Original Paper

Digestive Diseases and Sciences

, Volume 53, Issue 5, pp 1417-1421

First online:

CYP1B1 Polymorphisms and K-ras Mutations in Patients with Pancreatic Ductal Adenocarcinoma

  • Marta Crous-BouAffiliated withInstitut Municipal d’Investigació Mèdica (IMIM), CIBER de Epidemiología y Salud Pública (CIBERESP)School of Medicine, Universitat Autònoma de Barcelona
  • , Immaculata De VivoAffiliated withHarvard School of Public HealthChanning Laboratory, Brigham and Women’s Hospital
  • , Miquel PortaAffiliated withInstitut Municipal d’Investigació Mèdica (IMIM), CIBER de Epidemiología y Salud Pública (CIBERESP)School of Medicine, Universitat Autònoma de Barcelona Email author 
  • , José A. PumaregaAffiliated withInstitut Municipal d’Investigació Mèdica (IMIM), CIBER de Epidemiología y Salud Pública (CIBERESP)
  • , Tomàs LópezAffiliated withInstitut Municipal d’Investigació Mèdica (IMIM), CIBER de Epidemiología y Salud Pública (CIBERESP)
  • , Joan AlguacilAffiliated withInstitut Municipal d’Investigació Mèdica (IMIM), CIBER de Epidemiología y Salud Pública (CIBERESP)Department of Environmental Biology & Public Health, Universidad de Huelva
  • , Eva MoralesAffiliated withInstitut Municipal d’Investigació Mèdica (IMIM), CIBER de Epidemiología y Salud Pública (CIBERESP)
  • , Núria MalatsAffiliated withInstitut Municipal d’Investigació Mèdica (IMIM), CIBER de Epidemiología y Salud Pública (CIBERESP)
  • , Juli RifàAffiliated withHospital Son Dureta
    • , David J. HunterAffiliated withHarvard School of Public HealthChanning Laboratory, Brigham and Women’s Hospital
    • , Francisco X. RealAffiliated withInstitut Municipal d’Investigació Mèdica (IMIM), CIBER de Epidemiología y Salud Pública (CIBERESP)Universitat Pompeu Fabra
    • , For the PANKRAS II Study Group

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Abstract

The frequency of CYP1B1 polymorphisms in pancreatic cancer has never been reported. There is also no evidence on the relationship between CYP1B1 variants and mutations in ras genes (K-, H- or N-ras) in any human neoplasm. We analyzed the following CYP1B1 polymorphisms in 129 incident cases of pancreatic ductal adenocarcinoma (PDA): the m1 allele (Val to Leu at codon 432) and the m2 allele (Asn to Ser at codon 453). The calculated frequencies for the m1 Val and m2 Asn alleles were 0.45 and 0.68, respectively. CYP1B1 genotypes were out of Hardy–Weinberg equilibrium; this was largely due to K-ras mutated PDA cases. The Val/Val genotype was over five times more frequent in PDA cases with a K-ras mutation than in wild-type cases (OR = 5.25; P = 0.121). In PDA, polymorphisms in CYP1B1 might be related with K-ras activation pathways.

Keywords

Pancreatic neoplasms CYP1B1 polymorphisms K-ras oncogene ras genes