• 1.蘭州大學(xué)臨床醫(yī)學(xué)院（蘭州730000）;;
  • 2.蘭州大學(xué)第一醫(yī)院普外二科（蘭州730000）;;
  • 3.蘭州大學(xué)第一醫(yī)院腫瘤研究所（蘭州730000）;;
  • 4.蘭州大學(xué)第一醫(yī)院手術(shù)室（蘭州730000）;

目的 探討p53基因第72位密碼子(Arg72Pro)多態(tài)性與胃癌高發(fā)區(qū)甘肅河西地區(qū)漢族人群胃癌遺傳易感性的關(guān)系，并探討Arg72Pro多態(tài)性與環(huán)境因素、胃癌發(fā)生部位、病理分型等的相互關(guān)系。
方法 采用 Taq Man實時熒光定量PCR方法檢測140例胃癌患者、110例胃癌癌前病變患者以及125例健康人群的外周血標(biāo)本p53基因Arg72Pro的多態(tài)性，并比較其不同的基因型與胃癌風(fēng)險的關(guān)系； 對胃鏡活檢以及手術(shù)切除標(biāo)本應(yīng)用Warthin-Starry法(W-S法)判斷幽門螺桿菌（Hp）感染情況。
結(jié)果 胃癌組、癌前病變組及健康對照組的Pro等位基因頻率分別為 0.543、 0.482和0.472，Pro基因型攜帶者的胃癌發(fā)病風(fēng)險是Arg/Arg基因型攜帶者的1.846倍〔95% CI (1.006~3.387)， P =0.046〕。經(jīng)Logistic回歸篩選確定了飲食、Hp感染、精神因素以及腫瘤家族史為胃癌的危險因素，并與Pro基因型具有加乘作用。p53基因型分布和胃癌的部位及病理分型具有相關(guān)性（ P ＜ 0.05） 。
結(jié)論 p53 Arg72Pro多態(tài)性與甘肅河西地區(qū)漢族人群胃癌遺傳易感性相關(guān)，值得進(jìn)一步進(jìn)行功能學(xué)探討及大樣本人群驗證。

引用本文： 單勇,李玉民,李汛,周文策,石斌,何明彥,朱克祥,何建宏,劉濤,何文婷,俸鐵嵐. 甘肅胃癌高發(fā)區(qū)人群p53基因Arg72Pro多態(tài)性的初步研究. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(1): 12-17. doi: 復(fù)制

1. 李玉民， 石斌， 柴琛， 等. 甘肅省河西地區(qū)胃癌發(fā)病狀況的調(diào)查 [Ｊ] . 中華普通外科雜志， 2004； 19(3)： 183.
2. 張毅. 抑癌基因失活在多原發(fā)性惡性腫瘤發(fā)生中的意義 [Ｊ] . 中國普外基礎(chǔ)與臨床雜志， 2000； 7(6)： 418.
3. Mendoza-Rodríguez CA, Cerbón MA. Tumor suppressor gene p53: mechanisms of action in cell proliferation and death [Ｊ] . Rev Invest Clin, 2001; 53(3)： 266.
4. 趙仲堂主編. 流行病學(xué)研究方法與應(yīng)用 [Ｍ] . 第1版. 北京: 科學(xué)出版社， 2000： 523～542.
5. 朱新勇， 張同全， 王福春， 等. p53、 bcl-2和nm23基因在胃癌組織中的表達(dá)及其臨床意義 [Ｊ] . 中國普外基礎(chǔ)與臨床雜志， 2003; 10(6)： 589.
6. Feng Z, Hu W, Teresky AK, et al . Declining p53 function in the aging process: a possible mechanism for the increased tumor incidence in older populations [Ｊ] . Proc Nat Acad Sci, 2007; 104（42）： 16633.
7. Ventura A, Kirsch DG, McLaughlin ME, et al . Restoration of p53 function leads to tumour regression in vivo [Ｊ] . Nature, 2007; 445（7128）： 661.
