p73基因多态性与食管癌、贲门癌遗传易感性的关系

背景与目的:p73作为一种抑癌基因,其第二外显子非编码区存在两个单核苷酸多态性(G4C14-A4T14),可以形成茎环结构而影响基因表达。本研究旨在探讨河北省食管癌高发区人群中这两个连锁多态性与食管癌、贲门癌易感性的关系。方法:采用病例-对照研究,以聚合酶链反应-限制性片段长度多态性方法,分析348例食管癌患者、259例贲门癌患者和630例健康对照者的p73基因多态性。结果:具有上消化道肿瘤家族史可明显增加食管癌和贲门癌的发病风险,经性别、年龄和吸烟状况校正的OR值分别1.68(95%CI=1.28～2.20)和1.68(95%CI=1.24～2.26)。p73G4C14-A4T14基因型及等位基因型在食管癌患者、贲门癌患者和健康对照中总体分布差异无显著性。在根据吸烟状况和上消化道肿瘤家族史进行分层分析,发现在无上消化道肿瘤家族史亚组中,携带GC/AT基因型明显增加贲门癌的发病风险(OR=1.71,95%CI=1.14～2.57),而其他亚组中未见p73G4C14-A4T14多态性增加食管癌、贲门癌的发病风险。结论:p73G4C14-A4T14多态性中,携带GC/AT基因型明显增加河北省食管癌高发区无上消化道肿瘤家族史人群贲门癌的发病风险。     

p73基因与乳腺癌关系研究进展

p73基因是新近发现的p53基因家族成员之一,其编码的蛋白在结构和功能上与p53基因编码蛋白相似,因此人们认为它是一个候选的抑癌基因。     

p73基因与乳腺癌关系的研究进展

p73基因是新近发现的基因,其结构和功能与抑癌基因p53有高度同源性,并定位于染色体上特殊区域,可能是新的抑癌基因.本文就p73基因特别是其表达两种功能不同而又密切相关的蛋白质即TAp73和DNp73的结构和功能以及p73基因与乳腺癌发生发展中的作用作一综述.     

p21WAF1基因多态性与胃癌易感性关系

目的:探讨p21WAF1基因缺失与多态性及其意义。方法:采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)法和链霉菌抗生物素蛋白-过氧化酶(SP)法分别检测胃癌中p21WAF1基因缺失与多态性和p21蛋白表达。结果:PCR扩增显示,30例胃癌和45例非胃癌标本均无p21WAF1第二外显子缺失。PCR-RFLP发现胃癌和正常胃粘膜p21第二外显子多态性分别为26.7%(8/30)和8.9%(4/45),有显著性差异(P<0.05),且8例具多态性胃癌标本中的正常胃粘膜亦具有这种多态性。p21蛋白阳性表达率,胃癌为43.3%(13/30),非胃癌为100%(45/45),两者有显著性差异(P<0.05),具p21WAF1基因多态性胃癌为37.5%(3/8),与无多态性胃癌45.5%(10/22)无相关性(P>0.05)。结论:胃癌中p21WAF1基因无缺失,而存在多态性。p21WAF1基因多态性和p21表达与胃癌发生有关,但两者无相关性。WAF1     

NAT2基因多态性与膀胱癌遗传易感性的关系

目的　探讨NAT2基因多态性与膀胱癌遗传易感性的关系。方法　以病例对照研究方法 ,采用PCR RFLP技术 ,对 6 9例膀胱癌患者和 88例健康对照者的NAT2基因型进行检测 ,分析NAT2基因型的分布特征。结果　NAT2慢基因型在病例组的频率为 2 6 .1% (18/6 9) ,对照组为 14 .8% (13/88) ,差异有显著性 (P <0 .0 5 ) ,携带慢基因型者患膀胱癌的危险性比携带快基因型者高 2倍。以NAT2快基因型 /不吸烟者为参照 ,慢基因型 /吸烟者患膀胱癌的危险性增加 5 .8倍 (P <0 .0 5 )。在吸烟量 >10PY(1PY =平均每年每天吸烟 2 0支 )的吸烟者中 ,病例组的慢基因型分布频率显著高于对照组 (P <0 .0 5 )。病例组中 ,NAT2基因型与膀胱癌组织分级呈显著相关性 (P <0 .0 5 )。慢基因型在表浅性肿瘤患者中的频率为 12 .8% ,浸润性肿瘤患者则为 5 4 .5 % ,差异有显著性 (P <0 .0 1)。结论NAT2基因多态性与膀胱癌的易感性有关 ,携带慢基因型的人群易患膀胱癌 ,而且肿瘤恶性程度更高。     

