X射线损伤修复交叉互补基因1多态性与非吸烟女性肺癌易感性的关系

目的探讨X射线损伤修复交叉互补基因1（XRCCl）单核苷酸多态性与非吸烟女性肺癌易感性的关系。方法采用以医院患者为基础的病例一对照研究方法,非吸烟女性肺癌患者50例,非癌对照50例。以聚合酶链反应一限制性片段长度多态性（PCR—RFLP）方法检测XRCC1基因Arg399Gln多态性,计算各基因型的比值比（OR）,并探讨烹饪油烟暴露史与多态基因型交互作用对肺癌患癌风险的影响。结果肺癌组与对照组XRCC1 Arg399Gln多态基因型分布差异无统计学意义（P〉0．05）,而腺癌组基因型分布与对照组差异有统计学意义（P〈0．05）。相对于399Arg／Arg基因型,携带至少1个Gin等位基因的个体患肺腺癌的调整OR值为2．19（95％CI为0．73～6．61）,而XRCC1 399Gin／Gin基因型携带者的调整OR值为14．12（95％CI为2、14～92．95）。携带至少1个399Gln等位基因的烹饪油烟暴露者患肺腺癌的风险明显升高,调整OR值为6．29（95％c,为1．99～19、85）。结论XRCC1基因Arg399Gln多态可能是非吸烟女性肺腺癌的遗传易感因素,399Gln等位基因与烹饪油烟交互作用,可提高非吸烟女性肺腺癌的发病风险。     

DNA修复基因ADPRT和XRCC1遗传变异与胃癌发病风险

背景与目的：DNA修复缺陷是肿瘤的遗传易感因素。二磷酸腺苷核糖转移酶（adenosine diphosphate ribosyl transferase,ADPRT）和X线修复交叉互补蛋白1（X-ray repair cross—complementing 1,XRCC1）是碱基切除修复的重要成分。这两个修复蛋白基因均存在功能性遗传。本研究探讨ADPRT 762val→Ala和XRCC1 399Arg→GIn变异单独或联合与胃癌发生风险的关系。方法：以聚合酶链反应．限制性片段长度多态分析方法,检测236例胃癌患者和708例无肿瘤正常对照的基因型。以logistic多因素回归模型计算各基因型的胃癌风险以及基因一基因交互作用对胃癌风险的影响。结果：ADPRT Ala／Ala基因型患胃癌的风险比ADPRT Val／Val基因型高2倍（OR=2．07;95％CI=1．33～3．21;P=0．001）。XRCC1 399Arg—GIn变异单独与胃癌风险无关,但与ADPRT基因型存在基因-基因交互作用,携带ADPRT Ala／Ala和XRCC1 GIn／GIn基因型者患胃癌的风险比携带ADPRT Val／Val和XRCC1 Arg／Arg者高5．32倍（95％CI=1．12～28．57;P〈0．001）。结论：ADPRT 762Val→Ala变异是胃癌的遗传易感因素,而XRCC1 399 Arg→GIn变异有促进ADPRT762 Val→Ala的作用。     

CYP1B1 基因 Leu432Val 位点多态性与头颈癌易感性的 Meta 分析

目的：运用Meta分析方法研究CYPlBl基因Leu432Val位点多态性与头颈癌易感性的发生风险。方法：检索CNKI和PubMed数据库中有关CYPlBl基因Leu432Val位点多态性与头颈癌易感性关联研究的文献。对符合纳入标准的文献进行资料提取后，以OR值和95％可信区间为效应指标，应用STATA11．0软件进行Meta分析，并对发表偏倚进行检测。结果：纳入5个对照研究，共计1580例头颈癌患者和2076例正常对照人群。Meta分析结果显示，总人群中，CYPlBl基因Leu432Val位点多态性与头颈癌易感性之间有显著关联（ValVS．Leu：OR=1．13，95％CI=1．03—1．25，P=0．014；Val／ValV8．Leu／Leu：OR=1．30。95％CI=1．06—1．60，P=0．013；Val／ValVS．Leu／Leu＋Leu／Val：OR=1．23，95％CI：1．05—1．46，P=0．013）。在针对种族的亚组分析中，发现CYPlBl基因Leu432Val位点多态性可能会增加欧洲人群发生头颈癌的风险。结论：CYPlBl基因Leu432Val位点多态性可能是增加欧洲人群发生头颈癌易感性的危险因素。     