8. Hu Y, McDermott MP, Ahrendt SA. The p53 codon 72 proline allele is associated with p53 gene mutations in non-small cell lung cancer [Ｊ] . Clin Cancer Res, 2005; 11(7)： 2502.
9. Han JY, Lee GK, Jang DH, et al . Association of p53 codon 72 polymorphism and MDM2 SNP309 with clinical outcome of advanced nonsmall cell lung cancer [Ｊ] . Cancer, 2008; 113(4) ∶799.
10. Lee JM, Shun CT, Wu MT, et al . The associations of p53 overexpression with p53 codon 72 genetic polymorphism in esophageal cancer [Ｊ] . Mutat Res, 2006; 594(1-2)：181.
11. Zhu ZZ, Cong WM, Liu SF, et al . Homozygosity for Pro of p53 Arg72Pro as a potential risk factor for hepatocellular carcinoma in Chinese population [Ｊ] . World J Gastroenterol, 2005; 11(2)：289.
12. Yoon YJ, Chang HY, Ahn SH, et al . MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection [Ｊ] . Carcinogenesis, 2008; 29(6)： 1192.
13. Santos AM, Sousa H, Pinto D, et al . Linking TP53 codon 72 and P21 nt590 genotypes to the development of cervical and ovarian cancer [Ｊ] . Eur J Cancer, 2006; 42(7)： 958.
14. Damin AP, Frazzon AP, Damin DC, et al . Evidence for an association of TP53 codon 72 polymorphism with breast cancer risk [Ｊ] . Cancer Detect Prev, 2006; 30(6)：523.
15. Gochhait S, Bukhari SI, Bairwa N, et al . Implication of BRCA 2-26G ＞A 5′ untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by p53 codon 72 Arg＞Pro polymorphism [Ｊ] . Breast Cancer Res, 2007; 9(5) ∶R71.
16. Jones JS, Chi X, Gu X, et al . p53 polymorphism and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population [Ｊ] . Clin Cancer Res, 2004; 10(17)：5845.
17. Crew KD, Neugut AI. Epiclemiology of upper gastrointestinal malignancies [Ｊ] . Semin Oncol, 2004; 31(4)：450.
18. Forman D, Newell DG, Fullerton F, et al . Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation [Ｊ] . BMJ, 1991; 302（6788）：1302.
19. Mitsuhashi J, Mitomi H, Tanabe S, et al . Differences in clinicopathological findings, cell kinetics and p53 expression between early gastric cancers with and without Helicobacter pylori infection [Ｊ] . Hepatogastroenterology, 2004; 51(60)：1636.
20. Wang J, Chi DS, Kalin GB, et al . Helicobacter pylori infection and oncogene expressions in gastric carcinoma and its precursor lesions [Ｊ] . Dig Dis Sci, 2002; 47(1)：107.
21. 童明宏， 孫晨光. 幽門螺桿菌感染、 p53基因突變與胃癌的相關(guān)性研究 [Ｊ] . 實用腫瘤雜志， 2003; 18(5)：393.
  1. 1. 李玉民， 石斌， 柴琛， 等. 甘肅省河西地區(qū)胃癌發(fā)病狀況的調(diào)查 [Ｊ] . 中華普通外科雜志， 2004； 19(3)： 183.
  2. 2. 張毅. 抑癌基因失活在多原發(fā)性惡性腫瘤發(fā)生中的意義 [Ｊ] . 中國普外基礎(chǔ)與臨床雜志， 2000； 7(6)： 418.
  3. 3. Mendoza-Rodríguez CA, Cerbón MA. Tumor suppressor gene p53: mechanisms of action in cell proliferation and death [Ｊ] . Rev Invest Clin, 2001; 53(3)： 266.
  4. 4. 趙仲堂主編. 流行病學(xué)研究方法與應(yīng)用 [Ｍ] . 第1版. 北京: 科學(xué)出版社， 2000： 523～542.
