Skoglund Johanna, Song Bo, Dalén Johan, Dedorson Stefan, Edler David, Hjern Fredrik, Holm Jörn, Lenander Claes, Lindforss Ulrik, Lundqvist Nils, Olivecrona Hans, Olsson Louise, Påhlman Lars, Rutegård Jörgen, Smedh Kennet, Törnqvist Anders, Houlston Richard S, Lindblom Annika
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Clin Cancer Res. 2007 Jun 15;13(12):3748-52. doi: 10.1158/1078-0432.CCR-06-2865.
Recently a common variant of the TGFBR1 gene, TGFBR16A, has been proposed to act as a low-penetrance tumor susceptibility allele for colorectal cancer, but data from published studies with individually low statistical power are conflicting. To further evaluate the relationship between TGFBR16A and colorectal cancer risk, we have conducted a large case-control study and a meta-analysis of previously published studies.
A total of 1,042 colorectal cancer cases and 856 population controls were genotyped for the TGFBR16A polymorphism. Previously published case-control studies of the relationship between TGFBR16A and colorectal cancer were identified, and a meta-analysis was conducted.
We found no evidence that homozygosity, heterozygosity or carrier status for the TGFBR16A allele confers an increased risk of colorectal cancer; respective odds ratios (OR) were 1.05 [95% confidence interval (95% CI), 0.83-1.32], 0.82 (95% CI, 0.34-1.99), and 0.92 (95% CI, 0.74-1.15), respectively. A meta-analysis of our case-control study and seven other studies that provided data on 2,627 colorectal cancer cases and 3,387 controls also yielded no evidence that possession of the TGFBR16A allele is associated with an elevated risk of colorectal cancer; pooled estimate of the OR were 1.20 (95% CI, 0.64-2.24) for homozygosity, 1.11 (95% CI, 0.96-1.29) for heterozygosity, and 1.13 (95% CI, 0.98-1.30) for carriers of TGFBR1*6A.
Current data provide limited support for the hypothesis that sequence variation in TGFBR1 defined by the TGFBR1*6A allele confers an elevated risk of colorectal cancer.
最近，有人提出转化生长因子β受体1（TGFBR1）基因的一个常见变体TGFBR16A作为一种低外显率的结直肠癌肿瘤易感性等位基因，但已发表的统计效力较低的研究数据相互矛盾。为了进一步评估TGFBR16A与结直肠癌风险之间的关系，我们开展了一项大型病例对照研究并对之前发表的研究进行了荟萃分析。
对1042例结直肠癌病例和856名人群对照进行TGFBR16A多态性基因分型。检索之前发表的关于TGFBR16A与结直肠癌关系的病例对照研究，并进行荟萃分析。
我们没有发现证据表明TGFBR16A等位基因的纯合性、杂合性或携带状态会增加患结直肠癌的风险；各自的比值比（OR）分别为1.05[95%置信区间（95%CI），0.83 - 1.32]、0.82（95%CI，0.34 - 1.99）和0.92（95%CI，0.74 - 1.15）。对我们的病例对照研究和其他七项研究（提供了2627例结直肠癌病例和3387名对照的数据）进行的荟萃分析也没有发现证据表明携带TGFBR16A等位基因与结直肠癌风险升高有关；TGFBR1*6A纯合性的OR合并估计值为1.20（95%CI，0.64 - 2.24），杂合性为1.11（95%CI，0.96 - 1.29），携带者为1.13（95%CI，0.98 - 1.30）。
目前的数据对TGFBR1*6A等位基因所定义的TGFBR1序列变异会增加结直肠癌风险这一假说提供了有限的支持。