碱基切除修复基因多态性与晚期非小细胞肺癌铂类药物化疗敏感性

目的：探讨DNA碱基切除修复通路中XRCC1 Arg399Gln和ADPRT Val762Ala基因多态性与晚期非小细胞肺癌（NSCLC）铂类药物化疗敏感性的关联,并与先前报道的XRCC1 T-77C、Argl94Trp联合分析其预测作用。方法：收集接受铂类药物为基础化疗的晚期NSCLC患者107例,用PCR—RFLP法检测基因型,分析各基因型与铂类药物化疗有效率的关联,并以非条件Logistic回归模型对患者年龄、性别、病理类型、临床分期和治疗方案进行校正。结果：对XRCC1 Arg399Gln多态性进行单因素分析时,发现携带至少1个Gln等位基因的患者的化疗有效率是携带Arg／Arg基因型者的0．42倍（95％CI：0．19—0．93）,差异具有统计学意义;经多因素校正后发现携带至少1个Gln等位基因的患者的化疗有效率是携带Arg／Arg基因型者的0．52倍（95％CI：0．22—1．26）,但差异不再具有统计学意义。对ADPRT Val762Ala多态性进行多因素分析时,发现携带至少1个Ala等位基因的患者的化疗有效率是携带Val／Val基因型者的1．57倍（95％CI：0．67—3．66）。联合分析各患者4个多态性位点的铂类药物敏感基因型的总数目与铂类药物化疗有效率的关联,并经多因素分析校正后,发现携带3—4个铂类药物敏感基因型的患者的化疗有效率是具有0—2个铂类药物敏感基因型者的4．15倍（95％CI：1．54—11．19）,差异具有统计学意义。结论：XRCC1 Arg399Gln多态性与铂类药物化疗敏感性的关系需进一步确认,似乎携带野生型Arg／Arg者对铂类药物化疗更敏感;但未能发现ADPRT Val762Ala多态性与锥苑矧别眇德魄牲存在明显关联;4个多态性位点联合分析的预测效能高于单个位点。     

STK15基因单核苷酸多态与大肠癌风险

目的 探讨STK15 Phe31Ile基因单核苷酸多态与大肠癌风险的关系。方法 以聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析方法,检测了283例大肠癌患者和283例配对的正常对照者STK15Phe 31Ile基因型,比较不同基因型与大肠癌发生和发展的关系。结果 STK15Ile／Ile基因型频率在大肠癌患者和正常对照中的分布差异有统计学意义（50．2％：36．8％;P=0．02）。携带STK15 Ile／Ile基因型者罹患大肠癌的风险比携带STK15 Phe／Phe基因型者增加92．0％（95％CI=1．13～3．27）,此种风险增高在年轻患者中更加显著（OR=2．57;95％CI=1．07～6．17）。未发现STK15 Phe31Ile基因多态与大肠癌转移风险相关。结论 STK15 Phe31Ile多态可能是大肠癌的遗传易感因素。     

XRCC1基因Arg399Gln多态性与中国人群神经胶质瘤易感性Meta分析

目的:探讨XRCC1基因Arg399Gln (G/A)多态性与中国人群神经胶质瘤易感性的关系.方法:计算机检索Pubmed、EMBASE、中国知网、万方期刊、维普等中英文数据库,检索2014年10月之前公开发表的相关文献,对符合标准的文献采用NOS量表评价文献质量,应用RevMan5.1软件进行Meta分析.结果:共纳入9篇与XRCC1基因Arg399Gln多态性与神经胶质瘤易感性相关的病例对照研究,包括7 131例患者,其中病例组3 428例,对照组3 703例,NOS评分≥6分为高质量文献,仅2项研究质量评分＜6.Meta分析结果显示携带A等位基因可增加中国人群神经胶质瘤的患病风险(OR=1.20,95％CI:1.04～1.38,P=0.01).结论:中国人群中XRCC1基因Arg399Gln (G/A)多态性与神经胶质瘤的易感性存在相关性.     

CYP1A1多态性与肺癌遗传易感性的关系

目的探讨代谢酶基因CYP1A1基因多态性与中国汉族人群肺癌遗传易感性之间的相关性。方法应用AS-PCR技术检测150例中国四川汉族肺癌和152例中国四川汉族健康人的CYP1A1基因Exon7多态性分布频率,并分析了Exon7多态性与中国四川汉族人群肺癌遗传易感性之间的相关性。结果CYP1A1Exon73种多态基因型分布频率在两组间比较差异无统计学意义,χ2=0.634,P=0.728。携带突变Val基因型的个体较携带Ile/Ile基因型的个体患肺癌的危险性增加,OR=1.139,95%CI为0.635~2.042,P=0.662。携带突变Val基因型的个体较携带Ile/Ile基因型的个体患肺鳞癌的风险显著增加,OR=3.510,95%CI=1.326~9.293,P=0.011。结论Val突变等位基因可能是中国四川汉族人群的肺癌易感基因。CYP1A1基因Exon7多态性在肺鳞癌发生中起重要作用。     

