Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care.
Hum Mol Genet. 2013 Dec 15;22(24):5056-64. doi: 10.1093/hmg/ddt355. Epub 2013 Jul 29.
Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the "iCOGS" custom genotyping array. All ∼200 000 iCOGS variants were analysed with TL, and those displaying associations in healthy controls (n = 15 065) were further tested in breast cancer cases (n = 11 024). We found a novel TL association (Ptrend < 4 × 10(-10)) at 3p14.4 close to PXK and evidence (Ptrend < 7 × 10(-7)) for TL loci at 6p22.1 (ZNF311) and 20q11.2 (BCL2L1). We additionally confirmed (Ptrend < 5 × 10(-14)) the previously reported loci at 3q26.2 (TERC), 5p15.3 (TERT) and 10q24.3 (OBFC1) and found supportive evidence (Ptrend < 5 × 10(-4)) for the published loci at 2p16.2 (ACYP2), 4q32.2 (NAF1) and 20q13.3 (RTEL1). SNPs tagging these loci explain TL differences of up to 731 bp (corresponding to 18% of total TL in healthy individuals), however, they display little direct evidence for association with breast, ovarian or prostate cancer risks.
血液细胞的平均端粒长度（TL）是可遗传的，并且已经报道与多种疾病（包括癌症）的风险相关。我们对三个用于 TL 的 GWAS 进行了荟萃分析（总 n=2240），并通过“iCOGS”定制基因分型阵列选择了 1629 个变体进行复制。使用 TL 分析了所有约 200000 个 iCOGS 变体，并且在健康对照者（n=15065）中进一步测试了那些在乳腺癌病例（n=11024）中显示出关联的变体。我们在 3p14.4 附近发现了一个新的 TL 关联（Ptrend<4×10(-10)），靠近 PXK，并且在 6p22.1（ZNF311）和 20q11.2（BCL2L1）处发现了 TL 位点的证据（Ptrend<7×10(-7)）。我们还证实了（Ptrend<5×10(-14)）先前报道的 3q26.2（TERC）、5p15.3（TERT）和 10q24.3（OBFC1）处的位点，并且发现了对已发表的 2p16.2（ACYP2）、4q32.2（NAF1）和 20q13.3（RTEL1）处的位点的支持证据（Ptrend<5×10(-4)）。标记这些位点的 SNP 解释了高达 731bp 的 TL 差异（对应于健康个体中总 TL 的 18%），但是它们与乳腺癌、卵巢癌或前列腺癌风险的关联几乎没有直接证据。
