Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, 226014, UP, India.
J Cancer Res Clin Oncol. 2014 May;140(5):725-35. doi: 10.1007/s00432-014-1621-7. Epub 2014 Feb 21.
Gallbladder cancer (GBC), the most common gastrointestinal and biliary tract malignancy, often coincides with gallstone disease (GSD). The genetic variants of adrenergic receptor (ADR) have been previously reported to be associated with hypomotility disorder of cardiovascular system and GSD. Since GSD may function as GBC precursor, the present study aimed to investigate the association of common functional genetic variants of ADRA2A C-1291G, ADRβ3 T190C or Trp64Arg, and ADRβ1 C1165G or Arg389Gly with GBC and GSD susceptibility.
The present study included a total of 400 histologically confirmed GBC, 230 GSD, and 268 healthy controls. The ADRA2A C-1291G, ADRβ3 T190C, and ADRβ1 C1165G polymorphisms were determined by PCR-RFLP. Statistical analysis was performed by using SPSS version 16.
ADRβ3 T190C polymorphism was significantly associated with increased risk of GBC (CT: Pcorr = 0.015, OR 2.87; CC: Pcorr = 0.038, OR 10.33; C allele: Pcorr = 0.014, OR 2.7; CT + CC: Pcorr = 0.017, OR 3.05). These associations existed even after gallstone and gender stratification. Similarly, ADRβ3 T190C polymorphism was also associated with GSD risk, though limited only to female GSD patients. In contrary, ADRA2A C-1291G conferred a marginally increased risk only in GSD patients. ADRβ1 C1165G polymorphism was not associated with GBC and GSD susceptibility when compared to controls.
ADRβ3 T190C polymorphism is significantly associated with GBC and GSD susceptibility. The ADRβ3 T190C may be involved in the pathophysiology of GBC by both gallstone-dependent pathway and by some other independent mechanisms.
胆囊癌（GBC）是最常见的胃肠道和胆道恶性肿瘤，常与胆石病（GSD）同时发生。肾上腺素能受体（ADR）的遗传变异先前已被报道与心血管系统运动障碍和 GSD 有关。由于 GSD 可能作为 GBC 的前体，本研究旨在探讨 ADRA2A C-1291G、ADRβ3 T190C 或 Trp64Arg 和 ADRβ1 C1165G 或 Arg389Gly 的常见功能遗传变异与 GBC 和 GSD 易感性的关系。
本研究共纳入 400 例经组织学证实的 GBC、230 例 GSD 和 268 例健康对照。通过 PCR-RFLP 测定 ADRA2A C-1291G、ADRβ3 T190C 和 ADRβ1 C1165G 多态性。使用 SPSS 版本 16 进行统计分析。
ADRβ3 T190C 多态性与 GBC 风险增加显著相关（CT：Pcorr=0.015，OR 2.87；CC：Pcorr=0.038，OR 10.33；C 等位基因：Pcorr=0.014，OR 2.7；CT+CC：Pcorr=0.017，OR 3.05）。即使在进行胆结石和性别分层后，这些关联仍然存在。同样，ADRβ3 T190C 多态性也与 GSD 风险相关，但仅限于女性 GSD 患者。相反，ADRA2A C-1291G 仅在 GSD 患者中赋予了略微增加的风险。与对照组相比，ADRβ1 C1165G 多态性与 GBC 和 GSD 易感性无关。
ADRβ3 T190C 多态性与 GBC 和 GSD 易感性显著相关。ADRβ3 T190C 可能通过胆结石相关途径和其他一些独立机制参与 GBC 的病理生理学。
