title: Role of genetic polymorphisms in NFKB-mediated inflammatory pathways in response to primary chemoradiation therapy for rectal cancer.
abstract: OBJECTIVE
  To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT).
  
  
  METHODS
  Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models.
  
  
  RESULTS
  The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037).
  
  
  CONCLUSIONS
  Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.
authors.affiliation: Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain; Department of Radiation Oncology, Madrid Oncology Institute (Group IMO), Murcia, Spain.
authors.forename: Maia
authors.initials: M
authors.lastname: Dzhugashvili
authors.affiliation: Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain.
authors.forename: Ginés
authors.initials: G
authors.lastname: Luengo-Gil
authors.affiliation: Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: García
authors.affiliation: Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: González-Conejero
authors.affiliation: Department of Pathology, University Hospital Santa Lucía, Cartagena, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Conesa-Zamora
authors.affiliation: Department of Radiation Oncology, University Hospital Santa Lucía, Cartagena, Spain.
authors.forename: Pedro Pablo
authors.initials: PP
authors.lastname: Escolar
authors.affiliation: Department of Radiation Oncology, University General Hospital Gregorio Marañón, Madrid, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Calvo
authors.affiliation: Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.affiliation: Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain. Electronic address: frayala@um.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ayala de la Peña
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004751:Enteritis / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D011349:Proctitis / Q000235:genetics; D011725:Pyridines / Q000008:administration & dosage; D011836:Radiation Tolerance / Q000235:genetics*; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D009944:Organoplatinum Compounds; D011725:Pyridines; C431073:oxiplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D005472:Fluorouracil