NQO1基因多态性与肺癌遗传易感性

目的：探讨依赖还原型辅酶１／２醌氧化还原的酶基因ｃＤＮＡ６００位Ｃ→Ｔ点突变怕致物基因多态必理否与肺癌遗传多态性有关。方法：采用聚合酶锭反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）的分析方法分析队列 肺癌病人与１３６例健康成人对照组ＮＱＯ１的基因多态性。结果：Ｔ等位基因频率在肺癌组和对照组分别为５４％、４３％,两组有显著差异（Ｐ＝０．０２４）。基因型分布在肺癌组和组之间差异显著（Ｐ＝０．００８）     

GSTM1基因多态性与肿瘤遗传易感性研究进展

谷胱甘肽转硫酶(glutathione S-tranferase,GSTs)是一组具有多种生理功能的蛋白质,是与毒物或致癌物的解毒代谢有关的酶类,在机体代谢有毒化合物、保护细胞免受急性毒性化学物质攻击和抑制细胞癌变中起着重要的作用.因此,编码GSTs的GSTM1基因成为近年来研究的热点.最近国内外众多关于GSTM1基因多态性与肿瘤易感性关联的病例对照研究,均提示GSTM1单核苷酸多态性与多个肿瘤的易感性有关.     

p73基因研究进展

ｐ７３基因是Ｋａｇｈａｄ等在１９９７年克隆得到的一个新基因,其编码的蛋白质在序列上与Ｐ５３蛋白有较高的同源性,在功能上与Ｐ５３蛋白有部分重叠,被认为可能是ｐ５３基因家族的一个成员,候选的抑癌基因。１９９８年Ｍｉｎｇ等发现部分癌中ｐ７３高水平表达,且其沉默的等位基因被激活,由此他们认为ｐ７３可能是ｐ５３的一种模拟突变体。     

代谢酶基因多态性与胃癌遗传易感性

肿瘤遗传易感性是目前国内外极其关注的研究领域，不同个体对环境致癌物代谢能力的差异决定了个体对肿瘤的易感性。化学致癌物大多为间接致癌物，需经代谢活化后与细胞生物大分子作用而致癌，经解毒酶作用而失活。毒物代谢过程主要包括两类酶：Ⅰ相酶介导氧化代谢，具有活化作用(包括CYP家族)，Ⅱ相酶具有解毒效应(包括GSTs、     

Breast Cancer Association with CYP1A2 Activity and Gene Polymorphisms - a Preliminary Case-control Study in Tunisia

The aim of the present study was to evaluate the relative contribution of CYP1A2 isoforms (-3860 G/A,-2467T/delT and -163C/A) in control subjects and breast cancer patients to the metabolism of caffeine in humanliver. Restriction fragment length polymorphism analysis of PCR-amplified Fragments (PCR-RFLP) was usedfor the genotyping of CYP1A2 SNPs and HPLC allowed the phenotyping through the measurement of CYP1A2activity using the 17X + 13X + 37X/137X urinary metabolite ratio (CMR) and plasma caffeine half life (T1/2).The CYP1A2 -3860A genotype was associated with a decreased risk of breast cancer. In contrast, distributionsof the CYP1A2 -2467T/delT or -2467delT/delT and -163A/C or A/A genotypes among breast cancer patients andcontrols were similar. When the genotype and phenotype relationship was measured by comparing the meanCMR ratios and caffeine half life within the genotype groups between subjects and breast cancer patients, therewere no significant differences except for -3860 A, most of them being homozygous for the -3860 G/G SNP andhad a significant higher mean CMR ratio and half life than those with -3860 G/A (P=0.02). The results of thispreliminary study show a significant association between CP1A2 -3860 G variant and CYP1A2 phenotype whichmust be confirmed by further large-size case-control studies.     

