前列腺癌发病率和影响因素

前列腺癌发病率在不同种族和地区有着巨大差异，主要原因包括环境因素和遗传因素的差异。研究表明，不同种族之间遗传基因序列存在差异，可能是疾病易感性不同的遗传基础。文章重点讨论在雄激素合成和代谢过程中相关基因的多态性与前列腺癌发生的相关性。     

基因单核苷酸多态性与宫颈癌易感性研究进展

高危型人乳头瘤病毒的持续感染是宫颈癌发生过程中的必要环境因素,并已得到公认.而HPV感染的最终结局受宿主遗传易感性影响.肿瘤遗传易感性由个体基因组上单个核苷酸变异形成的单核苷酸多态性(SNP)而决定.SNP是人类可遗传的变异中最常见的一种基因,在人类基因组中广泛存在,分布广,适于快速、规模化筛查.本文就基因单核苷酸多态性与宫颈癌易感性的研究进展做一综述.     

p21 Ser31Arg多态性与新疆维吾尔族宫颈癌发生的相关性探讨

目的：探讨p21^WAF1/CIP1基因第31位密码子多态性（p21 Ser31Arg）与新疆维吾尔族（维族）宫颈癌遗传易感性的关系.方法：采用限制性酶切片段长度多态性分析（PCR—RFLP）技术检测100例维族宫颈癌及100例维族正常宫颈组织中D21 Ser31Arg的分布，分析两者之间的相关性结果：1）宫颈癌组中p21 Ser31Arg三种基因型检出率分别为Arg／Arg 13．0％、Ser／Ser 38．0％、Arg／Ser 49．0％、对照组中三种基因型检出率分别为Arg／Arg10．0％、Ser／Ser 39．0％、Arg／Ser 51．0％，两组基因型构成比经统计学分析差异无显著性（x^2=0．444，P〉0．05）。2）p21 Ser31Arg多态性在中分化和低分化鳞癌组之间的构成比差异有显著性（x^2=6．560，P=0．038）。3）p21 Ser31Arg多态性与年龄分组无相关性（X^2=0．341，P〉0．05）。结论：p21 Ser31Arg多态性可能与维族宫颈癌的遗传易感性无明显相关性，但多因素分层分析显示不同的基因型可能与宫颈癌不同的组织分化程度有关．但与年龄分组无关.     

基因多态性与宫颈癌易感性研究进展

目的：总结基因多态性与宫颈癌易感性的研究现状。方法：应用PubMed及CHKD期刊全文数据库检索系统,以“基因多态性、宫颈癌、易感性”等为关键词。检索1999-2013的相关文献80篇,纳入标准：1）宫颈癌易感性研究进展;2）基因多态性与宫颈癌癌易感性的关系。根据纳入标准,最后纳入分析29篇文献。结果：1）DRB1＊15等位基因/DRB1＊15-DQB1＊06单体型与HPV感染或宫颈癌前病变有关,巴西妇女中HLA-DQB1＊05与HPV16阳性宫颈鳞癌呈正相关;2）中国人群中,Pro/Pro基因型在宫颈癌和对照人群中表达有明显差异,葡萄牙北部人群中ASCUS、LSIL、HSIL、ICC患者及正常人宫颈细胞进行检测,未发现p53Arg72Pro在不同人群中的分布有差异;3）TNF-α基因启动子区-238A等位基因可明显降低宫颈癌风险,TNF-α-308G/A多态性与浸润型宫颈癌的发展相关;4）中国妇女人群中,XRCC1 399Gln/Gln基因型与宫颈癌相关性是XRCC1 399Arg/Gln基因型的2.32倍;然而在阿根廷妇女中,XRCC1399Arg/Gln基因型会降低患宫颈癌的风险。结论：1）HLA多态性与宫颈癌易感性和HPV感染相关;2）P53基因多态性与不同地域宫颈癌易感性不同;3）TNF不同位点基因多态性与宫颈癌易感性相关性不同;4）DNA修复基因多态性与宫颈癌易感性关系报道不同。     

