Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Br J Cancer. 2012 Sep 4;107(6):1001-8. doi: 10.1038/bjc.2012.329. Epub 2012 Aug 9.
Polymorphic variation at the 5p15.33 (TERT-CLPTM1L) locus is associated with the risk of many cancers but a relationship with colorectal cancer (CRC) risk has yet to be defined.
We used data from six genome-wide association studies (GWAS) of CRC, linkage disequilibrium mapping and imputation, to examine the relationship between 73 single-nucleotide polymorphisms at 5p15.33 and CRC risk in detail.
rs2736100, which localises to intron 2 of TERT, provided the strongest evidence of an association with CRC (P=2.28 × 10⁻⁴). The association was also shown in an independent series of 10 047 CRC cases and 6918 controls (P=0.02). A meta-analysis of all seven studies (totalling 16 039 cases, 16 430 controls) provided increased evidence of association (P=2.49 × 10⁻⁵; per allele odds ratio=1.07). The association of rs2736100 on CRC risk was shown to be independent of 15 low-penetrance variants previously identified.
The rs2736100 association demonstrates an influence of variation at 5p15.33 on CRC risk and further evidence that the 5p15.33 (TERT-CLPTM1L) locus has pleiotropic effects (reflecting generic or lineage-specific effects) on cancer risk.
5p15.33（TERT-CLPTM1L）基因座的多态性变异与多种癌症的风险相关，但与结直肠癌（CRC）风险的关系尚未确定。
我们使用了六项 CRC 全基因组关联研究（GWAS）、连锁不平衡图谱和单核苷酸多态性（SNP）的推断数据，详细研究了 5p15.33 上的 73 个 SNP 与 CRC 风险之间的关系。
rs2736100 位于 TERT 基因的内含子 2，为与 CRC 风险相关的最强证据（P=2.28×10⁻⁴）。在另一项包含 10047 例 CRC 病例和 6918 例对照的独立系列研究中也观察到了这种相关性（P=0.02）。对所有 7 项研究（总计 16039 例病例，16030 例对照）的荟萃分析提供了更强的相关性证据（P=2.49×10⁻⁵；每个等位基因的比值比=1.07）。rs2736100 与 CRC 风险的相关性表明，它独立于先前确定的 15 种低外显率变异。
rs2736100 的相关性表明 5p15.33 上的变异对 CRC 风险有影响，进一步证明了 5p15.33（TERT-CLPTM1L）基因座对癌症风险具有多效性（反映了一般或谱系特异性效应）。