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。     

Estrogen Receptor Alpha Gene Polymorphisms and Breast Cancer Risk: a Case-control Study with Meta-analysis Combined

Molecular epidemiological studies have shown that gene polymorphisms of estrogen receptor alpha gene(ESR-α) are associated with breast cancer risk. However, previous results from many molecular studies havebeen inconsistent. In this study, we examined two polymorphisms (PvuII and XbaI RFLPs) of the ESR-αgene in 542 breast cancer cases and 1,016 controls from China. Associations between the polymorphisms andbreast cancer risk were calculated with an unconditional logistic regression model. Linkage disequilibrium andhaplotypes were analyzed with the SHEsis software. In addition, we also performed a systematic meta-analysisof 24 published studies evaluating the association. No significant associations were found between the PvuIIpolymorphism and breast cancer risk. However, a significantly decreased risk of breast cancer was observedamong carriers of the XbaI ‘G’ allele (age-adjusted OR = 0.80; 95% CI = 0.66- 0.97) compared with carriers ofthe ‘A’ allele. Haplotype analysis showed significantly decreased cancer risk for carriers of the ‘CG’ haplotype(OR = 0.79; 95% CI = 0.66- 0.96). In the systematic meta-analysis, the XbaI ‘G’ allele was associated with anoverall significantly decreased risk of breast cancer (OR = 0.90, 95% CI = 0.82- 1.00). In addition, the PvuII‘C’ allele showed a 0.96- fold decreased disease risk (95% CI = 0.92- 0.99). In subgroup analysis, an associationbetween the PvuII ‘C’ and XbaI ‘G’ alleles and breast cancer risk was significant in Asians (‘C’ vs. ‘T’: OR =0.93, 95% CI = 0.85- 1.00; ‘G’ vs. ‘A’: OR = 0.82, 95% CI = 0.68- 0.98), but not in Euro-Americans. Thus, ourresults provide evidence that ESR-α polymorphisms are associated with susceptibility to breast cancer. Theseassociations may largely depend on population characteristics and geographic location.     

人类白细胞抗原-E基因多态性与乳腺癌遗传易感性的关系

目的 探讨人类白细胞抗原-E（HLA-E） 基因多态性与中国张家口地区汉族女性乳腺癌遗传易感性的关系。方法 采用聚合酶链反应-序列特异性引物（PCR-SSP）法对中国张家口地区200例乳腺癌患者和114例健康对照人群HLA-E等位基因进行检测。结果 乳腺癌患者和健康对照组均检出两种等位基因：HLA-E*0101和HLA-E*0103;共检出三种基因型：HLA-E*0101/ HLA-E*0101、HLA-E*0101/HLA-E*0103和HLA-E*0103/ HLA-E*0103。其中HLA-E*0103等位基因和HLA-E*0103/HLA-E*0103基因型在乳腺癌患者组的分布频率明显高于健康对照组,差异有统计学意义（P ＜0.01）。且携带HLA-E*0103/ HLA-E*0103基因型的个体乳腺癌发病风险明显增加（OR=2.05,P=0.004）。结论 HLA-E基因多态性与中国张家口地区汉族女性乳腺癌遗传易感性相关,并且HLA-E*0103/ HLA-E*0103等位基因可能是易感基因。     

The Role of Genetic Polymorphisms in Nrf2 and P73 in Egyptian Women with Breast Cancer

