Single nucleotide polymorphism in the ABCG8 transporter gene is associated with gallbladder cancer susceptibility.
BACKGROUND
Gallbladder cancer (GBC) usually arises against the background of gallstone disease, which may be causatively related to supersaturation of cholesterol in bile. An imbalance in cholesterol homeostasis because of oversecretion of cholesterol in the gallbladder promotes gallstone formation. The excretion of cholesterol from the liver is regulated by adenosine triphosphate-binding cassette transporter ABCG8. A common genetic polymorphism D19H of ABCG8 associated with gallstone disease may be causatively related to the genetic predisposition of GBC.


OBJECTIVE
We aimed to examine the role of ABCG8 D19H (rs11887534) polymorphism in susceptibility to GBC.


METHODS
This study included 171 confirmed GBC patients and 221 controls. Genotyping for the ABCG8 D19H polymorphism was performed by the polymerase chain reaction-restriction fragment length polymorphism method.


RESULTS
We observed that in our population the ABCG8 DH genotype frequency was significantly higher in GBC patients [P=0.011; odds ratio (OR)=1.79; 95% confidence interval (CI)=1.1-2.8]. Also, at the allele level, ABCG8H conferred an increased risk for GBC (P=0.023; OR=1.60; 95% CI=1.0-2.4). The risk was more pronounced in GBC patients with gallstones (P=0.027; OR=1.85; 95% CI=1.0-3.1), and in patients with an early onset of the disease (P=0.013; OR=2.55, 95% CI=1.2-5.3). However, there was no modulation of GBC risk because of the ABCG8 polymorphism in a gender-specific manner.


CONCLUSIONS
The results suggest that the DH genotype and the H allele of the ABCG8 D19H polymorphism are associated with GBC susceptibility. The GBC patients with gallstone disease harbouring the ABCG8 variant allele are at a higher risk, while the effect of this polymorphism on GBC patients without gallstones appears to be small.
Srivastava
Anvesha
A
Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India.
Tulsyan
Sonam
S
Pandey
Sachchida Nand
SN
Choudhuri
Gourdas
G
Mittal
Balraj
B
D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D005706:Gallbladder Neoplasms / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol