p73及p53基因多态性与甘肃武威人群胃癌风险相关性研究

[目的]评价p73基因G4C14-to-A4T14双核苷酸多态性（p73 G4A DNP）和p53基因第72密码子单核苷酸多态性（p53 Arg72Pro SNP）与甘肃武威市人群胃癌高发风险及胃癌不同病理亚型的相关性。[方法]p73G4ADNP的基因分型采用两双相对引物多聚酶链式反应法,p53 Arg72Pro SNP基因分型采用PCR-RFLP法。[结果]共检查胃癌病例385例以及健康对照412人。胃癌组中弥漫型胃癌305例（79.22%）,肠型胃癌80例（20.78%）。对照组p73AT/AT、AT/GC及GC/GC基因型的频率分别为28.15%、47.09%和24.76%;胃癌组分别为21.98%、45.04%和32.98%;以AT/AT作为指示物,胃癌组和弥漫型胃癌的GC/GC纯合子基因型频率均高于对照组,优势比（OR）分别为1.71（95%CI,1.16～2.51）和1.87（1.24～2.81）。对照组p53基因Pro/Pro、Pro/Arg以及Arg/Arg基因型的频率分别为27.18%、50.49%及22.33%;胃癌组则分别为21.82%、45.45%和32.73%;以Pro/Pro为指示物,胃癌组和弥漫型胃癌Arg/Arg基因型频率显著高于对照组,OR分别为1.83（95%CI,1.24～2.70）和2.25（95%CI,1.47～3.43）。[结论]携带p73 G4A GC/GC基因型或p53 Arg/Arg基因型可能会增加胃癌,尤其是弥漫性胃癌的发病风险。     

湖北地区汉族人群p53基因第72位密码子多态性与宫颈鳞癌相关性

[目的]探讨p53基因第72位密码子多态性与湖北地区汉族人群宫颈癌相关性。[方法]采用PCR法检测104例宫颈鳞癌及84例正常宫颈组织标本中p53基因第72位密码子的基因型。[结果]p53基因第12位密码子的3种基因型Arg/Arg、Arg/Pro、Pro/Pro在宫颈鳞癌组比例分别为38.5%、44.2%和17.3%;对照组中分别为52.4%、40.5%和7.1%。Pro/Pro基因型在宫颈鳞癌组中所占比例显著高于正常宫颈组织(P=0.018)。[结论]p53基因第72位密码子Pro/Pro基因型是湖北地区汉族女性发生宫颈鳞癌的遗传易感因素之一。     

p53基因多态性与宫颈癌关系的初步研究

背景与目的:p53基因多态性可影响人乳头状瘤病毒(human papillo-mavirus,HPV)介导的p53降解.本研究的目的是观察p53基因多态性在广东妇女中的分布情况及了解不同p53基因型对宫颈癌发生的影响.方法:收集2002年9月～2003年5月在中山大学肿瘤防治中心妇科治疗的宫颈癌患者46例(病例组)及妇科良性肿瘤患者84例(对照组)的宫颈涂片,用PCR对由涂片中提取的DNA进行HPV DNA检测及p53多态性检测.结果:HPV DNA阳性率在病例组和对照组中分别为47.8%和20.2%.在病例组中,Arg/Arg、Pro/Pro和Arg/Pro基因型分别占56.5%、21.7%和21.7%;在对照组中,Arg/Arg、Pro/Pro和Arg/Pro基因型分别占71.4%、20.2%和8.3%.Arg/Arg(OR,0.520;95%CI,0.245～1.102)和Arg/Pro基因型(OR,1.095;95%CI,0.454～2.639)在病例组和对照组之间无显著性差异;而Pro/Pro基因型在两组之间有显著性差异(OR,3.056;95%CI,1.076～8.678),但在HPV阳性妇女中,这种基因型分布的无显著性差异.结论:Arg/Arg基因型可能不是宫颈癌的高危因素,而Pro/Pro基因型患者可能易患宫颈癌.     