Background: Breast cancer is the commonest cancer in Egyptian females. Nrf2 is involved in oxidative stress while P73 functions in response to DNA damage. This study aimed to assess the role of Nrf2 promoter and P73 G4C14 to A4T14 SNPs in breast cancer in Egypt. Patients: Eighty-five female patients with breast tumours (41 malignant, 44 benign) were included. Nrf2 (rs6721961) and p73 (G4A) SNPs were determined by PCR- CTPP assay. Results: Genotype frequencies of the Nrf2 promoter SNP were 34.2% and 37.9% for AA in benign and malignant groups respectively, and 43.9% and 40.5% for CC and, 21.9 % and 21.6% for CA. Genotype frequencies for the P73 G4A SNP were 52.9% and 44.7% for GA in benign and malignant groups respectively, and 47.1% and 55.3% for GG. Discussion: Nrf2 genotypes in pre - and post-menopausal patients, showed significantly different distributions in the 2 patient groups, the AA genotype being significantly more common in pre-menopausal patients. The P73 G4A SNP showed no relation to age of disease onset. Conclusion: The Nrf2 (rs6721961) AA genotype might be related to early breast cancer onset. In contrast the P73 G4A polymorphism showed no relation to either disease risk or age at presentation.     

女性乳腺癌危险因素的病例对照研究

[目的]探讨江苏女性乳腺癌的危险因素。[方法]用病例对照研究的方法,对经病理确诊的206例乳腺癌患者及经年龄频数匹配（±2．5岁）214例对照资料进行非条件Logistic回归分析。[结果]被动吸烟（OR=2．21,95％CI：1．32～3．701、自然流产史（OR=1．71,95％CI：0．65—4．55）、口服避孕药服用史（OR=3．70,95％CI：2．00～6．82）、有良性乳腺疾病史（OR=2．69,95％CI：1．66～4．36）、肥猪肉（OR=2．39,95％CI：1．34～4．28）及腌制类食品年摄入量高（OR=4．71,95％CI：2．91～7．60）、轻体力活动职业（OR=6．29,95％CI：2．95～13．42）可能是女性乳腺癌发生的危险因素。而经常参加体育锻炼（OR=0．44,95％CI：0．26～0．74）、月经初潮年龄晚（OR=0．19,95％CI：0．06—0．65）、鲜奶（0R=0．32,95％CI：0．20～0．511、新鲜豆类（0R=0．07,95％CI：0．04—0．13）和水果年摄入量高（OR=0．30,95％CI：0．18—0．48）则降低乳腺癌发生的风险。[结论]减少口服避孕药、肥猪肉及腌制类食品的摄入,增加新鲜水果、新鲜豆类摄入,加强体育锻炼,对患有良性乳腺疾病的妇女加强体检。加大乳腺癌预防及健康宣教工作可预防乳腺癌的发生。     

CLOCK基因单核苷酸多态性与乳腺癌易感性的病例对照研究

目的：探讨生物钟CLOCK基因的单核苷酸多态性与乳腺癌易感性的关系。方法：采用应用聚合酶链式反应-限制性片断长度多态性（PCR-RFLP）技术检测1 499例中国汉族女性乳腺癌患者和1 592例正常女性对照者CLOCK基因rs3805151位点的基因型,采用SPSS 16.0软件进行数据处理。结果：CLOCK基因CC型、CT型和TT型在病例组和对照组间的分布差异有统计学意义（χ2=9.712,P=0.008）,与CC型相比,杂合型CT可以显著增加乳腺癌的发病风险 （OR=1.41,95% CI：1.07～1.87）,携带T等位基因（CT/TT）的个体乳腺癌风险增加35%（OR=1.35,95% CI：1.04～1.76）。分层分析显示,携带T等位基因绝经后、无肿瘤家族史者、无乳腺良性病史的个体患乳腺癌风险增加。结论：CLOCK基因rs3805151 C>T可增加乳腺癌发病风险,这一结论有待于进一步通过不同种族人群的关联研究以及功能学研究的证实。     

