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

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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.

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Abbreviations

PANKRAS:

Multicenter prospective study on the role of the K-ras and other genetic alterations in the diagnosis, prognosis, and etiology of pancreatic and biliary diseases

PDA:

Pancreatic ductal adenocarcinoma

CYP1B1:

Cytochrome P450 1B1

PAHs:

Polycyclic aromatic hydrocarbons

OR:

Odds ratio

CI:

Confidence interval

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Acknowledgments

Supported by research grants from Red temática de investigación cooperativa de centros en Cáncer (C03/10), Red temática de investigación cooperativa de centros en Epidemiología y salud pública (C03/09), and CIBER de epidemiología y salud pública, Instituto de Salud Carlos III, Ministry of Health, Madrid. The authors gratefully acknowledge scientific and technical assistance provided by David J. MacFarlane, Isabel Egea, Elisa Puigdomenech, and Silvia Geeraerd.

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Authors and Affiliations

  1. Institut Municipal d’Investigació Mèdica (IMIM), CIBER de Epidemiología y Salud Pública (CIBERESP), Carrer del Dr. Aiguader 88, 08003, Barcelona, Spain

    Marta Crous-Bou, Miquel Porta, José A. Pumarega, Tomàs López, Joan Alguacil, Eva Morales, Núria Malats & Francisco X. Real

  2. School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

    Marta Crous-Bou & Miquel Porta

  3. Harvard School of Public Health, Boston, MA, USA

    Immaculata De Vivo & David J. Hunter

  4. Channing Laboratory, Brigham and Women’s Hospital, Boston, MA, USA

    Immaculata De Vivo & David J. Hunter

  5. Department of Environmental Biology & Public Health, Universidad de Huelva, Huelva, Spain

    Joan Alguacil

  6. Hospital Son Dureta, Palma de Mallorca, Spain

    Juli Rifà

  7. Universitat Pompeu Fabra, Barcelona, Spain

    Francisco X. Real

Authors
  1. Marta Crous-Bou
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  2. Immaculata De Vivo
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  3. Miquel Porta
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  4. José A. Pumarega
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  5. Tomàs López
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  6. Joan Alguacil
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  7. Eva Morales
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  8. Núria Malats
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  9. Juli Rifà
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  10. David J. Hunter
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  11. Francisco X. Real
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For the PANKRAS II Study Group

Corresponding author

Correspondence to Miquel Porta.

Additional information

PANKRAS II study group—Members of the multicenter prospective study on the role of K-ras and other genetic alterations in the diagnosis, prognosis and etiology of pancreatic and biliary diseases (PANKRAS II) study group are mentioned in previous publications.

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Crous-Bou, M., De Vivo, I., Porta, M. et al. CYP1B1 Polymorphisms and K-ras Mutations in Patients with Pancreatic Ductal Adenocarcinoma. Dig Dis Sci 53, 1417–1421 (2008). https://doi.org/10.1007/s10620-008-0235-9

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  • DOI: https://doi.org/10.1007/s10620-008-0235-9

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