p53 condon72基因多态性与胃癌危险度关系--病例对照研究

目的 :探讨p53密码子 72基因多态性与胃癌危险度的关系 ,及其不同基因型与环境危险因素交互作用对胃癌发病的影响。方法 :在江苏省泰兴市进行以人群为基础的病例对照研究 ,胃癌病例 2 0 4例 ,对照 41 5例。结果 :病例中p53密码子 72的Pro Pro基因型的比例较对照中高 ,Pro Pro或Pro Arg两种基因型与Arg Arg比较OR为 1 50 (1 0 1～ 2 2 3)。p53基因还可与吸烟、饮酒、饮河水、嗜烫食等发生相乘或相加交互作用 ,影响胃癌发病。结论 :p53的Pro等位基因可能与胃癌危险度有关 ,并与其他环境危险因素交互作用 ,增加胃癌发病的危险。     

P53基因CD72Arg／Pro多态性与贲门腺癌生物学行为的研究

目的 探讨P53基因CD72 Arg／Pro多态性与中国汉族人贲门腺癌生物学行为的关系。方法 应用PCR—RFLP法对67例贲门腺癌患者和138名正常对照组人群P53基因CD72Arg／Pro多态性进行检测。结果 病例组P53基因Pro等位基因频率(0．672)和Pro／Pro基因型频率(47．8％)都显著高于正常对照组(0．413和13．0％)(P＜0．01)；携带Pro／Pro基因型者患贲门腺癌的风险比携带Arg／Arg基因型者显著升高，OR为8．30，95％CI：3．49—19．77(P＜0．01)。P53基因型分布和贲门腺癌的病理分化程度存在相关性(P＜0．01)。Pro／Pro基因型频率分布由高到低依次为：低分化组(69．6％)＞中分化组(42．3％)＞高分化组(27．8％)。有淋巴结转移的患者Pro／Pro基因型频率(63.3％)高于无淋巴结转移的患者(35．1％)(P＜0．05)。结论 P53基因Pro／Pro基因型是贲门腺癌的遗传易患因素，携带Pro／Pro基因型的贲门腺癌患者肿瘤恶性程度高、预后较差。     

p53基因第72位密码子突变与食管鳞癌临床病理特征关系的研究

目的研究p53基因第72位密码子（p53 codon72）突变与人食管鳞癌临床病理特征的关系。方法应用聚合酶链反应-限制性片段长度（PCR-RFLP）方法检测118例人食管鳞癌组织及癌旁正常食管黏膜组织的p53 codon72的突变及其差异，并分析其与食管鳞癌临床病理特征的关系。结果p53 codon72的Arg／Arg和Pro／Pro或Arg基因型在癌组织和癌旁正常食管黏膜组织的频率分别为11．0％和38．1％、4．2％和7.60A。p53 codon72Arg／Pro基因型在癌组织和癌旁正常食管黏膜组织分布差异具有显著性（χ^2=55.75，P〈0.01），p53 codon72突变与p53蛋白表达有关（χ^2=15．21，P〈0．01）；且p53 codon72的Pro等位基因与食管癌的TNM分期、分化程度和淋巴结转移均呈显著相关（P〈0．01）。结论抑癌基因p53第72位密码子突变在食管癌发生、发展中可能起重要作用。     

