Lipoprotein receptor associated protein (LRPAP1) insertion/deletion polymorphism: association with gallbladder cancer susceptibility.

Background: Low-density lipoprotein receptor-related protein associated protein (LRPAP1) insertion/deletion polymorphism influences cholesterol homeostasis and may confer risk for gallstone disease and gallbladder carcinoma (GBC) incidence usually parallels with the prevalence of cholelithiosis.

Aim: We aimed to examine the role of LRPAP1 polymorphism in susceptibility to GBC.

Methods: Present case control study included 129 proven GBC patients, 183 gallstone patients, and 208 healthy controls. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method.

Results: The D allele of LRPAP1 was significantly higher in GBC patients as compared to gallstone patients (p = 0.013; OR = 1.6, 95% CI = 1.1-2.4). However, II genotype and I allele was associated with reduced risk of GBC as compared to gallstone patients (p = 0.002; OR = 0.1, 95% CI = 0.1-0.6; p = 0.013; OR = 0.6, 95% CI = 0.4-0.8) The increased risk due to D allele was limited to female GBC patients (p = 0.021; OR = 1.8, 95% CI = 1.1-3.0). However, reduced risk due to II genotype and I allele was observed which was also confined to female GBC patients (p = 0.005; OR = 0.1, 95% CI = 0.1-0.6; p = 0.021; OR = 0.5, 95% CI = 0.3-0.8). On comparing GBC patients having gallstone with gallstone patients, high risk was observed in the GBC patients having gallstone due to the presence of D allele (p = 0.032; OR = 1.7, 95% CI = 1.0-2.8). However, low risk was observed because of I allele in GBC patients with gallstone in comparison to gallstone patients (p = 0.032, OR = 0.6, 95% CI = 0.4-0.9).

Conclusion: It appears that 'D' allele may modulate the susceptibility of GBC, and the risk is independent to genetic risk of gallstone.