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

• Published in: Digestive diseases and sciences Vol. 53; no. 5; pp. 1417 - 1421
• Main Authors: Crous-Bou, Marta, De Vivo, Immaculata, Porta, Miquel, Pumarega, José A., López, Tomàs, Alguacil, Joan, Morales, Eva, Malats, Núria, Rifà, Juli, Hunter, David J., Real, Francisco X.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-05-2008; Springer; Springer Nature B.V
• Subjects: Adenocarcinoma - genetics; Alleles; Aryl Hydrocarbon Hydroxylases - genetics; Biochemistry; Biological and medical sciences; Cytochrome P-450 CYP1B1; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Genes, ras; Genotype; Hepatology; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Logistic Models; Male; Medical sciences; Medicine; Medicine & Public Health; Mutation - genetics; Oncology; Original Paper; Pancreatic Ducts - pathology; Pancreatic Neoplasms - genetics; Polymorphism, Genetic; Prospective Studies; Spain; Transplant Surgery; Tumors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Spain; K; CYP1B1 polymorphisms; oncogene; ras genes; Pancreatic neoplasms; Human; Metabolic diseases; Pancreas ductal adenocarcinoma; Malignant tumor; CYP1B1 polymorphisms .K-ras oncogene .ras genes; Pancreas cancer; Gastroenterology; Digestive diseases; Mutation; Onc gene; Ras gene; Cancer; Pancreatic disease; Polymorphism
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-008-0235-9

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.