22.6)98 (21.7)>2 h268 (80)407 (75.9)344 (76.1) Time outdoors during summer/this year.83<30 min115 (34.3)172 (32.1)146 (32.2)30 min to 2 h155 (46.3)270 (50.4)224 (49.5)>2 h65 (19.4)94 (17.5)83 (18.3)Usually use sunscreen outside.86 No163 (48.5)253 (47.6)206 (46.5) Yes173 (51.5)279 (52.4)237 (53.5)Information on age, daily vitamin D intake, history of NMSC, and other variables were obtained by questionnaire at baseline. Sun exposure variables were collected in a questionnaire administered at year 4. Baseline characteristics and melanoma risk factors were compared between 3 groups of 25-OH-D levels (≤20 ng/mL, 20-29 ng/mL, and ≥30 ng/mL). Not all adjusted variables are shown.GED, General Educational Development; HS, high school; Ly, langley; NMSC, nonmelanoma skin cancer; 25-OH-D, 25-hydroxyvitamin D.∗ Boldface indicates statistical significance. Open table in a new tab Table IIMultivariate model with key risk factors for incident melanoma in postmenopausal women in the Women's Health Initiative Observational StudyVariableOdds ratio∗Odds ratios are for each covariate in a multivariable model adjusted for age, BMI, education, multivitamin and calcium intake, sun exposure history, history of skin cancer, physical activity, season of blood draw, smoking, time spent outdoors in the summer both in childhood and in adulthood, use of sunscreen, regional solar irradiance (in langleys), and having a medical visit in the last year. (95% CI)P value†Boldface indicates statistical significance.Age, y (ref, 50-59).50 60-691.20 (0.83-1.74) 70-990.98 (0.64-1.49)History of NMSC (yes vs no)4.10 (2.45-6.87)<.0001Calcium intake, mg/d (ref, <800).06 800-12000.75 (0.45-1.25) ≥12000.51 (0.28-0.93)Regional solar irradiance, Ly (ref, 300-325).81 3501.17 (0.75-1.81) 375-3801.42 (0.80-2.50) 400-4301.12 (0.68-1.84) 475-5001.17 (0.75-1.81)Vitamin D intake <400 IU vs ≥400 IU0.80 (0.47-1.38).4325-OH-D level, ng/mL (ref, ≤20.0 ng/mL).011.79 (1.22-2.62) ≥30.01.59 (1.04-2.42)Last medical visit within 1 year1.65 (1.09-2.48).02Women in the Women's Health Initiative Observational Study were mailed annual questionnaires to report health outcomes, including diagnosis with melanoma, which was confirmed by review of medical records and pathology reports. Our multivariate model was adjusted for all the factors listed in this table. Not all variables are shown.CI, Confidence interval; Ly, langley; NMSC, nonmelanoma skin cancer; 25-OH-D, 25-hydroxyvitamin D; ref, reference.∗ Odds ratios are for each covariate in a multivariable model adjusted for age, BMI, education, multivitamin and calcium intake, sun exposure history, history of skin cancer, physical activity, season of blood draw, smoking, time spent outdoors in the summer both in childhood and in adulthood, use of sunscreen, regional solar irradiance (in langleys), and having a medical visit in the last year.† Boldface indicates statistical significance. Open table in a new tab Information on age, daily vitamin D intake, history of NMSC, and other variables were obtained by questionnaire at baseline. Sun exposure variables were collected in a questionnaire administered at year 4. Baseline characteristics and melanoma risk factors were compared between 3 groups of 25-OH-D levels (≤20 ng/mL, 20-29 ng/mL, and ≥30 ng/mL). Not all adjusted variables are shown. GED, General Educational Development; HS, high school; Ly, langley; NMSC, nonmelanoma skin cancer; 25-OH-D, 25-hydroxyvitamin D. Women in the Women's Health Initiative Observational Study were mailed annual questionnaires to report health outcomes, including diagnosis with melanoma, which was confirmed by review of medical records and pathology reports. Our multivariate model was adjusted for all the factors listed in this table. Not all variables are shown. CI, Confidence interval; Ly, langley; NMSC, nonmelanoma skin cancer; 25-OH-D, 25-hydroxyvitamin D; ref, reference. Women with melanoma and 25-OH-D levels of 20 ng/mL or lower at baseline were 2.75 times more likely to die of melanoma than women with 25-OH-D levels between 20.1 and 29.9 ng/mL (95% CI 1.14-6.65; P =.025), but there was no significant relationship in death by melanoma when comparing women with 25-OH-D levels of 20 ng/mL or lower at baseline to women with 25-OH-D levels of 30 ng/mL or higher (hazard ratio, 1.43; 95% CI, 0.66-3.12; P = .396). The lack of significant association in the 30 ng/mL or higher strata could be due to the smaller sample size in this group (Table I). In our study, higher serum 25-OH-D levels were associated with a greater risk for development of melanoma, which may be related to higher ultraviolet radiation exposure. In contrast, low 25-OH-D levels before melanoma diagnosis were associated with a higher risk for melanoma-related death. Because 25-OH-D levels are higher in more physically active, healthier individuals, it is possible that these levels are serving as a marker for overall health.5Brock K. Huang W.Y. Fraser D.R. et al.Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large US sample of healthy middle-aged men and women.J Steroid Biochem Mol Biol. 2010; 121: 462-466Crossref PubMed Scopus (185) Google Scholar It is important to note, however, that the difference in 25-OH-D levels between the melanoma and control group was small (2 ng/mL) and of unclear physiologic significance. Our data demonstrate the challenge of studying the association of vitamin D levels with melanoma risk, because the measurement of 25-OH-D level is confounded by sunlight exposure, which is a major risk factor for the development of melanoma. The cause-and-effect relationship between serum 25-OH-D level and melanoma incidence and prognosis is important to explore, and carefully designed clinical trials are needed." @default.
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• W2808705967 title "Association of 25-hydroxyvitamin D levels and cutaneous melanoma: A nested case-control study of the Women's Health Initiative Observation Study" @default.
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