title: POMC and TP53 genetic variability and risk of basal cell carcinoma of skin: Interaction between host and genetic factors.
abstract: BACKGROUND
  Basal cell carcinoma (BCC) of the skin is the most common neoplasm among the Caucasian population of the western world. Ultraviolet (UV) radiation-induced p53 activation promotes cutaneous pigmentation by increasing transcriptional activity of pro-opiomelanocortin (POMC) in the skin. Induction of POMC/α-melanocyte-stimulating hormone (α-MSH) activates the melanocortin 1 receptor (MC1R), resulting in skin pigmentation. The tumor suppressor p53 is a key player in stress responses that preserve genomic stability, responding to a variety of insults including DNA damage, hypoxia, metabolic stress and oncogene activation. Malfunction of the p53 pathway is an almost universal hallmark of human tumors. Polymorphisms in the gene encoding p53 (TP53) alter its transcriptional activity, which in turn may influence the UV radiation-induced tanning response.
  
  
  OBJECTIVE
  The aim of the present work is to test association between POMC and TP53 genetic variability, the possible interplay with host factors and the risk of basal cell carcinoma of skin.
  
  
  METHODS
  We covered the variability of the two genes we used 17 tagging polymorphisms in 529 BCC cases and 532 healthy controls. We have also tested the possible interactions between the genetic variants and three known risk factors for BCC: skin complexion, sun effect and skin response to sun exposure.
  
  
  RESULTS
  We did not observe any statistically significant association between SNPs in these two genes and BCC risk overall, nor interactions of SNPs with known BCC risk factors. However we found that, in the group of subjects with lower sun exposure, carriers of one copy of the C allele of the TP53 SNP rs12951053 had a decreased risk of BCC (OR=0.28, 95% CI 0.12-0.62, P=0.002).
  
  
  CONCLUSIONS
  We have observed that the interplay of an environmental risk factor and one polymorphism in TP53 gene could modulate the risk of BCC.
authors.affiliation: German Cancer Research Center DKFZ, Heidelberg, Germany. c.rizzato@dkfz.de
authors.forename: Cosmeri
authors.initials: C
authors.lastname: Rizzato
authors.forename: Dominique
authors.initials: D
authors.lastname: Scherer
authors.forename: Peter
authors.initials: P
authors.lastname: Rudnai
authors.forename: Eugen
authors.initials: E
authors.lastname: Gurzau
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Koppova
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
mesh_terms: D000368:Aged; D002280:Basal Cell Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics*; D012880:Skin Pigmentation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D044102:Receptor, Melanocortin, Type 1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011333:Pro-Opiomelanocortin