Association of genetic variants of xenobiotic and estrogen metabolism pathway (CYP1A1 and CYP1B1) with gallbladder cancer susceptibility.

[carcinoma of the gallbladder]

Gallbladder carcinoma is a highly aggressive cancer with female predominance . Interindividual differences in the effectiveness of the activation /detoxification of environmental carcinogens and endogenous estrogens may play a crucial role in cancer susceptibility . The present study included 410 patients with carcinoma of the gallbladder (GBC ) and 230 healthy subjects . This study examined association of CYP 1 A 1 -MspI , CYP 1 A 1 -Ile 462 Val , and CYP 1 B 1 -Val 432 Leu with GBC susceptibility . CYP 1 A 1 -MspI [CC ] and CYP 1 A 1 -Ile 462 Val [iso /val ] genotypes were found to be significantly associated with GBC (p =0 .006 and p =0 .03 , respectively ), as compared to healthy controls , while CYP 1 B 1 -Val 432 Leu was not associated with GBC . The CYP 1 A 1 haplotype [C-val ] showed a significant association with GBC (p =0 .006 ). On stratification based on gender , the CYP 1 A 1 -MspI [CC ] genotype showed an increased risk of GBC in females (p =0 .018 ). In case-only analysis , tobacco users with CYP 1 A 1 -MspI [CT ] genotypes were at a higher risk of GBC (p =0 .008 ). Subdividing the GBC patients on the basis of gallstone status , the CYP 1 A 1 haplotype [C-val ] imparted a higher risk in patients without stones when compared to controls (p =0 .001 ). The results remained significant even after applying Bonferroni correction . Multivariate analysis revealed an increased risk of CYP 1 A 1 iso /val and val /val genotypes in GBC patients having BMI >25 (p =0 .021 ). The CYP 1 A 1 polymorphisms may confer increased risk of GBC , probably due to impaired xenobiotic or hormone metabolism through a gallstone-independent pathway .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated