Study of p53 Gene Codon 72 Arg/Pro Polymorphism in High Incidence Area of Gastric Cancer in Gansu Province_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SHAN Yong ¹ , LI Yumin ² , LI Xun ² , ZHOU Wence ² , SHI Bin ² , HE Mingyan ² , ZHU Kexiang ² , HE Jianhong ² , LIU Tao ³ , HE Wenting ³ , FENG Tielan ⁴

1.School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China;;
2.The Second Department of General Sugery, The First Hospital of Lanzhou University, Lanzhou 730000, China;;
3.Tumor Research Institute, The First Hospital of Lanzhou University, Lanzhou 730000, China;;
4.Operating Room, The First Hospital of Lanzhou University, Lanzhou 730000, ChinaCorresponding Author： LI Yu-min, E-mail: lym19621225@hotmail.com;

Corresponding author：

Keywords：

p53 gene; Single nucleotide polymorphism; Susceptibility; Gastric cancer【Foundation item】 National Natural Science Foundation of China (No.30870964)

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Objective To investigate the relationship of p53 codon 72 polymorphism and susceptibility to gastric cancer in high incidence area of Hexi area of Gansu province. Methods The Arg/Pro polymorphism of p53 gene was detected by real-time PCR in 140 patients with gastric cancer, 110 patients with gastric precancerous lesion and 125 healthy controls; Helicobacter pylori (Hp) infection was detected by Warthin-Starry silver method． Results The Pro allele frequencies of p53 gene in gastric cancer cases (0.543) were higher than those in gastric precancerous lesion (0.482) and controls (0.472). The Pro genotype had a more than 1.846 fold increased risk of gastric cancer 〔OR=1.846; 95% 〗CI (1.006-3.387); P =0.046〕． With statistical analysis， the genotype of p53 gene was correlated with location and Laurens histological type （ P ＜ 0.05）. A significantly higher risk of gastric cancer was also seen in cases with p53 Pro genotype, food, Hp infection, positive mind factor and positive family history． Conclusion There is a b correlation between the p53 gene codon 72 Arg/Pro polymophism and susceptibility to gastric cancer in Hexi area of Gansu province and the Pro/Pro genotype may be one of the major risk factors in patients with gastric cancer.

Citation： SHAN Yong,LI Yumin,LI Xun,ZHOU Wence,SHI Bin,HE Mingyan,ZHU Kexiang,HE Jianhong,LIU Tao,HE Wenting,FENG Tielan. Study of p53 Gene Codon 72 Arg/Pro Polymorphism in High Incidence Area of Gastric Cancer in Gansu Province. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(1): 12-17. doi: Copy

1.	李玉民，石斌，柴琛，等. 甘肃省河西地区胃癌发病状况的调查 [Ｊ] . 中华普通外科杂志， 2004； 19(3)： 183.
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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，孙晨光. 幽门螺杆菌感染、 p53基因突变与胃癌的相关性研究 [Ｊ] . 实用肿瘤杂志， 2003; 18(5)：393.

1. 李玉民，石斌，柴琛，等. 甘肃省河西地区胃癌发病状况的调查 [Ｊ] . 中华普通外科杂志， 2004； 19(3)： 183.
2. 张毅. 抑癌基因失活在多原发性恶性肿瘤发生中的意义 [Ｊ] . 中国普外基础与临床杂志， 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. 赵仲堂主编. 流行病学研究方法与应用 [Ｍ] . 第1版. 北京: 科学出版社， 2000： 523～542.
5. 朱新勇，张同全，王福春，等. p53、 bcl-2和nm23基因在胃癌组织中的表达及其临床意义 [Ｊ] . 中国普外基础与临床杂志， 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，孙晨光. 幽门螺杆菌感染、 p53基因突变与胃癌的相关性研究 [Ｊ] . 实用肿瘤杂志， 2003; 18(5)：393.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study of p53 Gene Codon 72 Arg/Pro Polymorphism in High Incidence Area of Gastric Cancer in Gansu Province

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