Houlston R S, Tomlinson I P
Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
Gastroenterology. 2001 Aug;121(2):282-301. doi: 10.1053/gast.2001.26265.
BACKGROUND & AIMS: Increasingly, studies of the relationship between common genetic variants and colorectal tumor risk are being proposed. To assess the evidence that any of these confers a risk, a systematic review and meta-analysis of published studies was undertaken.
Fifty studies of the effect of common alleles of 13 genes on risk were identified. To clarify the impact of individual polymorphisms on risk, pooled analyses were performed.
Of the 50 studies identified, significant associations were seen in 16, but only 3 were reported in more than one study. Pooling studies, significant associations were only seen for 3 of the polymorphisms: adenomatosis polyposis coli (APC)-I1307K (odds ratio [OR] = 1.58, 95% confidence interval [CI]: 1.21-2.07); Harvey ras-1 variable number tandem repeat polymorphism (HRAS1-VNTR; OR = 2.50, 95% CI: 1.54-4.05); and methylenetetrahydrofolate reductase (MTHFR)(Val/Val) (OR = 0.76, 95% CI: 0.62-0.92). For tumor protein 53 (TP53), N-acetyl transferase 1 (NAT1), NAT2, glutathione-S transferase Mu (GSTM1), glutathione-S transferase Theta (GSTT1), and glutathione-S transferase Pi (GSTP1) polymorphisms, the best estimates are sufficient to exclude a 1.7-fold increase in risk of colorectal cancer.
APC-I1307K, HRAS1-VNTR, and MTHFR variants represent the strongest candidates for low penetrance susceptibility alleles identified to date. Although their genotypic risks are modest, their high frequency in the population implies that they may well have considerable impact on colorectal cancer incidence. Determining precise risk estimates associated with other variants and gene-gene and gene-environment interactions will be contingent on further studies with sample sizes larger than typically used to date.
越来越多关于常见基因变异与结直肠肿瘤风险之间关系的研究被提出。为评估这些变异中任何一种是否会带来风险，我们对已发表的研究进行了系统综述和荟萃分析。
我们确定了50项关于13个基因的常见等位基因对风险影响的研究。为阐明个体多态性对风险的影响，我们进行了汇总分析。
在确定的50项研究中，16项发现了显著关联，但只有3项在不止一项研究中被报道。汇总研究中，仅3种多态性存在显著关联：腺瘤性息肉病 coli（APC）-I1307K（优势比[OR]=1.5（此处原文有误，应为1.58），95%置信区间[CI]：）；哈维 ras-1可变数目串联重复多态性（HRAS1-VNTR；OR = 2.50，95% CI：1.54-4.05）；以及亚甲基四氢叶酸还原酶（MTHFR）（Val/Val）（OR = 0.76，95% CI：0.62-0.92）。对于肿瘤蛋白53（TP53）、N-乙酰转移酶1（NAT1）、NAT2、谷胱甘肽-S转移酶Mu（GSTM1）、谷胱甘肽-S转移酶Theta（GSTT1）和谷胱甘肽-S转移酶Pi（GSTP1）多态性，最佳估计足以排除结直肠癌风险增加1.7倍。
APC-I1307K、HRAS1-VNTR和MTHFR变异是迄今为止确定的低外显率易感性等位基因的最强候选者。尽管它们的基因型风险不大，但在人群中的高频率意味着它们很可能对结直肠癌发病率有相当大的影响。确定与其他变异以及基因-基因和基因-环境相互作用相关的精确风险估计将取决于样本量比目前通常使用的更大的进一步研究。 （备注：原文中“95% confidence interval [CI]: 1.21-2.07”在结果部分翻译中遗漏，已补充完整）
