CAJ | 학술논문

目的探讨p53 72 Arg→Pro和鼠双微体同源基因2(MDM2) 309 T→G多态与结直肠癌(CRC)发生发展的关系.方法采用病例-对照关联研究方法,分析1000例CRC和1300例正常对照中p53 72 Arg→Pro和MDM2 309 T→G的基因型.以多因素Logistic回归模型计算各基因型的比值比(OR)及其95%可信区间(CI).结果携带MDM2 309 GG或TG基因型者患CRC的风险比TT基因型者显著增高,OR分别为2.06(95%CI为1.62～2.62)和1.31(95%CI为1.06～1.62).p53 72 Arg→Pro多态与CRC风险不相关.两个基因多态联合分析表明,既携带MDM2 309 GG,又携带p53 72 Pro/Pro基因型者,患CRC的OR显著高于携带MDM2 309 TT和p53 72 Pro/Pro基因型者[2.75(95%CI为1.60～4.70)比1.09(95%CI为0.63～1.88);χ2=9.83,P=0.002].结论 MDM2基因的遗传多态可能是CRC的遗传易感性因素.
목적 탐토p53 72 Arg→Pro화서쌍미체동원기인2(MDM2) 309 T→G다태여결직장암(CRC)발생발전적관계.방법 채용병례-대조관련연구방법,분석1000례CRC화1300례정상대조중p53 72 Arg→Pro화MDM2 309 T→G적기인형.이다인소Logistic회귀모형계산각기인형적비치비(OR)급기95%가신구간(CI).결과 휴대MDM2 309 GG혹TG기인형자환CRC적풍험비TT기인형자현저증고,OR분별위2.06(95%CI위1.62～2.62)화1.31(95%CI위1.06～1.62).p53 72 Arg→Pro다태여CRC풍험불상관.량개기인다태연합분석표명,기휴대MDM2 309 GG,우휴대p53 72 Pro/Pro기인형자,환CRC적OR현저고우휴대MDM2 309 TT화p53 72 Pro/Pro기인형자[2.75(95%CI위1.60～4.70)비1.09(95%CI위0.63～1.88);χ2=9.83,P=0.002].결론 MDM2기인적유전다태가능시CRC적유전역감성인소.
Objective The tumor suppressor p53 pathway plays a crucial role in preventing carcinogenesis through its ability to impose cell cycle arrest and apoptosis following DNA damage or oncogene activation. Mouse double minute 2 (MDM2) gene is a key negative regulator of p53 pathway and overexpressed in many cancers as oncoprotein. We have previously shown that genetic polymorphisms in the MDM2 promoter (309T→G) and p53 coding region (72Arg→Pro) are associated with susceptibility to esophageal and lung cancers. This study investigated the associations between these polymorphisms in p53 and MDM2 and risk of the occurrence and progression of colorectal cancer. Methods Genotypes of 1000 Chinese colorectal cancer patients and 1300 controls were determined by PCR-based restriction fragment length polymorphism or tetra-primer amplification refractory mutation system-PCR. Associations with risk of colorectal cancer were estimated by unconditional logistic regression. Results An increased colorectal cancer risk associated with the MDM2 GG [odds ratio (OR)=2.06,95% confidence interval (CI)=1.62-2.62] or TG (OR=1.31,95%CI=1.06-1.62) genotype was observed compared with the TT genotype. No association was found between p53 polymorphism and risk of the cancer, with the ORs being 0.87 (95%CI=0.68-1.11) for the Pro/Pro and 0.85 (95%CI=0.70-1.04) for the Arg/Pro genotype compared with the Arg/Arg genotype. However, combined analysis of MDM2 and p53 polymorphisms showed that compared with subjects carrying both MDM2 TT and p53 Arg/Arg genotypes, the OR for subjects carrying both MDM2 GG and p53 Pro/Pro genotypes was 2.75 (95%CI=1.60-4.70), significantly higher than that for subjects carrying both MDM2 TT and p53 Pro/Pro genotypes (OR=1.09,95%CI=0.63-1.88). Conclusion These results suggest that genetic polymorphism in MDM2 may be associated with susceptibility to colorectal cancer in a Chinese population.