E2钙黏蛋白基因3′2 U TR + 54C/ T 多态与 肺癌的发病风险

 目的　探讨CDH1 基因3′2 U TR + 54C/ T SNP 与中国北方人群肺癌遗传易感性的关系。方法 采用聚合酶链反应2限制性片段长度多态性( PCR2RFL P) 分析方法检测194 名肺癌患者和223 名健康对 照组3′2 U TR + 54C/ T SNP 的基因型。结果　肺癌患者组吸烟个体比例明显高于对照组,吸烟可增加 肺癌的发病风险(OR = 3. 03 ,95 %CI = 2. 03～4. 54) 。肺癌患者组C 等位基因频率(85. 6 %) 显著高于对 照组(76. 9 %) ,两组相比差异有统计学意义(χ2 = 10. 09 , P = 0. 00) ;肺癌患者组与对照组T/ T、T/ C 和 C/ C 基因型频率分别为1. 0 %、26. 8 %、72. 2 %和4. 0 %、38. 1 %、57. 8 % ,与T/ T 或T/ C 基因型相比,携 带C/ C 基因型可显著增加肺癌的发病风险(OR = 1. 89 ,95 %CI = 1. 25～2. 85) 。结论　CDH1 基因3′2 U TR + 54C/ C 基因型可能是中国北方人群肺癌发病的潜在危险因素。     

食管癌中ERCC2/XPD和XRCC1基因多态性的表达

目的:探讨DNA损伤修复基因ERCC2/XPD和XRCC1基因多态性与食管癌遗传易感性的关系。方法:采用病例对照研究设计,选取100例食管癌病例和80例正常对照。选取ERCC2/XPD Lys751Gln和XRCC1 Arg399Gln基因多态性为研究位点,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行多态性检测,应用Logistic回归计算OR值及95%CI,比较不同基因型与食管癌发病风险的关系。结果:病例组和对照组中变异型等位基因ERCC2/XPD Lys751Gln的频率分别是15.7%和13.0%。与野生基因型Lys/Lys相比,携带XPD Lys/Gln和Gln/Gln基因型者患食管癌的危险度比值比(odds ratio,OR)分别是1.94(95%CI:1.22～3.36)和0.56（95%CI:0.15～2.64)。变异型等位基因XRCC1 399Gln的频率在病例组和对照组中分别是29.8%和30.2%,与野生基因型XRCC1 Arg/Arg相比,带Arg/Gln和Gln/Gln基因型者患食管癌的OR分别是0.94(95%CI:0.69～1.31)和1.83(95%CI:0.84～3.89)。分析结果提示饮酒、酸泡菜与XPD Lys751Gln基因多态存在交互作用,交互效应OR值分别为2.24(95%CI:1.18～2.87)和2.53(95%CI:1.71～3.46),携带XPD Lys751Gln和XRCC Arg1399Gln突变基因者若同时暴露于酸泡菜或酒精,则患食管癌的危险显著增加,相较未暴露于上述因素者,OR值均增大。结论:DNA损伤修复基因ERCC2/XPD和XRCC1单核苷酸多态性可能与当地居民食管癌遗传易感性有关,与饮酒、酸泡菜存在交互作用。     

E-钙黏蛋白基因3'-UTR+54C/T多态与肺癌的发病风险

目的 探讨CDHl基因3'-UTR+54C/T SNP与中国北方人群肺癌遗传易感性的关系.方法 采用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)分析方法检测194名肺癌患者和223名健康对照组3'-UTR+54C/T SNP的基因型.结果 肺癌患者组吸烟个体比例明显高于对照组,吸烟可增加肺癌的发病风险(OR=3.03,95%CI=2.03～4.54).肺癌患者组C等位基因频率(85.6%)显著高于对照组(76.9%),两组相比差异有统计学意义(γ2=10.09,P=0.00);肺癌患者组与对照组T/T、T/C和C/C基因型频率分别为1.0%、26.8%、72.2%和4.0%、38.1%、57.8%,与T/T或T/C基因型相比,携带C/C基因型可显著增加肺癌的发病风险(OR=1.89,95%CI:1.25～2.85).结论 CDH1基因3'-UTR+54C/C基因型可能是中国北方人群肺癌发病的潜在危险因素.     

鼠双微体同源基因2遗传多态与结直肠癌患病风险的相关性

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.     

The p53 codon 72 polymorphism and lung cancer risk.

