title: Genes of detoxification are important modulators of hereditary medullary thyroid carcinoma risk.
abstract: BACKGROUND
  Different inherited profiles of genes involved in cellular mechanisms of activation and detoxification of carcinogenic products can provide specific protection or determine the risk for cancer. Low-penetrance polymorphic genes related to the biotransformation of environmental toxins have been associated with susceptibility to and the phenotype of, human tumours.
  
  
  OBJECTIVE
  To investigate the role of germline inheritance of polymorphisms in CYP1A2*F, CYP1A1 m1, GSTP1, NAT2 and TP53 genes in hereditary medullary thyroid carcinoma (HMTC) patients.
  
  
  METHODS
  This study was developed in University of Campinas (Unicamp).
  
  
  METHODS
  We studied 132 patients with HMTC, 88 first-degree relatives of HMTC patients and 575 control individuals.
  
  
  METHODS
  All patients with MTC and their relatives were sequenced for the RET gene and five genes were genotyped using TaqMan(®) system.
  
  
  RESULTS
  We observed that the inheritance of CYP1A2*F (OR = 2·10; 95% CI = 1·11-3·97; P = 0·022), GSTP1 (OR = 4·41; 95% CI = 2·47-7·88; P < 0·001) and NAT2 (OR = 2·54; 95% CI = 1·16-5·58; P = 0·020) variants increased the risk for HMTC. In addition, multiple regression analysis showed that the inheritance of GSTP1 polymorphisms was associated with the diagnosis in older patients (B = 8·0229; 95% IC = ± 5·5735; P = 0·0054). Concerning the group of HTMC relatives, CYP1A2*F (OR = 2:40; 95% CI = 1·19-4·86; P = 0·015), CYP1A1 m1 (OR = 2·79; 95% CI = 1:04-7·51; P = 0·042), GSTP1 (OR = 2·86; 95% IC = 1·53-5·32; P < 0·001) and NAT2 (OR = 2·25; 95% IC = 1·20-4·22; P = 0·012) were associated with HMTC risk.
  
  
  CONCLUSIONS
  We have demonstrated that the inheritance of specific genes determining the individual response to environmental toxins may contribute to the risk and phenotypic variability that exists in patients with HMTC. Moreover, we identified a group at risk in relatives of HMTC patients.
authors.affiliation: Faculty of Medical Sciences, Laboratory of Cancer Molecular Genetics, University of Campinas (FCM-Unicamp), Campinas, Brazil.
authors.forename: R B
authors.initials: RB
authors.lastname: Barbieri
authors.forename: N E
authors.initials: NE
authors.lastname: Bufalo
authors.forename: L L
authors.initials: LL
authors.lastname: Cunha
authors.forename: L V M
authors.initials: LV
authors.lastname: Assumpção
authors.forename: R M B
authors.initials: RM
authors.lastname: Maciel
authors.forename: J M
authors.initials: JM
authors.lastname: Cerutti
authors.forename: L S
authors.initials: LS
authors.lastname: Ward
mesh_terms: D000293:Adolescent; D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D018278:Carcinoma, Neuroendocrine; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C504573:CYP1A2 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human