GSTM1基因多态性与宫颈癌遗传易感性的关系

目的探讨GSTMI基因多态性与宫颈癌遗传易感性的关系。方法采用多重PCR技术分析130例经病理确诊的宫颈癌病人（病例组）和130例同一地区的健康汉族妇女（对照组）的GSTMI基因型。结果宫颈癌病例组的GSTM1基因纯合缺失率（59．2％）高于对照组（43．9％）差别有显著的统计学意义（x^2=4．986，P=0．026）；GSTM1基因型在各年龄组间分布无差异。结论GSTM1基因纯合缺失能增加宫颈癌发生的危险性，GSTM1基因多态性与宫颈癌遗传易感性密切相关，GSTM1基因纯合缺失是先天遗传而非突变造成的。     

p53基因第72位密码子多态性与HPV相关宫颈癌

流行病学研究显示，感染人乳头状瘤病毒(HPV)后，细胞内P53蛋白失活在宫颈癌发生中起关键作用。近年来国外关于p53基因第72位密码子的多态性与HPV相关宫颈癌发生的遗传易感性研究众多，但结果不尽一致。现主要综述该位点多态性在宫颈癌发生机制中的研究进展。     

基因多态性与胃肠道肿瘤遗传易感性研究进展

近年来基因多态性与疾病遗传易感性的关系，特别是一些功能基因多态与肿瘤的关系日益受到人们的关注。现结合近年来基因多态性与胃肠肿瘤研究的有关文献，介绍代谢酶基因、癌基因、抑癌基因、错配修复基因、细胞周期蛋白基因、免疫相关基因等基因的多态性与胃肠肿瘤遗传易感性的研究进展情况。     

肝癌相关单核苷酸多态性的研究进展

单核苷酸多态性(single nucleotide polymorphism,SNP)作为第3代遗传标记,有助于解释不同群体和个体对肿瘤的易感性以及对治疗预后的敏感性差异.除了环境等外在综合致癌因素外,肝癌的发生和发展很大程度上与个体间基因型的遗传多态性密切相关.全文综述了SNP与肝癌易感性、治疗及预后之间的关系.     

DNA修复基因多态性与肺癌易感性的研究进展

肺癌的发生与个体遗传易感性有关, 其中DNA修复基因多态性可以引起不同DNA损伤反应, 而机体间DNA损伤修复能力的不同与肺癌的发生有密切联系。DNA修复基因多态性与肺癌易感性的关系已成为当前的研究热点。本文回顾了DNA修复基因的作用机制及其多态性与肺癌易感性的国内外研究现状, 就DNA损伤和修复类型、DNA不同修复途径相关基因的作用机制及其多态性与肺癌易感性的关系、DNA修复基因多态性与肺癌化疗敏感性的关系几个方面进行综述。      

细胞毒性T淋巴细胞相关抗原4编码区49位点的基因多态性与宫颈癌遗传易感性的关系

目的 探讨细胞毒性T淋巴细胞相关抗原4(CTLA-4)编码区49位点的基因多态性与宫颈癌遗传易感性的关系。方法 收集314例宫颈癌患者和320例正常对照者的外周静脉血标本,应用聚合酶链反应-限制性片段长度多态性法,检测CTLA-4 +49 A/G多态位点的基因型。采用多因素Logistic回归法,分析基因多态性与官颈癌发病风险的相关性以及与宫颈癌临床病理特征的关系。结果病例组中CTLA-4 +49 A等位基因和AA基因型的频率分别为32.5％和9.6％,对照组中分别为25.8％和5.6％。携带CTLA-4 +49 AA基因型者患宫颈癌的风险是GG基因型的2.06倍(95％ CI 为1.10～ 3.85,P＝0.024)。CTLA-4 +49基因多态与官颈癌临床分期、病理类型、分化程度、肿瘤大小和血清鳞状上皮细胞癌抗原水平等临床病理因素均无关（均P ＞0.05）。结论CTLA-4基因有可能是宫颈癌的遗传易感基因。     

The association between polymorphism of P53 Codon72 Arg/Pro and hepatocellular carcinoma susceptibility: evidence from a meta-analysis of 15 studies with 3,704 cases