The p53 tumor suppressor gene frequently is mutated in many forms of human carcinomas. A common polymorphism occurs at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). This p53 polymorphism reportedly is associated with lung cancer susceptibility. However, not all investigations have been consistent, and this hypothesized association remains controversial. We tested the hypothesis that the Pro/Pro genotype is associated with increased lung cancer risk in a large case-control study of lung cancer that included 482 cases and 510 controls from the Massachusetts General Hospital in Boston, Massachusetts. DNA from peripheral blood samples was examined by PCR-RFLP. Pro/Pro homozygotes were found more frequently in adenocarcinomas (cases, 16.4%; controls, 12.0%; P = 0.03). The prevalence of the Pro/Pro homozygous genotype increased in frequency with increasing pack-years of smoking. The combined susceptible genotype homozygous Pro/Pro and heterozygous Arg/Pro was associated with a 1.45-fold higher risk of adenocarcinoma compared with Arg/Arg genotype (95% confidence interval = 1.01-2.06; P = 0.04) after adjustment for relevant variables. Lung adenocarcinoma risk increased with the presence of one or both variant alleles across smoking strata. In addition, at each level of smoking (except nonsmoker and light smoker), the risk associated with smoking was higher for the population with the combined variant (Arg/Pro + Pro/Pro) genotype. The risk for the combined genotype was associated with tobacco exposure status. In conclusion, the codon 72 germ-line polymorphism (Arg/Pro) of the common tumor suppressor gene p53 contributes to heritable susceptibility for smoke-induced lung adenocarcinoma. The modifications by p53 polymorphism and pack-years resulted in an increased risk of the susceptible genotype to lung adenocarcinoma. The p53 gene may modulate the response to environment carcinogens and thereby affect the risk of developing lung adenocarcinoma.     

APC mutations are infrequent but present in human lung cancer

Since it is well established that inactivation of p53 is involved in pathogenesis of breast cancer, it seems to be reasonable to assume that p53 genetic polymorphism at codon 72 (p53^Arg72Pro) which affects the function of p53 might have an influence on breast cancer risk. Thus, in the present study, we have studied the association of p53^Arg72Pro polymorphism with breast cancer risk. A case–control study was conducted with 191 breast cancer patients and 218 healthy female controls. p53^Arg72Pro polymorphism was examined in their association with breast cancer risk after adjustment for the epidemiological risk factors. Relationship between p53^Arg72Pro polymorphism and clinicopathological characteristics of breast cancers was also studied. In addition, frequency of somatic p53 mutation was compared according to the genotype of p53^Arg72Pro polymorphism. p53^72Pro/Pro homozygotes showed a significant increase in the risk of estrogen receptor (ER) positive breast cancer (adjusted odds ratio (OR)=2.04, P=0.04) as compared with p53^72Arg/Arg homozygotes, whereas such an association was not found between p53^72Pro/Pro homozygotes and ER negative breast cancer risk. Subset analysis according to menopausal status showed that p53^72Pro/Pro homozygotes were significantly associated with ER positive breast cancer risk in postmenopausal women (adjusted OR=3.42, P=0.01) but not in premenopausal women. Frequency of ER positive tumors was significantly (p<0.01) higher in breast cancer patients with p53^72Pro/Pro genotype (82.8%) than those with p53^72Arg/Arg genotype (54.5%). Mutational analysis of p53 in tumors showed that p53^72Pro/Pro homozygotes had a lower frequency of p53 mutation (3.5%) than p53^72Arg/Arg homozygotes (10.5%). It is suggested that p53^Arg72Pro polymorphism is associated with ER positive breast cancer risk, especially, in postmenopausal women. The higher frequency of p53 somatic mutation in p53^72Arg/Arg homozygotes than p53^72Pro/Pro homozygotes is consistent with the thesis that the function of p53^72Pro/Pro is impaired so that a further alteration of p53 gene is less required in p53^72Pro/Pro homozygotes than p53^72Arg/Arg homozygotes.     

The p53 codon 72 proline allele is associated with p53 gene mutations in non-small cell lung cancer.

