title: Interleukin-1β genotype and circulating levels in cancer patients: metastatic status and pain perception.
abstract: OBJECTIVE
  Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients.
  
  
  METHODS
  Serum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters.
  
  
  RESULTS
  IL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p=0.032, Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR=4.074, p=0.010, Pearson χ(2) test). Among the female patients presenting metastatic disease and carriers of the TT genotype we observed a trend to lower levels of IL1-β (p=0.053, Pearson χ(2) test).
  
  
  CONCLUSIONS
  Our results indicate that genetic variation at IL1-β gene may influence serum levels of IL1-β, with proportional consequences in cancer-related pain.
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Molecular Oncology GRP and Virology LB, Portuguese Institute of Oncology-Porto, Porto, Portugal; IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, Advanced Institute of Health Sciences - North, CESPU, CRL, Gandra, Portugal. Electronic address: anacorreiadeoliveira@gmail.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Oliveira
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, Advanced Institute of Health Sciences - North, CESPU, CRL, Gandra, Portugal; Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto, Portugal; Center of Forensic Sciences (CENCIFOR), Portugal.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Dinis-Oliveira
authors.affiliation: Molecular Oncology GRP and Virology LB, Portuguese Institute of Oncology-Porto, Porto, Portugal.
authors.forename: Augusto
authors.initials: A
authors.lastname: Nogueira
authors.affiliation: Palliative Care Unit, Portuguese Institute of Oncology-Porto, Porto, Portugal.
authors.forename: Ferraz
authors.initials: F
authors.lastname: Gonçalves
authors.affiliation: Palliative Care Unit, Portuguese Institute of Oncology-Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Silva
authors.affiliation: Medical Oncology Department, Francisco Gentil Portuguese Institute of Oncology, Porto, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Vieira
authors.affiliation: IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, Advanced Institute of Health Sciences - North, CESPU, CRL, Gandra, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Silvestre
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Félix
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: Molecular Oncology GRP and Virology LB, Portuguese Institute of Oncology-Porto, Porto, Portugal; ICBAS, Abel Salazar Institute for the Biomedical Sciences, Porto, Portugal; Faculty of Health Sciences of Fernando Pessoa University, Porto, Portugal; LPCC, Portuguese League Against Cancer, Regional Center of the North, Porto, Portugal. Electronic address: ruimedei@ipoporto.min-saude.pt.
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000235:genetics; D053582:Interleukin-1alpha / Q000097:blood / Q000235:genetics; D053583:Interleukin-1beta / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D009369:Neoplasms / Q000097:blood / Q000235:genetics*; D010146:Pain / Q000097:blood / Q000235:genetics*; D058748:Pain Perception / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C508584:IL1A protein, human; C508585:IL1B protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta
keywords: 3954C>T; Cancer-related pain; Interleukin-1; Metastatic disease; Polymorphisms