Emerging evidence has shown that p53gene participates in human carcinogenesis as tumor suppressors. Polymorphism of p53 gene codon72 arginine (Arg)/proline (Pro) (rs1042522) may influence the function of p53 protein and then affect the processing of carcinogenesis. It has been suggested that p53 codon72 Arg/Pro polymorphism is associated with susceptibility to hepatocellular carcinoma (HCC). However, published results are inconsistent and inconclusive. To examine the validity of the association between the polymorphism and HCC risk, we performed this meta-analysis. We have conducted a search of case–control studies on the associations of p53 codon72 polymorphism with susceptibility to HCC in PubMed, ScienceDirect, BioMed central, Springer, EBSCO, Wanfang databases, and Chinese National Knowledge Infrastructure databases. A total of 15 studies were identified with 3,704 cases and 4,559 controls for codon72 Arg/Pro polymorphism. The result did support a significant genetic association between Pro allele and susceptibility to HCC in all the genetic models. Similarly, subgroup analysis showed significant associations between the Arg/Pro polymorphism and susceptibility to HCC when stratifying by race, gender, source of controls, and hepatitis virus infection status. This meta-analysis suggests that p53 codon72 Arg/Pro polymorphism may be associated with the risk of HCC, especially in subgroup analysis of Asian and Caucasian population, hospital-based population, the female, and the individuals infected with hepatitis virus. However, well-designed studies based on different ethnic groups with larger sample size and more detailed data are needed to confirm these conclusions.     

The significance of p53 codon 72 polymorphism for the development of cervical adenocarcinomas.

Infection with the human papillomavirus is an important co-factor in the development of cervical carcinomas. Accordingly, HPV DNA is recognised in most of these tumours. Polymorphism of the p53 gene, codon 72, is also considered a risk factor in the development of cervical carcinoma. However, this finding is contradicted by several observers. In the present investigation, 111 cases of adenocarcinoma of the cervix collected through the Swedish Cancer Registry and 188 controls (females with normal cytology at organised gynaecological screening) were analysed with regard to p53, codon 72, polymorphism using a PCR- and SSCP-based technique. In the controls, 9% showed pro/pro, 44% pro/arg and 47% arg/arg, whereas in the invasive adenocarcinomas, the corresponding figures were 0%, 29% and 71%, respectively. The difference was statistically significant (P = 0.001). HPV DNA was identified in 86 tumours (HPV 18 in 48, HPV 16 in 31 and HPV of unknown type in 7 cases) and 25 tumours were HPV negative. The p53, codon 72, genotypes observed in HPV-positive and HPV-negative cervical adenocarcinomas were not statistically different (P = 0.690). The results indicate that women homozygotic for arg/arg in codon 72 of the p53 gene are at an increased risk for the development of cervical adenocarcinomas. However, this genetic disposition seems to be unrelated to the HPV infection.     

The effect of TP53 codon 72 and RNASEL codon 462 polymorphisms on the development of cervical cancer in Argentine women

Epidemiological evidence suggests that genetic factors, such as variants in cancer suppressor genes, may play an important role in the etiology of cervical carcinoma. TP53 is an outstanding cell cycle regulator, mutated in most human cancers, and RNASEL is thought to be involved in antiviral and apoptotic responses. To determine whether TP53 Arg72Pro and RNASEL Arg462Gln polymorphisms are associated with susceptibility to cervical cancer, a case-control study of 98 cancer patients and 123 healthy controls was conducted. Cervical samples were genotyped for both polymorphisms by pyrosequencing technology. The association between cervical cancer risk and the studied SNPs was evaluated by logistic regression, and potential gene-gene interactions were studied by Multifactor Dimensionality Reduction analysis. In the single-locus analysis, only the heterozygous TP53 Arg72Pro genotype was significantly associated with the risk of developing a cervical carcinoma, while the RNASEL polymorphism showed no association after age adjustment. In addition, the combination of both polymorphisms gives near-null information gain. Consequently, the effect provided by each single nucleotide polymorphism individually is considered higher than the effect resulting from the interaction between these two genes in cervical cancer risk. These results suggest that a heterozygous TP53 Arg72Pro genotype may contribute to cervical cancer susceptibility.     

p53 codon 72 polymorphism and risk of cervical carcinoma in Moroccan women

Human papillomavirus (HPV) has been implicated in cervical carcinoma and the p53 gene is polymorphic at amino acid 72 of the protein that it encodes. The association between p53 polymorphisms and risk for HPV-associated cervical cancer has been examined, but the results have been conflicting. It has been reported that patients with the arginine form have a higher risk of developing cervical cancer than those with the proline form. The purpose of this study was to examine whether p53 Arg at the polymorphic position 72 could represents a risk factor for women with high-risk HPV-associated malignant cervical lesions. In this study, the polymorphism was examined by both allele-specific PCR and RFLP analysis in 113 patients with cervical cancer and in 100 healthy controls. There was no statistical difference in the subtype distribution between the cervix cancer and the control groups. There was no significant association between genotype distribution of the p53 codon 72 polymorphism and HPV infection. Thus, polymorphism of the p53 itself as well as in combination with HPV infection may not be a genetic risk for cervical cancer and therefore much attention should be paid to other risk factors such as sexual behavior and smoking.     