The p53 gene plays a critical role in cell cycle control, the initiation of apoptosis, and in DNA repair. An Arg/Pro polymorphism at codon 72 of the p53 gene alters the ability of the p53 protein to induce apoptosis, influences the behavior of mutant p53, decreases DNA repair capacity, and may be linked with an increased risk of lung cancer. To further define the role of the p53 codon 72 polymorphism on DNA repair, lung cancer risk, and mutant p53 function, we examined the effect of this polymorphism on mutation of the p53 gene and patient survival in non-small cell lung cancer (NSCLC). Tumor and nonneoplastic (lung or lymphocyte) samples were collected from 182 patients with NSCLC. p53 mutations were detected by direct sequencing and/or the Gene Chip p53 assay in 93 of 182 (51%) tumors. p53 codon 72 polymorphisms were identified by PCR/RFLP analysis. p53 mutations were significantly (P = 0.01) associated with the number of codon 72 Pro alleles: Pro/Pro homozygotes, 17 of 26 (65%); Arg/Pro heterozygotes, 45 of 79 (57%); and Arg/Arg homozygotes, 31 of 77 (40%). The number of codon 72 Pro alleles was independently associated with p53 mutations (odds ratio, 1.97; 95% confidence interval, 1.14-3.40; P = 0.01) in a multiple logistic regression model. The codon 72 polymorphism did not influence patient survival in either the entire patient group or among patients with p53 mutant tumors. In summary, the p53 Pro allele is associated with an increased frequency of p53 mutations in NSCLC.     

P53 codon 72 polymorphism and risk of gastric cancer in a Chinese population

The p53 gene plays an important role in cell cycle control in response to DNA damage, which may increase the probability of mutations that lead to carcinogenesis. The p53 codon 72 Arg right curved arrow Pro polymorphism has been suggested to be associated with risk for different kind of cancers, but the data on gastric cancer (GC) is very limited. To evaluate the association between this polymorphism and risk of GC, we performed genotype analysis by using a polymerase chain reaction-based restriction fragment length polymorphism assay in a population-based case-control study of 324 GC patients and 317 cancer-free controls in a Chinese population. The controls were frequency-matched to the cases by age, sex and smoking status. The frequency of the p53 Arg allele was 57.4% in the cases and 54.9% in the controls, and the genotype frequencies of p53 Arg/Arg, Arg/Pro, and Pro/Pro were 29.6%, 55.6%, and 14.8%, respectively, in the cases, and 29.6%, 50.5%, and 19.9%, respectively, in the controls (p=0.207). Logistic regression analysis revealed that the p53 Arg allele (Arg/Pro and Arg/Arg genotype) was associated with a borderline significantly increased risk of gastric cancer (adjusted OR=1.44, 95% CI=0.95-2.18), particularly non-cardia gastric cancer (adjusted OR=1.67, 95% CI=1.00-2.77), compared with p53 homozygous Pro allele (Pro/Pro genotype), and the risk was significantly more evident among alcohol drinkers (adjusted OR=2.85, 95% CI=1.37-5.95). While the results suggest that the p53 codon 72 polymorphism may contribute to gastric cancer susceptibility, further larger studies are needed to substantiate our findings and to explore a possible interaction between p53 codon 72 polymorphism and alcohol in the etiology of gastric cancer.     