Association of PON1, LEP and LEPR Polymorphisms with Susceptibility to Breast Cancer: A Meta-Analysis

Objective: Breast cancer is the most common cancer in American women, except for skin cancers. In this meta-analysis, the associations of polymorphisms within paraoxonase 1 (PON1), leptin (LEP) and leptin receptor (LEPR) genes with susceptibility to breast cancer were comprehensively evaluated. Methods: A universal search in PubMed, Scopus, CNKI, SID, Web of Knowledge and Google Scholar was performed to identify relevant studies up to 01 May, 2021. The strength of the associations was estimated by Odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: A total of 39 case-control studies including 7 studies with 2005 cases and 2748 controls were on PON1 rs662, 6 studies with 2,031 cases and 1,973 controls on PON1 rs854560, 12 studies with 3,444 cases and 3,583 controls on LEP rs7799039, and 14 studies with 5,330 cases and 6,188 controls on LEPR rs1137101 were selected. Pooled data showed that PON1 rs662 and rs854560 polymorphisms were associated with risk of breast cancer in overall population, but not LEP rs7799039 and LEPR rs1137101. Conclusions: Our pooled data revealed that the PON1 rs662 and rs854560 polymorphisms were significantly associated with an increased risk of breast cancer in the overall population. However, LEP rs7799039 and LEPR rs1137101 polymorphisms were not associated.     

Adherence to the MIND Diet and Risk of Breast Cancer: A Case-control Study

IntroductionNo data are available on the association between adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and breast cancer.Materials and MethodsThis population-based case-control study was conducted among women aged ≥ 30 years, who were residing in Isfahan, Iran. The study included 350 patients with newly diagnosed stage I to IV breast cancer, for whom in situ or invasive status of breast cancer was confirmed by physical examination, mammography, and pathologic verification. Controls were 700 age-matched apparently healthy individuals who were randomly selected from the general population. Dietary data were collected using a validated 106-item Willett-format, semi-quantitative dish-based food frequency questionnaire.ResultsAfter adjustment for age and energy intake, women in the top tertile of the MIND diet score had 60% lower odds of breast cancer than women in the bottom tertile (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.29-0.55). In the fully adjusted model including body mass index, those with the greatest MIND diet scores had 50% lower chance of breast cancer (OR, 0.50; 95% CI, 0.34-0.72) than those with the lowest adherence to the MIND diet. Postmenopausal women with the greatest adherence to the MIND diet were less likely to have breast cancer than those in the bottom tertile (OR, 0.45; 95% CI, 0.30-0.66). In addition, we found a significant inverse association between adherence to the MIND diet and odds of breast cancer among normal-weight women (OR, 0.39; 95% CI, 0.25-0.60).ConclusionAdherence to the MIND diet was associated with a reduced chance of breast cancer in this case-control study.     

CYP1A1 Genetic Polymorphisms and Risk for Esophageal Cancer: a Case-control Study in Central China

The purpose of this study was to evaluate the associations of CYP1A1 genetic polymorphisms with the riskof developing esophageal cancer (EC). A case-control study was carried out in a Chinese population in which157 hospital based EC cases and 157 population based healthy controls with 1:1 match by age and sex wereincluded. PCR based restriction fragment length polymorphisms (PCR-RFLP) were used to detect genotypes incase and control groups. For the CYP1A1 Ile/Val polymorphism, comparing with wild genotype Ile/Ile, both theheterozygote genotype Ile/Val and the combined variant genotype Ile/Val+Val/Val increased the risk of esophagealcancer (OR: 2.05, 95%CI: 1.19-3.54, OR: 1.86, 95%CI: 1.11-3.12). No significant association was found betweenthe CYP1A1 MspI polymorphism and EC. According to analysis of combined genotypes, the TC/AG combinedgenotype which contained both variant alleles of these two polymorphisms increased the risk of developing EC(OR: 2.12, 95%CI: 1.16-3.85). Our results suggested that genetic polymorphisms of CYP1A1 may increase thesusceptibility to EC.