Cutaneous squamous cell carcinoma and p53 codon 72 polymorphism: a need for screening?

The association between human papillomavirus (HPV)-associated cervical cancer and cutaneous squamous cell carcinoma and codon 72 polymorphism in the p53 gene is not unequivocal. Especially, it is not known whether carriers of the arginine form have an increased risk of cancer that necessitates screening. The alternative is that the polymorphism is a tumor marker instead of a risk factor. We set out a case-control study to determine the risk of squamous cell carcinoma of the skin in individuals with the p53 codon 72 arginine genotype in order to establish the possible need for screening. The distribution of the different p53 codon 72 genotypes was examined in 86 subjects with a history of cutaneous squamous cell carcinoma and in 168 controls. Additionally, 121 subjects who had had histologically proven basal cell carcinoma and 108 subjects who had had non-familial malignant melanoma were tested. p53 polymorphism was evaluated by polymerase chain reaction (PCR) using DNA samples from peripheral blood lymphocytes. In a subgroup of patients with squamous cell carcinoma and controls, the presence of epidermodyplasia verruciformis human papillomavirus (EV-HPV) DNA was determined in plucked eyebrow hair. Differences in the distributions of the genotypes among cases and controls were calculated, and univariate and multivariate analyses were performed to assess the risk to develop cutaneous squamous cell carcinoma in the presence of the p53 codon 72 arginine genotype. Frequency distributions of the three different genotypes (homozygous for the arginine allele, heterozygous for the two alleles, and homozygous for the proline allele) were similar among the squamous cell carcinoma group and the control group: 47.1%, 46.0% and 6.9% versus 47.8%, 45.8% and 6.4%, respectively. Statistical analysis showed no significant differences between these groups. In patients with squamous cell carcinoma and controls who harbored EV-HPV DNA in their plucked eyebrow hair, similar results were obtained. The distributions of the p53 codon 72 genotypes in the basal cell carcinoma and malignant melanoma group were also not significantly different from the control group. p53 codon 72 arginine homozygosity does not appear to represent a significant risk factor for cutaneous squamous cell carcinoma and screening seems not to be indicated. Mol. Carcinog. 30:56-61, 2001.     

Linkage of TP53 codon 72 pro/pro genotype as predictive factor for nasopharyngeal carcinoma development.

Genetic predisposition has been suggested as a cofactor for cancer aetiology and a polymorphism in TP53 codon 72 has been associated as a susceptibility factor for several cancers. Nasopharyngeal carcinoma is a rare neoplasia in western civilizations and genetic predisposition might play an important role in its development. We evaluated the linkage of the polymorphic variants (Arg/Pro) on TP53 codon 72 with nasopharyngeal cancer development in a case-control study with 392 individuals from a northern Portuguese population, including 107 patients with nasopharyngeal carcinoma and 285 healthy controls. This study revealed a three-fold risk for carriers of Pro/Pro genotype either against carriers of Arg/Arg (OR=2.62; 95% CI=1.10-6.30; P=0.016) or total Arg carriers (OR=2.67; 95% CI=1.21-5.90; P=0.012). Moreover, step-wise logistic regression analysis identified Pro/Pro genotype (OR=3.1; 95% CI=1.3-7.3; P=0.009), age >49 at diagnosis (OR=2.5; 95% CI=1.6-4.0; P<0.001) and male gender (OR=2.7; 95% CI=1.6-4.4; P<0.001) as predictive factors for the development of nasopharyngeal carcinoma. These results confirm the data from Asiatic populations suggesting that Pro/Pro genotype represents a stable risk factor for nasopharyngeal carcinoma development in Portugal and that TP53 codon 72 polymorphism can contribute as a genetic susceptibility marker, providing additional information to improve the knowledge about nasopharyngeal carcinoma aetiology.     

