title: Prognostic Value of 25-hydroxyvitamin D3 Levels at Diagnosis and During Follow-up in Melanoma Patients.
abstract: BACKGROUND
  A low 25-hydroxyvitamin D3 (25(OH)D3) serum concentration at melanoma diagnosis might be associated with worse survival. We prospectively studied the prognostic value of 25(OH)D3 at diagnosis and during follow-up.
  
  
  METHODS
  MelanCohort is a cohort of invasive melanoma patients. Serum 25(OH)D3 was measured by mass spectrometry and standardized on month of blood drawn, age, sex, and body mass index (BMI). Role of 25(OH)D3 levels and risk of relapse was analyzed in a Cox proportional hazards model adjusting for age, sex, BMI, and American Joint Committee on Cancer (AJCC) stage. All statistical tests were two-sided.
  
  
  RESULTS
  One thousand one hundred seventy-one patients were included. 25(OH)D3 levels at diagnosis (median = 49.0 nmol/L) were inversely correlated with prognostic factors such as AJCC stage (P < .001 Kruskal-Wallis), Breslow's thickness (P < .001 Spearman correlation), and ulceration (P < .001 Kruskal-Wallis), but not with risk of relapse. Changes in 25(OH)D3 levels during follow-up were associated with worse prognosis: With a third quartile Q3 of average change per year (-0.30 to 4.60 nmol/L/Y) used as reference, hazard ratios for the first, second, and fourth quarters were 1.94 (95% confidence interval [CI] = 1.36 to 2.76), 1.23 (95% CI = 0.85 to 1.78), and 1.61 (95% CI = 1.14 to 2.28), respectively. In sensitivity analyses, no changes were observed either by AJCC stage, number of 25(OH)D3 measures performed, or by 25(OH)D3 level at baseline. No evidence of reverse causation was identified. Analyses performed on overall survival yielded similar results.
  
  
  CONCLUSIONS
  We show that 25(OH)D3 variation during follow-up is an independent melanoma prognostic marker, but not its level at diagnosis. Previously reported associations between low 25(OH)D3 level at diagnosis and poor prognosis seem to be due to insufficient adjustment for prognostic factors.
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB). philippe.saiag@uvsq.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saiag
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Philippe
authors.initials: P
authors.lastname: Aegerter
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Dominique
authors.initials: D
authors.lastname: Vitoux
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Celeste
authors.initials: C
authors.lastname: Lebbé
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Pierre
authors.initials: P
authors.lastname: Wolkenstein
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupin
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Vincent
authors.initials: V
authors.lastname: Descamps
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Selim
authors.initials: S
authors.lastname: Aractingi
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Elisa
authors.initials: E
authors.lastname: Funck-Brentano
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Philippe
authors.initials: P
authors.lastname: Autier
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Miruna
authors.initials: M
authors.lastname: Dragomir
authors.affiliation: Université de Versailles St-Quentin, EA 4340, F-92104 Boulogne-Billancourt, France (PS, EFB); AP-HP, Hôpital Ambroise Paré, Service de Dermatologie Générale et Oncologique, F-92104 Boulogne-Billancourt, France (PS, EFB); Université de Versailles St-Quentin, UMR-S 1168, Saint Quentin-en-Yvelines, France (PA); INSERM, U1168 F-94807, Villejuif, France (PA); AP-HP, Hôpital Ambroise Paré, Unité de recherche clinique et département de santé Publique, F-92104 Boulogne-Billancourt, France (PA); APHP, service de Biochimie, Hôpital Saint-Louis, F-75010 Paris, France (DV); APHP, service de Dermatologie, Hôpital Saint-Louis, F-75010 Paris, France (CL); Université Paris Diderot, F-75010 Paris, France (CL, VD); APHP, service de Dermatologie, Hôpital Henri Mondor, F-94000 Créteil, France (PW); Université Paris-Est Créteil, F-94000 Créteil, France (PW); APHP, service de Dermatologie, Pavillon Tarnier, Hôpital Cochin, F-75014 Paris, France (ND, SA); Université Paris Descartes, F-75014 Paris, France (ND, SA); APHP, service de Dermatologie, Hôpital Bichat, F-75018 Paris, France (VD); Strathclyde Institute for Global Public Health at iPRI, F-69000 Lyon, France (PA, MB); International Prevention Research Institute (iPRI), F-69000 Lyon, France (PA, MD, MB).
authors.forename: Mathieu
authors.initials: M
authors.lastname: Boniol
mesh_terms: D000328:Adult; D000368:Aged; D002112:Calcifediol / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry; D008545:Melanoma / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D014815:Vitamins / Q000097:blood*; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014815:Vitamins; D002112:Calcifediol