p53基因codon 72多态性与乳腺癌术后放化疗疗效相关性分析

目的:分析p53基因codon 72多态性与乳腺癌患者术后放化疗的预后相关性。方法:选取北京大学肿瘤医院乳腺癌患者术后接受放化疗427 例,采用聚合酶链反应- 限制性片段长度多态性（PCR-RFLP ）方法分析其p53基因codon 72多态性,比较不同基因型患者间复发及生存的差异。结果:全部患者基因型分布为Pro/Pro 型18.3%（78/427）、Pro/Arg型44.0%（188/427）、Arg/Arg型37.7%（161/427）。3 种基因型间无局部复发生存（LRFS）、无局部区域复发生存（LRRFS ）、无远处转移生存（DDFS）及总生存（OS）均无显著性差异（均P>0.05）。 427 例患者中雌激素受体（ER）阳性为303 例,其中Arg/Arg基因型患者OS明显优于Pro/Pro 基因型患者（χ2=6.330,P=0.042）。 在多因素分析中p53基因codon 72多态性是ER阳性患者LRFS、LRRFS 、DDFS及OS的独立预后因素,Pro/Pro 基因型的患者较Arg/Arg基因型的局部复发风险增加5.9 倍（HR= 5.9,95%CI 1.1～31.1,P=0.036）,局部区域复发风险增加3.1 倍（HR= 3.1,95%CI 1.1～9.1,P=0.039）,远处转移风险增加2.8 倍（HR= 2.8,95%CI 1.3～6.0,P=0.010）,死亡风险增加4 倍（HR= 4.0,95%CI 1.3～12.0,P=0.013）。 结论:在ER阳性的乳腺癌术后接受放化疗患者中,Pro/Pro 基因型的局部及局部区域复发风险、远处转移风险、死亡风险均高于Arg/Arg基因型。      

p53 exon 4 (codon 72) polymorphism and exon 7 (codon 249) mutation in breast cancer patients in southern region (Madurai) of Tamil Nadu

Background: We investigated the association between polymorphisms in the p53 tumor suppressor gene and breast cancer risk in women especially in the Southern part of India. Methods: Genotyping was performed for 50 breast cancer women and 50 controls to determine the status of p53 exon 4 codon 72 polymorphism and exon 7 codon 249 mutation and their possible role in breast cancer risk. Results: Frequency of Arg/Arg at codon 72 was 18% in controls and 28% in patients, Arg/Pro frequency was 56% and 66% , Pro/Pro genotype was 8% in controls and 8% in patients. No significance was observed for breast cancer risk with either Arg/Arg or Pro/Pro genotype in codon 72 polymorphism. Similarly, mutation analysis of exon 7 codon 249 revealed that 72% of breast cancer patients have mutation, which is not statistically significant. However, there is a strong association between increase in exon 7 codon 249 mutation and exposure to pollution. Conclusion: The results suggested that there is no risk for exon 4 with Arg/Arg or Pro/Pro polymorphisms in the p53 gene and there is no strong correlation between breast cancer patients and mutation in exon 7 codon 249 in South Indian women.     

Frequency of TP53 mutations in relation to Arg72Pro genotypes in non small cell lung cancer.

Mutations in the TP53 gene are important events during human lung carcinogenesis. The TP53 gene harbors several polymorphisms, and functional studies have shown that the Arg72Pro polymorphism alters both wild-type and mutant p53 protein activity. Thus, we hypothesized that certain Arg72Pro genotypes may influence the frequency and pattern of somatic mutations in TP53. We therefore examined the status of the Arg72Pro polymorphism and TP53 mutations in 260 non-small-cell lung cancer cases. Here we report a significant trend toward lower frequency of TP53 mutations with increasing number of Pro72 alleles (P = 0.02). Overall, Pro72 allele carriers had significantly lower frequency of TP53 mutations compared with Arg72 homozygotes (P = 0.02). In addition, carriage of the Pro72 variant was related to a lower frequency of mutations affecting the hotspot codon 273. Mutations at codon 273 accounted for 10.6% of the mutations in Arg72 homozygotes and 1.7% of the mutations in Pro72 allele carriers. Our results suggest that the genotype of the Arg72Pro polymorphism may modulate the frequency of TP53 mutations in non-small-cell lung cancer.     

