Background As a model for both multistep and multipathway carcinogenesis, colorectal neoplastic progression provides paradigms for researching both oncogenes and tumor suppressor genes （TSGs）. However, the mechanism of colorectal cancer （CRC） is not completely understood, and many genes may be involved in the colorectal carcinogenesis. The purpose of this study was to screen for the potential TSGs on chromosome 1q31.1-32.1 in Chinese patients with sporadic colorectal cancer, to explore whether colorectal cancer in the Chinese population has unique genetic alterations and determine whether other putative TSGs exist and contribute to colon carcinogenesis. Methods Six polymorphic microsatellite markers, at a density of approximately one marker in every 1.6 cM, were chosen for refined loss of heterozygosity （LOH） mapping of 1q31.1-32.1. Eighty-three colorectal cancer patients＇ tumor and normal DNA were analyzed via polymerase chain reaction （PCR） for these microsatellite markers. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. On the basis of refined LOH mapping results, we undertook a microarray-based expression screening to identify tumor association genes in 19 of the CRC cases. Results The average LOH frequency of 1q31.1-32.1 was 24.41%, with the highest frequency of 36.73% （18/49） at D1S2622, and the lowest of 16.42% （11/67） at D1S412. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622. There was no significant association between LOH of any marker in the studied regions and the clinicopathological data （patient sex, age, tumor size, growth pattern, or Dukes stage）. On the basis of refined mapping results, we chose 25 genes located in the D1S413-D1S2622 （1q31.3-32.1） region and presented a microarray-based high throughput screening approach in 19 sporadic CRC cases to identify candidate CRC related tumor suppressor genes. This study found 4
目的检测单核苷酸多态性(SNP)位点Arg399Gln在散发性结直肠癌患者和非癌对照组中的分布情况,分析其与散发性结直肠癌及其临床病理特征的相关性。方法从178例肿瘤组织和非癌对照组的180例血样中提取DNA,采用Taqman探针技术检测Arg399Gln多态性表型,并用统计软件计算各基因型的比值比(OR)和95%可信区间(95%CI)。结果肿瘤组与对照组就XRCC1 Arg399Gln多态性的基因表型差异有统计学意义(P<0.05);年龄不超过60岁的患者和超过60岁的患者在该位点的基因型差异有统计学意义(P<0.05);以399Arg/Arg基因型为参照,在年龄超过50岁的人群中(OR=0.64,95% CI 0.50～0.83,P<0.05)和男性人群中(OR=0.64,95% CI 0.51～0.79,P<0.05)携带至少一个Gln等位基因可致罹患散发性结直肠癌的风险显著降低;XRCC1 399SNP与患者性别及散发性结直肠癌的发生部位、Dukes分期、浸润深度、淋巴结转移以及病理分型均无显著相关性(P均>0.05)。结论XRCC1 399SNP可能通过改变DNA的损伤修复功能,成为散发性结直肠癌的易感因素。