XRCC 1 Arg399Gln基因多态性对铂类药物化疗胃癌患者预后的影响

目的：研究DNA修复酶X射线损伤交叉互补蛋白1（X-ray repair cross-complementary protein1，XRCCl）基因Arg399Gln多态性对接受铂类药物辅助化疗的胃癌患者预后的影响。方法：选取经病理学确诊的胃癌患者84例，采用含铂类药物的联合化疗方案进行辅助化疗。化疗前采集患者外周血，采用聚合酶链反应．连接酶检测反应（polymerase chain reaction-ligation detection reaction，PCR-LDR）技术检测XRCCl基因Arg399Gln的多态性。结果：84例胃癌患者中，49例（58．3％）携带XRCCl的399Axg／Arg基因型，30例（35．7％）携带Arg／Gln基因型，5例（6．0％）携带Gin／Gin基因型；截止到随访结束，分别有63．1％（53／84）和55．2％（43／84）的患者出现复发和死亡，其中携带Arg／Arg基因型的胃癌患者复发率和死亡率均显著低于携带Arg／Gln或Gln／Gln基因型患者（P〈0.05）。COX多因素分析显示，携带Arg／Arg基因型的患者具有较好的无复发生存期和总生存期预后（P〈0．05）。结论：XRCClArg399Gln基因多态性与术后胃癌患者接受铂类药物化疗后的预后有关，可以在一定程度上判断术后胃癌患者接受铂类药物化疗的预后情况。     

XRCC1多态性与非吸烟女性肺腺癌易感性的关系

背景与目的XRCC1是一种DNA损伤修复基因，其单核苷酸多态性异常是导致DNA修复能力个体差异的重要原因，可能导致个体患肺癌的危险升高。本研究的目的是探讨XRCC1单核苷酸多态性与非吸烟女性肺腺癌易感性的关系。方法采用以医院患者为基础的病例对照研究方法，研究对象包括非吸烟女性肺腺癌患者126例和同期其它肺部疾病对照126例。以聚合酶链反应一限制性片段长度多态性方法分析XRCC1基因Arg399Gln多态性，比较不同基因型与非吸烟女性肺腺癌的关系，并探讨油烟暴露与基因多态交互作用对患癌风险的影响。结果与携带399Arg／Arg基因型者比较，携带399Gln／Gln基因型者患肺腺癌的风险是其8．695倍（95％CI为3．343～22．614）。携带等位基因399Gln又有油烟暴露的个体患肺腺癌的风险明显增高，校正的比值比为5．21（95％CI为1．85～14．70，P〈0．001）。结论XRCC1基因Arg399 Gln多态性可能是非吸烟女性肺腺癌的遗传易感因素。     

XPC基因Ala499Val、Lys939Gln多态与食管癌、贲门癌发病风险的关联

背景与目的：XPC基因参与核苷酸切除修复,该基因存在单核苷酸多态性（SNP）位点,并可能通过SNP位点碱基的改变影响其修复能力及疾病易感性。本研究旨在探讨XPC基因第8外显子Ala499Val及第15外显子Lys939G1nSNP与河北省食管癌、贲门癌高发区-磁县和涉县人群食管鳞状细胞癌（esophageal sguamous cell carcinoma,ESCC）和贲门腺癌（gastric cardiac adenocorcinoma,GCA）遗传易感性的关系。方法：采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）分析方法检测327例ESCC患者、253例GCA患者和612名健康对照的XPC基因第8外显子Ala499Val及第15外显子Lys939Gln SNP的基因型。结果：ESCC患者组、GCA患者组上消化道肿瘤家族史阳性个体比例明显高于对照组,上消化道肘t瘤家族史可增加ESCC、GCA的发病风险（经性别和年龄校正后的OR=1．76和1．77．95％CI=1．34～2．32和1．31～2．39）.ESCC患者组和对照组的XPC基因第8外显子C、T等位基因频率及C／C、C／T、T／T基因型分布差异均无显著性（P〉0．05）。GCA患者组T等位基因频率（26．5％）显著低于对照组（32．5％）,两组相比差异有显著性（x^2=6．12,P=0．01）;与C／C基因型相比,携带C／T基因型可显著降低GCA的发病风险（OR=0．62,95％CI=0．45～0．84）。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与C／C基因型相比,携带C／T基因型可显著降低吸烟个体和家族史阴性个体GCA的发病风险（OR均等于0．57,95％CI=0．36～0．91和0．37～0．88）。在ESCC、GCA患者组和对照组之间,XPC第15外显子A、C等位基因频率及A／A、A／C、C／C基因型分布差异均无显著性（P〉0．05）。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与A／A基因型相比,携带C／C基因型可显著增加非吸烟个体ESCC的发病风险（OR=2．05,95％CI=1．15～3．66）。单体型分析显示,A／T、A／C、C／T、C／C四种单体型,在ESCC患者组与对照组之间分布差异无显著性（P〉0．05）;在GCA患者组与对照组之间分布差异有显著性（P=0．02）。与A／T单体型相比,携带A／C、C／C单体型可显著增加GCA的发病风险（OR=1．35和1．46,95％CI=1．01～1．81和1．06～2．00）。结论：在河北省食管癌、贲门癌高发区一磁县和涉县人群中,携带XPC基因第8外显子C／T基因型可能明显降低GCA的发病风险;第15外显子Lys939Gln SNP可能与ESCC、GCA的发病风险无关,但分层分析发现携带第15外显子C／C基因型可能增加非吸烟个体ESCC的发病风险;携带A／C、C／C单体型可能增加GCA的发病风险。     

