Colorectal cancer susceptibility loci on chromosome 8q23.3 and 11q23.1 as modifiers for disease expression in lynch syndrome
Colorectal cancer susceptibility loci on chromosome 8q23.3 and 11q23.1 as modifiers for disease expression in lynch syndrome
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DOI：
10.1136/jmg.2010.079962
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发表时间：
2011-04-01
影响因子：
4
通讯作者：
Scott, Rodney J.
中科院分区：
文献类型：
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作者：
Talseth-Palmer, Bente A.;Brenne, Ingvild S.;Scott, Rodney J.
最近，研究人员鉴定了6个结直肠癌（CRC）易感位点，发现其中两个区域的两个单核苷酸多态性（snp） rs16892766 （8q23.3）和rs3802842 （11q23.1）与Lynch综合征患者CRC风险增加显著相关。本研究的目的是对这6个基因座中的9个snp进行基因分型，以证实先前的发现，并研究它们是否作为Lynch综合征患者疾病风险的修饰因子。患者队列包括来自298个澳大利亚和波兰家庭的684例Lynch综合征突变阳性患者。9个snp基因型分别为rs16892766 （8q23.3）、rs7014346和rs6983267 （8q24.21）、rs10795668 （10p14）、rs3802842 （11q23.1）、rs10318和rs4779584 （15q13.3）、rs4939827和rs4464148 （18q21.1）。对这些数据进行分析，以调查变异等位基因的存在与患病风险之间可能存在的关联。结果11q23.1染色体上的rs3802842和8q23.3染色体上的rs16892766 SNP与MLH1突变携带者发生结直肠癌的风险和诊断年龄存在相关性。携带SNP rs3802842纯合变异基因型的女性MLH1突变携带者发生结直肠癌的风险最高。当分析两个snp组合的风险等位基因的数量时，在携带三个风险等位基因的个体和不携带风险等位基因的个体之间发现了24年的差异。结论作者能够复制8q23.3和11q23染色体上的CRC易感位点与Lynch综合征患者发生CRC的风险之间的关联，但本研究仅在MLH1突变携带者中检测到这种关联。
Objective Recently, six colorectal cancer (CRC) susceptibility loci have been identified, and two single-nucleotide polymorphisms (SNPs)-rs16892766 (8q23.3) and rs3802842 (11q23.1)-from two of these regions have been found to be significantly associated with an increased CRC risk in patients with Lynch syndrome. The objective of this study was to genotype nine SNPs within these six loci to confirm previous findings and investigate whether they act as modifiers of disease risk in patients with Lynch syndrome.Design The patient cohort consisted of 684 mutation-positive patients with Lynch syndrome from 298 Australian and Polish families. Nine SNPs were genotyped: rs16892766 (8q23.3), rs7014346 and rs6983267 (8q24.21), rs10795668 (10p14), rs3802842 (11q23.1), rs10318 and rs4779584 (15q13.3), and rs4939827 and rs4464148 (18q21.1). The data were analysed to investigate possible associations between the presence of variant alleles and the risk of developing disease.Results An association between SNP rs3802842 on chromosome 11q23.1 and rs16892766 on chromosome 8q23.3 and the risk of developing CRC and age of diagnosis was found in MLH1 mutation carriers. Female MLH1 mutation carriers harbouring the homozygous variant genotype for SNP rs3802842 have the highest risk of developing CRC. When the number of risk alleles for the two SNPs combined was analysed, a difference of 24 years was detected between individuals carrying three risk alleles and those carrying no risk alleles.Conclusion The authors were able to replicate the association between the CRC susceptibility loci on chromosomes 8q23.3 and 11q23 and the risk of developing CRC in patients with Lynch syndrome, but the association could only be detected in MLH1 mutation carriers in this study.