Xu Lixia, Zeng Zhirong, Chen Bin, Wu Xiaoqin, Yu Jun, Xue Ling, Tian Linwei, Wang Yiming, Chen Minhu, Sung Joseph J Y, Hu Pinjin
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou.
Oncol Lett. 2011 Mar;2(2):371-377. doi: 10.3892/ol.2011.249. Epub 2011 Jan 21.
The transforming growth factor-β (TGFβ) pathway plays an important role in various types of human cancer. However, the role of TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms in gastric cancer is controversial. We aimed to investigate the associations between these polymorphisms and gastric cancer susceptibility, clinicopathological parameters and survival. A case-control study was conducted in 1,010 gastric cancer patients and 1,500 healthy controls. Genotypes were determined by PCR-restriction fragment length polymorphism and DNA sequencing. Compared with the TT genotype, the TGFB1 -509 C allele (CT/CC) was significantly associated with a reduced risk of gastric cancer (OR, 0.71; 95% CI, 0.58-0.87; p=0.001) and certain subtypes of gastric cancer including intestinal type (OR, 0.70; 95% CI, 0.57-0.87; p=0.001), poorly differentiated (OR, 0.67; 95% CI, 0.54-0.85; p=0.001) and stage TNM III+IV (OR, 0.73; 95% CI, 0.58-0.92; p=0.008). Compared with the TGFBR2 -875 GG genotype, carriers of the A allele (AA/AG) had a significantly decreased gastric cancer risk (OR, 0.58; 95% CI, 0.62-0.91; P<0.001). A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles was associated with a further decreased risk of gastric cancer (OR, 0.42; 95% CI, 0.32-0.57, p<0.001). No significant correlation was observed between polymorphisms and survival of gastric cancer patients. Our results suggest that both the TGFB1 -509 and TGFBR2 -875 polymorphisms contribute to a decreased gastric cancer risk. The TGFB1 -509 polymorphism affects certain subtypes of gastric cancer according to clinicopathological parameters. A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles conferred a further decreased gastric cancer risk. These findings provide clues to the biological mechanisms that underline tumor heterogeneity.
转化生长因子-β（TGFβ）信号通路在各类人类癌症中发挥着重要作用。然而，TGFB1 -509C/T和TGFBR2 -875A/G基因多态性在胃癌中的作用仍存在争议。我们旨在研究这些基因多态性与胃癌易感性、临床病理参数及生存率之间的关联。我们对1010例胃癌患者和1500例健康对照进行了一项病例对照研究。通过聚合酶链反应-限制性片段长度多态性分析及DNA测序确定基因型。与TT基因型相比，TGFB1 -509 C等位基因（CT/CC）与胃癌风险降低显著相关（比值比[OR]，0.71；95%置信区间[CI]，0.58 - 0.87；P = 0.001），且与某些胃癌亚型相关，包括肠型（OR，0.70；95% CI，0.57 - 0.87；P = 0.001）、低分化型（OR，0.67；95% CI，0.54 - 0.85；P = 0.001）和TNM III+IV期（OR，0.73；95% CI，0.58 - 0.92；P = 0.008）。与TGFBR2 -875 GG基因型相比，A等位基因携带者（AA/AG）的胃癌风险显著降低（OR，0.58；95% CI，0.62 - 0.91；P < 0.001）。TGFB1 -509 C和TGFBR2 -875 A等位基因的组合与胃癌风险进一步降低相关（OR，0.42；95% CI，0.32 - 0.57，P < 0.001）。未观察到基因多态性与胃癌患者生存率之间存在显著相关性。我们的结果表明，TGFB1 -509和TGFBR2 -875基因多态性均与胃癌风险降低有关。TGFB1 -509基因多态性根据临床病理参数影响某些胃癌亚型。TGFB1 -509 C和TGFBR2 -875 A等位基因的组合使胃癌风险进一步降低。这些发现为肿瘤异质性的生物学机制提供了线索。