  5. 5. 朱新勇， 張同全， 王福春， 等. p53、 bcl-2和nm23基因在胃癌組織中的表達(dá)及其臨床意義 [Ｊ] . 中國普外基礎(chǔ)與臨床雜志， 2003; 10(6)： 589.
  6. 6. Feng Z, Hu W, Teresky AK, et al . Declining p53 function in the aging process: a possible mechanism for the increased tumor incidence in older populations [Ｊ] . Proc Nat Acad Sci, 2007; 104（42）： 16633.
  7. 7. Ventura A, Kirsch DG, McLaughlin ME, et al . Restoration of p53 function leads to tumour regression in vivo [Ｊ] . Nature, 2007; 445（7128）： 661.
  8. 8. Hu Y, McDermott MP, Ahrendt SA. The p53 codon 72 proline allele is associated with p53 gene mutations in non-small cell lung cancer [Ｊ] . Clin Cancer Res, 2005; 11(7)： 2502.
  9. 9. Han JY, Lee GK, Jang DH, et al . Association of p53 codon 72 polymorphism and MDM2 SNP309 with clinical outcome of advanced nonsmall cell lung cancer [Ｊ] . Cancer, 2008; 113(4) ∶799.
  10. 10. Lee JM, Shun CT, Wu MT, et al . The associations of p53 overexpression with p53 codon 72 genetic polymorphism in esophageal cancer [Ｊ] . Mutat Res, 2006; 594(1-2)：181.
  11. 11. Zhu ZZ, Cong WM, Liu SF, et al . Homozygosity for Pro of p53 Arg72Pro as a potential risk factor for hepatocellular carcinoma in Chinese population [Ｊ] . World J Gastroenterol, 2005; 11(2)：289.
  12. 12. Yoon YJ, Chang HY, Ahn SH, et al . MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection [Ｊ] . Carcinogenesis, 2008; 29(6)： 1192.
  13. 13. Santos AM, Sousa H, Pinto D, et al . Linking TP53 codon 72 and P21 nt590 genotypes to the development of cervical and ovarian cancer [Ｊ] . Eur J Cancer, 2006; 42(7)： 958.
  14. 14. Damin AP, Frazzon AP, Damin DC, et al . Evidence for an association of TP53 codon 72 polymorphism with breast cancer risk [Ｊ] . Cancer Detect Prev, 2006; 30(6)：523.
  15. 15. Gochhait S, Bukhari SI, Bairwa N, et al . Implication of BRCA 2-26G ＞A 5′ untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by p53 codon 72 Arg＞Pro polymorphism [Ｊ] . Breast Cancer Res, 2007; 9(5) ∶R71.
  16. 16. Jones JS, Chi X, Gu X, et al . p53 polymorphism and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population [Ｊ] . Clin Cancer Res, 2004; 10(17)：5845.
  17. 17. Crew KD, Neugut AI. Epiclemiology of upper gastrointestinal malignancies [Ｊ] . Semin Oncol, 2004; 31(4)：450.
  18. 18. Forman D, Newell DG, Fullerton F, et al . Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation [Ｊ] . BMJ, 1991; 302（6788）：1302.
  19. 19. Mitsuhashi J, Mitomi H, Tanabe S, et al . Differences in clinicopathological findings, cell kinetics and p53 expression between early gastric cancers with and without Helicobacter pylori infection [Ｊ] . Hepatogastroenterology, 2004; 51(60)：1636.
  20. 20. Wang J, Chi DS, Kalin GB, et al . Helicobacter pylori infection and oncogene expressions in gastric carcinoma and its precursor lesions [Ｊ] . Dig Dis Sci, 2002; 47(1)：107.
  21. 21. 童明宏， 孫晨光. 幽門螺桿菌感染、 p53基因突變與胃癌的相關(guān)性研究 [Ｊ] . 實用腫瘤雜志， 2003; 18(5)：393.