p53 Codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis

p53 codon 72, which produces variant proteins with an arginine (Arg) or proline (Pro), has been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the p53 codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis (H. pylori-CG). We, therefore, examined the polymorphism in 117 gastric cancer patients (72 intestinal type and 45 diffuse type) with H. pylori-CG and 116 H. pylori-CG patients without gastric cancer as controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to analyze the p53 codon 72 polymorphism. The crude genotypic frequencies in the gastric cancer patients were similar to those of the controls. However, when gastric cancers were classified by histologic subtype, the Pro/Pro was more frequent in the patients with diffuse type gastric cancer than in the controls (22.2% of cases vs. 12.1% of controls). The Pro/Pro genotype was associated with a 2.98-fold higher risk of diffuse-type cancer compared to the Arg/Arg genotype (95% confidence interval [CI] 1.07-8.32, p = 0.038). These results suggest that the Pro/Pro genotype at p53 codon 72 contributes to susceptibility for diffuse-type gastric cancer in patients with H. pylori-CG. The p53 codon 72 polymorphism may serve as the genetic marker for the risk assessment of the diffuse-type gastric cancer development in patients with H. pylori-CG.     

P53 Arg72Pro and MDM2 SNP309 Polymorphisms Cooperate to Increase Lung Adenocarcinoma Risk in Chinese Female Non-smokers: A Case Control Study

Background: Cell cycle deregulation is a major component of carcinogenesis. The p53 tumor suppressorgene plays an important role in regulating cell cycle arrest, and mouse double minute 2 (MDM2) is a keyregulator of p53 activity and degradation. Abnormal expression of p53 and MDM2 occurs in various cancersincluding lung cancer. Methods: We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotidepolymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female nonsmokers.Genotypes of 764 patients and 983 healthy controls were determined using the TaqMan SNP genotypingassay. Results: The p53 Pro/Pro genotype (adjusted OR = 1.55, 95% CI = 1.17–2.06) significantly correlated withan increased risk of lung adenocarcinoma, compared with the Arg/Arg genotype. An increased risk was also notedfor MDM2 GG genotype (adjusted OR = 1.68, 95% CI = 1.27–2.21) compared with the TT genotype. Combinedp53 Pro/Pro and MDM2 GG genotypes (adjusted OR = 2.66, 95% CI = 1.54–4.60) had a supermultiplicativeinteraction with respect to lung adenocarcinoma risk. We also found that cooking oil fumes, fuel smoke, andpassive smoking may increase the risk of lung adenocarcinomas in Chinese female non-smokers who carry p53or MDM2 mutant alleles. Conclusions: P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or incombination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers.     

Association Between p53 codon 72 Polymorphism and Cervical Cancer Risk Among Asians: a Huge Review and Meta-analysis

Objective: The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive amore precise estimation of the association between p53 codon 72 polymorphism (Arg72Pro, rs1042522 G>C) andcervical cancer risk among Asians. Methods: A literature search of Pubmed, Embase, Web of Science and CBMdatabases from inception through June 2012 was conducted. The meta-analysis was performed using STATA12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength ofany association. Twenty-eight case-control studies were included with a total of 3,580 cervical cancer cases and3,827 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results showed thatthe Pro/Pro genotype was associated with increased risk of cervical cancer under the heterozygous model (Pro/Pro vs. Arg/Pro: OR = 1.25, 95%CI: 1.02-1.53, P= 0.005). However, no statistically significant associations werefound under four other genetic models (Pro vs. Arg: OR = 0.97, 95%CI: 0.85-1.10, P= 0.624; Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 0.84, 95%CI: 0.70-1.01, P= 0.058; Pro/Pro vs. Arg/Arg + Arg/Pro: OR = 1.13, 95%CI:0.92-1.39, P= 0.242; Pro/Pro vs. Arg/Arg: OR = 0.97, 95%CI: 0.76-1.22, P= 0.765; respectively). In the subgroupanalysis based on country, the Pro/Pro genotype and Pro carrier showed significant associations with increasedrisk of cervical cancer among Indian populations, but not among Chinese, Japanese and Korean populations.Conclusion: Results from the current meta-analysis suggests that p53 codon 72 polymorphism might be associatedwith increased risk of cervical cancer, especially among Indians.