摘要
目的探讨鼠双微体．2（MDM2）基因rs2279744位点T—G多态与P53基因rsl042522位点G—c多态之间的交互作用与乳腺癌遗传易感性的关联。方法于2001年3月至2011年5月，选取杭州市余杭区女性乳腺癌患者600例作为病例组；选取同时期余杭区某医院参加健康体检的，年龄及地域分布与病例组匹配的健康女性600名作为对照组。采集研究对象静脉全血，并通过问卷收集其人口学资料。应用PCR－限制性片段长度多态（PCR—RFLP）法进行分型，应用logistic回归分析MDM2基因rs2279744位点T—G与P53基因rsl042522位点G—C多态性之间的交互作用与乳腺癌患病的影响。结果MDM2基因rs2279744位点GG、TG及TT基因型在病例组分布频率分别为31．5％（189／600）、45．5％（273／600）及23．0％（138／600）．在对照组中分别为19．0％（114／600）、49．2％（295／600）及31．8％（191／600）。P53基因rsl042522位点GG、GC及CC基因型在病例组分布频率分别为23．1％（139／600）、50．2％（301／600）及26．7％（160／600），在对照组中分别为30．5％（183／600）、51．3％（308／600）及18．2％（109／600）。回归分析显示，携带rs2279744位点TG、GG基因型能明媪提高乳腺癌的患病风险[OR（95％CI）值分别为：1．31（0．97～1．73）、2．24（1．61～3．09）]，携带rsl042522位点GC、CC基因型能明显提高乳腺癌的患病风险[OR（95％CI）值分别为：1．34（0．94～1．68）、1．89（1．35—2．68）]。两基因多态位点联合分析显示，与携带rs2279744位点rrr基因型和rsl042522位点GG基因型的个体相比[病例组和对照组中分布频率分别为4．8％（29／600）、11．5％（69／600）]，携带rs2279744位点TG或GG基因型和rsl042522位点GC或cc基因型[病例组和对照组中分布频率分别为95．2％（571／600）、88．5％（531／600）]能明显增加乳腺癌的患病风险（TG／GG＋GG：OR=2．30，95％CI：1．39—3．82；TT＋GC／CC：OR=2．14，95％CI：1．29～3．55：TG／GG＋GC／CC：OR=2．86，95％CI：1．80～4．53），即MDM2和P53基因的这两个多态位点联合交互作用能明显增加乳腺患病风险（P=0．046），当两位点均存在危险基因型时，乳腺癌的患病风险更大。结论MDM2基因rs2279744位点T—G多态和P53基因rsl042522位点G—c多态是乳腺癌患病的遗传易感因素，且两个位点的多态性之间的交互作用与乳腺癌遗传易感性相关。
Objective To investigate the combined effects between the two polymorphisms murine double minute 2 （MDM2） rs2279744 T→G and P53 rs1042522 G→C on the genetic susceptibility of breast cancer. Methods A total of 600 female patients with diagnosed breast cancer were consecutively recruited from the Yuhang district, Hangzhou city during March 2001 to May 2009. In the same period as the cases were collected,600 healthy women living in Yuhang district, Hangzhou city were selected from a nutritional survey conducted. Peripheral blood lymphocytes were obtained from the study subjects and the demographic information were collected through questionnaires. PCR-restrietion fragment length polymorphism （PCR-RFLP） was used for genotyping MDM2 rs2279744 T→G and P53 rs1042522 G→C. Logistic regression analysis was used to analyze the combined effects of the two poiymorphisms on breast cancer risk. Results The frequency of MDM2 rs2279744 GG, TG and TY genotypes were 31.5% （ 189/600 ） ,45.5% （273/600）, 23.0% （138/600） in case group and 19. 0% （114/600） ,49. 2% （295/600） ,31.8% （191/600） in control group. The frequency of P53 rs1042522 GG,GC and CC genotypes were 23.1% （139/600） ,50.2% （301/ 600） ,26.7% （160/600） in case group and 30. 5% （183/600） ,51.3% （308/600）, 18.2% （109/600） in control group. Logislie regression analysis showed that carriers with rs2279744 TG, GG genotypes had a significant increased risk for developing breast cancer compared with rs2279744 TT carriers （ OR = 1.31, 95% CI： O. 97 - 1.73 for TG; OR =2. 24,95% CI： 1.61 - 3.09 for GG）. When comparing with rsl042522 GG carriers,carriers with rs1042522 GC,CC genotypes had a significant increased risk for developing breast cancer （OR=1.34,95%C1：0.94-1.68 for GC; 0R=1.89,95%CI： 1.35-2.68 for CC）.The united analysis of this two polymorphisms showed that compared with individuals carrying rs2279744 TT and rs1042522 GG （the frequency were 4. 8% （29/600） in case group and 11.5% （69/600） in control group） , carries with rs2279744 TG/GG and rs1042522 GC/GG genotypes （the frequency were 95.2% （571/ 600） in case group and 88,5% （531/600） in control group） showed significant higher risk in the susceptibility to breast cancer （ OR = 2. 30,95% CI： 1.39 - 3.82 for TG/GC ＋ GG; OR = 2. 14,95% CI： 1.29 -3.55 for TT ＋ GC/CC; OR --2.86,95% CI： 1.80 -4.53 for TG/GG ＋ GC/CC）. The combination of MDM2 rs2279744 T--~G and P53 rs1042522 G--＋C contributed to a significantly higher risk of breast cancer than did any one of the variant （ P = 0. 046 ）. The risk of susceptibility to breast cancer was much higher when this two polymorphisms both variant. Conclusions The MDM2 rs2279744 T→G and P53 rs1042522 G→C may be risk factor for breast cancer. Significant combined effects between the two polymorphisms may contribute to the genetic susceptibility to breast cancer.
出处
《中华预防医学杂志》
CAS
CSCD
北大核心
2013年第2期124-128,共5页
Chinese Journal of Preventive Medicine
关键词
乳腺肿瘤
多态性
单核苷酸
疾病遗传易感性
基因
P53
Breast neoplasms
Polymorphism, single nucleotide
Genetic predisposition to disease
Genes,p53
