Molecular Epidemiology of Cutaneous Malignant Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Study type: Observational

Summary: 
      This case-control study was planned to investigate the link of solar radiation with gene
      damage, host factors, and DNA repair proficiency in cutaneous malignant melanoma (CMM) risk.
      The hypothesis was that impaired DNA repair proficiency is associated with an increased risk
      of CMM due to unrepaired DNA damage, particularly in subjects with dysplastic nevi, poor
      tanning ability or genetic susceptibility.

      The study was reviewed as an RO1 Grant from the National Cancer Institute in 1995. Subject
      enrollment, which included clinical evaluation, epidemiologic questionnaires, and skin and
      blood sample collection, was completed in 1999 on approximately 180 melanoma cases and 180
      controls identified in Italy. The study protocol and consent form both included the
      measurement of genetic and biochemical factors and DNA repair capacity. DNA repair
      proficiency was measured in lymphocytes by the host cell reactivation assay, and sun exposure
      was evaluated by means of a detailed questionaire. Photographs of the back of the subjects
      were taken to allow nevi count. Minimal erythemal dosage was measured in all subjects to
      estimate skin sun sensitivity 24 hours after skin's UV-irradiation. Skin color was
      ascertained on the inner side of the forearm by means of a Minolta chromometer.

      The aim of this protocol is to continue analysis of the biological samples already collected,
      as originally outlined in the study protocol. In particular, we plan to measure polymorphisms
      in genes that may lead to susceptibility to melanoma. Initially we will concentrate on
      variation in genes involved in repairing damaged DNA, but plan to look at a broad group of
      candidate susceptibility genes.
    

Detailed description: 
      The original case-control study was planned to investigate the link of solar radiation with
      gene damage, host factors, including also genetic variants, and DNA repair proficiency in
      cutaneous malignant melanoma (CMM) risk, in subjects from the Mediterranean area,
      characterized by a wide range of pigmentary characteristics and intense sun exposure. This
      study was reviewed and funded as an R01 grant from the National Cancer Institute in 1995.
      Subject enrollment, which included clinical evaluation, epidemiologic questionnaires, and
      skin and blood sample collection, was completed in 1999 on approximately 180 melanoma cases
      and 180 controls identified in Italy. The study protocol and consent form both included the
      measurement of genetic and biochemical factors, and DNA repair capacity. DNA repair
      proficiency was measured in lymphocytes by the host cell reactiviation assay, and sun
      exposure was evaluated by means of a detailed questionnaire. Minimal erythemal dosage was
      measured in all subjects to estimate skin sun sensitivity 24 hours after skin's
      UVirradiation. Skin color was ascertained on the inner side of the forearm by means of a
      minolta chromometer.

      The aim of this protocol was to continue the analysis of the biological samples and data
      already collected, as originally outlined in the study protocol. However, the original sample
      size was small and precluded specific analyses of gene-environment interaction crucial for
      the understanding of the etiology of melanoma. We have identified other collaborators willing
      to share their data and sample with us to increase the power for statistical analyses. We
      obtained approval (amendments to 02-C-N035 approved in November 2006, September 2008,
      December 2010, and June 2011) to use the DNA samples and data collected in four studies
      conducted by investigators at the University of L'Aquila, Italy, University of Genoa, Italy,
      Istituto Valenciano de Oncologia, Valencia, Spain, and the New York University School of
      Medicine, respectively. We have obtained approval with stipulations in August 2014 to also
      include samples and data collected from the Papa Giovanni XXII Hospital in Bergamo, Italy and
      the University of Athens, Greece. We are now responding to the stipulations and asking to
      further include samples from the University of Padua and the Hospital Clinic of Barcelona
      within the same study.

      We are currently analyzing genes in several pathways, including pigmentation, DNA repair,
      immune-related functions and those involved in the transition from nevi to melanoma (genes in
      the cell cycle, telomere, signaling pathways, etc). With the additional samples we plan to
      conduct a GWAS analysis of melanoma in Mediterranean countries and a molecular analysis of
      melanoma tissue lesions for an improved classification of the disease and its association
      with melanoma progression.
    

Observational model: Other
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Cases from hospitals; Controls from the general populations
      
Keywords: DNA Repair; Genes; Pigmentation; Skin Cancer; Sun Exposure