Étude du codon 72 du gène p53 dans la prédisposition au cancer du col de l’utérus au Sénégal

Beside human papilloma virus infection, several genetic factors have been involved in susceptibility to cervical cancer. The arginine allele at codon 72 in p53 tumor suppressor gene has been reported to be a risk-factor in different ethnic groups. Our aim was to study this polymorphism as a risk-factor in Senegal. We conducted a case-control association study by recruiting 30 patients with cervical cancer clinically followed up in the Curie Institute in Dakar, and 93 healthy female controls without diagnosed cervical cancer. For each individual, DNA was extracted from whole blood. The codon 72 polymorphism was genotyped by PCR-RFLP. We did not find any association between the arginine allele and susceptibility to cervical cancer in our population (P = 0.354). Moreover, any correlation between the arginine allele and histological lesions was observed. Even if we did not find any correlation between the arginine allele and susceptibility to cervical cancer, p53 as a tumor suppressor gene remains a good genetic marker in tumours biology.     

p53 codon 72 polymorphism does not affect the risk of cervical cancer in patients from northern Italy.

A case-control study was performed to investigate the risk of cervical cancer associated with p53 polymorphism at codon 72, encoding either arginine or proline. It has been recently suggested that the arginine isoform increases the susceptibility to invasive cervical cancer; however, data remain controversial. The polymorphism was examined by both allele-specific PCR and RFLP analysis in 101 patients with primary cervical cancer and in 140 healthy women of the same age and from the same geographical area. The distribution of p53 genotypes in cervical cancer patients and in controls was not significantly different (P = 0.445), and homozygosity for arginine at residue 72 was not associated with an increased risk for cervical cancer (odds ratio, 0.81; 95% confidence interval, 0.47-1.42; P = 0.52). Similarly, different genotype distribution and increased risk were not observed when patients versus controls were analyzed according to human papillomavirus status and cancer histotype. Therefore, no evidence of association between homozygosity for p53 arginine and cervical cancer was found in our population sample.     

Linking TP53 codon 72 and P21 nt590 genotypes to the development of cervical and ovarian cancer

TP53 and its downstream effector gene P21 are two important genes in cell cycle regulation. Genetic alterations on p53 and attenuation of p21 expression result in progression through cell cycle G1 checkpoint, which can lead to cancer development. We analysed the frequency of TP53 codon 72 and 3'UTR P21 polymorphisms in 681 blood samples from 371 cervical cancer patients, 122 ovarian cancer patients and 188 healthy controls using AS-PCR and PCR-RFLP. Approximately twofold increased risk of ovarian cancer (OC) was observed for TP53 Pro carriers (P = 0.038), with a significantly higher risk for advanced OC (P = 0.018). Furthermore, among the P21 CC genotypes, TP53 P allele was also associated with a twofold increased risk of OC (P = 0.014) and to a threefold increased risk for advanced OC (P = 0.003) with an attributable proportion of 44.2%. These results were confirmed in an age-adjusted logistic regression analysis. No association was found between these polymorphisms and cervical cancer. Our results suggest that the TP53 codon 72 genotypes may be considered as a molecular marker, contributing to a genetic profile for ovarian cancer in women.     

p53 codon 72 polymorphism (C/G) and the risk of human papillomavirus-associated carcinomas in China

BACKGROUND: Human papillomavirus (HPV) plays an important role in the development of carcinomas at various body sites. It was found previously that the p53 codon 72 polymorphism (C/G) is a high-risk factor for the development HPV-associated cervical carcinoma. However, it still was considered controversial in several studies of cervical and esophageal carcinoma. METHODS: In the current study, the authors used an allele specific polymerase chain reaction (PCR) method to analyze correlation between the p53 codon 72 (C/G) polymorphism and HPV-associated, noncancerous esophageal epithelium as well as esophageal, ovarian, and breast carcinoma in the Chinese population. Esophageal balloon cytology examination samples were obtained from high-incidence and low-incidence populations for esophageal carcinoma in Anyang (Henan Province). RESULTS: Thirty-six of 48 esophageal balloon samples from the high-incidence population were HPV positive, and 13 of 33 esophageal balloon samples from the low-incidence population were HPV positive. Thirty-nine of 62 esophageal carcinoma samples from Anyang Tumor Hospital were HPV positive. Twenty-six of 39 ovarian carcinoma samples from the Second Affiliated Hospital of Inner Mongolia Medical College were HPV positive. Nineteen of 82 breast carcinoma samples from Beijing Cancer Hospital were HPV positive. It is noteworthy that the distribution of the p53 codon 72 Arg homozygous genotype in HPV positive samples of esophageal epithelium, ovarian carcinoma, and breast carcinoma was significantly higher compared with HPV negative tumor samples. (P < 0.05). CONCLUSIONS: The current results suggest that the p53 codon 72 Arg homozygous genotype is one of the high-risk genetic factors for HPV-associated malignancies among the Chinese population.