Srivastava A, Pandey S N, Choudhuri G, Mittal B
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, UP, India.
Scand J Immunol. 2008 May;67(5):516-22. doi: 10.1111/j.1365-3083.2008.02097.x.
Inflammation of gallbladder is an established risk factor for gallbladder cancer (GBC) pathogenesis. Chemokine receptors play crucial role in antitumour immunity and are involved in inflammation and pathogenesis of cancers. Present study was aimed to examine the role of CCR5 Delta32 polymorphism in conferring genetic susceptibility to GBC. Present case-control study included 144 proven GBC patients and 210 healthy controls. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistically significant difference was observed in distribution of CCR5+/Delta32 genotype (P = 0.028) [odds ratio (OR) = 2.850; 95% confidence interval (CI) = 1.1-7.2] and CCR5 Delta32 allele (P = 0.012) (OR = 3.145, 95% CI = 1.2-7.7) in GBC patients which was conferring high risk. Stratification of GBC patients showed significant association of CCR5+/Delta32 genotype and CCR5 Delta32 allele with GBC patients with and without gallstones. Analysis based on age of onset and gender suggested significant association of CCR5 Delta32 allele with early onset (<50 years) of the disease but only marginal influence of gender in CCR5 Delta32-mediated risk of cancer. Risk was further modulated by tobacco usage and significantly increased risk was observed in tobacco users with CCR5+/Delta32 genotype. In conclusion, CCR5+/Delta32 genotype and CCR5 Delta32 allele confer significant risk for GBC particularly in patients with early onset and tobacco usage. Role of CCR5+/Delta32 polymorphism in GBC susceptibility is independent of gallstone formation.
胆囊炎症是胆囊癌(GBC)发病机制中已确定的危险因素。趋化因子受体在抗肿瘤免疫中起关键作用,并参与癌症的炎症和发病机制。本研究旨在探讨CCR5 Delta32多态性在赋予GBC遗传易感性中的作用。本病例对照研究纳入了144例经证实的GBC患者和210例健康对照。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行基因分型。在GBC患者中,CCR5+/Delta32基因型(P = 0.028)[比值比(OR)= 2.850;95%置信区间(CI)= 1.1 - 7.2]和CCR5 Delta32等位基因(P = 0.012)(OR = 3.145,95% CI = 1.2 - 7.7)的分布存在统计学显著差异,这赋予了较高风险。GBC患者分层显示,CCR5+/Delta32基因型和CCR5 Delta32等位基因与有或无胆结石的GBC患者均有显著关联。基于发病年龄和性别的分析表明,CCR5 Delta32等位基因与疾病早发(<50岁)显著相关,但性别在CCR5 Delta32介导的癌症风险中仅有微弱影响。风险因吸烟而进一步调节,在具有CCR5+/Delta32基因型的吸烟者中观察到风险显著增加。总之,CCR5+/Delta32基因型和CCR5 Delta32等位基因赋予GBC显著风险,特别是在早发患者和吸烟者中。CCR5+/Delta32多态性在GBC易感性中的作用独立于胆结石形成。