Garre P, DE LA Hoya M, Iniesta P, Romera A, Llovet P, Gonzalez S, Perez-Segura P, Capella G, Diaz-Rubio E, Caldes T
Laboratorio de Oncología Molecular, Hospital Universitario San Carlos, Madrid;
Exp Ther Med. 2010 Sep;1(5):879-883. doi: 10.3892/etm.2010.125. Epub 2010 Jul 21.
The Yin-Yang haplotype is defined as two mismatched haplotypes (Yin and Yang) representing the majority of the existing haplotypes in a particular genomic region. The human adenomatous polyposis coli (APC) gene shows a Yin-Yang haplotype pattern accounting for 84% of all of the haplotypes existing in the Spanish population. Several association studies have been published regarding APC gene variants (SNPs and haplotypes) and colorectal cancer (CRC) risk. However, no studies concerning diplotype structure and CRC risk have been conducted. The aim of the present study was to investigate whether the APC Yin-Yang homozygote diplotype is over-represented in patients with sporadic CRC when compared to its distribution in controls, and its association with CRC risk. TaqMan(®) assays were used to genotype three tagSNPs selected across the APC Yin-Yang region. Frequencies of the APC Yin-Yang tagSNP alleles, haplotype and diplotype of 378 CRC cases and 642 controls were compared. Two Spanish CRC group samples were included [Hospital Clínico San Carlos in Madrid (HCSC) and Instituto Catalán de Oncología in Barcelona (ICO)]. Analysis of 157 consecutive CRC patients and 405 control subjects from HCSC showed a significative effect for the risk of CRC (OR=1.93; 95% CI 1.32-2.81; P=0.001). However, this effect was not confirmed in 221 CRC patients and 237 control subjects from ICO (OR=0.89; 95% CI 0.61-1.28; P=0.521). We found a significant association between the APC homozygote Yin-Yang diplotype and the risk of colorectal cancer in the HCSC samples. However, we did not observe this association in the ICO samples. These observations suggest that a study with a larger Spanish cohort is necessary to confirm the effects of the APC Yin-Yang diplotype on the risk of CRC.
阴阳单倍型被定义为两个不匹配的单倍型（阴和阳），它们代表了特定基因组区域中大多数现有的单倍型。人类腺瘤性息肉病（APC）基因呈现出阴阳单倍型模式，占西班牙人群中所有单倍型的84%。关于APC基因变体（单核苷酸多态性和单倍型）与结直肠癌（CRC）风险的多项关联研究已经发表。然而，尚未进行关于双倍型结构与CRC风险的研究。本研究的目的是调查与对照组相比，散发性CRC患者中APC阴阳纯合子双倍型是否过度出现，以及其与CRC风险的关联。采用TaqMan（®）检测对跨越APC阴阳区域选择的三个标签单核苷酸多态性进行基因分型。比较了378例CRC病例和642例对照的APC阴阳标签单核苷酸多态性等位基因、单倍型和双倍型的频率。纳入了两个西班牙CRC组样本[马德里的圣卡洛斯临床医院（HCSC）和巴塞罗那的加泰罗尼亚肿瘤研究所（ICO）]。对来自HCSC的157例连续CRC患者和405例对照受试者的分析显示，对CRC风险有显著影响（比值比=1.93；95%置信区间1.32 - 2.81；P = 0.001）。然而，在来自ICO的221例CRC患者和237例对照受试者中未证实这种影响（比值比=0.89；95%置信区间0.61 - 1.28；P = 0.521）。我们在HCSC样本中发现APC纯合子阴阳双倍型与结直肠癌风险之间存在显著关联。然而，我们在ICO样本中未观察到这种关联。这些观察结果表明，需要进行一项更大规模的西班牙队列研究来证实APC阴阳双倍型对CRC风险的影响。