Selected genetic polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and risk of head and neck cancer: a pooled analysis.

Tobacco and alcohol consumption are the major risk factors for head and neck cancer, likely due to DNA-damaging processes. Genetic variations in DNA repair genes may affect an individual's susceptibility to head and neck cancer. Pooling data and DNA specimens from three case-control studies in western Washington State, North Carolina, and Puerto Rico, totaling 555 cases (430 whites) and 792 controls (695 whites), we studied the risk of head and neck cancer in relation to common nonsynonymous single-nucleotide polymorphisms in four DNA repair genes: MGMT (Leu84Phe and Ile143Val), XRCC1 (Arg399Gln), XPD (Lys751Gln), and XRCC3 (Thr241Met). All single-nucleotide polymorphisms were assayed in a single laboratory. Among whites, carriage of the MGMT Phe84 [odds ratio (OR), 0.71; 95% confidence interval (95% CI), 0.51-0.98] or Val143 (OR, 0.66; 95% CI, 0.47-0.92) allele was associated with a decreased risk of head and neck cancer; the haplotype distribution for MGMT differed significantly between cases and controls (covariate-adjusted global permutation test, P = 0.012). The XRCC1 GlnGln399 genotype was also associated with decreased risk among whites (OR, 0.56; 95% CI, 0.32-0.94), whereas XPD751 and XRCC3241 were not associated with risk. Alcohol-related risks tended to vary with DNA repair genotypes, especially for MGMT variants, whereas no effect modification was noted with tobacco use. Consistent findings from three case-control studies suggest that selected DNA repair enzymes may play a role in head and neck carcinogenesis.     

The polymorphisms in the MGMT gene and the risk of cancer: a meta-analysis

Polymorphisms in the MGMT gene have been implicated in susceptibility to cancer, but the published studies have reported inconclusive results. The objective of the current study was to investigate the genetic risk of polymorphisms in the MGMT gene for cancer. A meta-analysis was carried out to analyze the association between polymorphisms in the MGMT gene and cancer risk. Five polymorphisms (Leu84Phe, Leu53Leu, Ile143Val, Lys178Arg, and ?485C/A) with 98 case–control studies from 49 articles were analyzed. The results indicated that individuals who carried the Phe/Phe homozygote genotype of Leu84Phe had a 31 % increased risk of cancer compared with the Leu allele (Leu?+?Leu/Phe) carriers (odds ratio [OR]?=?1.32, 95 % confidence interval [CI]?=?1.15–1.52, P?<?0.0001 for Phe/Phe vs. Phe/Leu?+?Leu/Leu). However, there was no significant association between the risk of cancer and the other four polymorphisms (Leu53Leu, Ile143Val, Lys178Arg, and ?485C/A). In further stratified analyses for the Leu84Phe and Ile143Val polymorphisms, the increased risk of cancer remained in subgroups of Caucasians, patients with esophageal cancer for the Leu84Phe polymorphism, and patients with lung cancer for the Ile143Val polymorphism. Results from the current meta-analysis suggested that Leu84Phe and Ile143Val in the MGMT gene are risk factors for cancer. In the future, more studies should be performed to validate our results.     

Polymorphisms in O6-methylguanine DNA methyltransferase and endometrial cancer risk

Cigarette smoking is inversely associated with endometrial cancer risk. Smoking is proposed to decrease risk, in large part, through its anti-estrogenic effects in the uterus. In addition, cigarette smoke is a major source of alkylation damage. The O6-methylguanine DNA methyltransferase (MGMT) gene is responsible for repairing alkylation DNA damage and also has a role in inhibiting estrogen receptor-mediated cell proliferation. Because of MGMT's dual functions, it is a strong candidate gene for endometrial cancer. We assessed the two functional polymorphisms, the Leu84Phe and Ile143Val, in relation to endometrial cancer risk in a nested case-control study within the Nurses' Health Study (cases = 456, controls = 1134). Compared with the 84Leu/Leu genotype, the Phe carriers had a significantly decreased risk of endometrial cancer [odds ratio (OR), 0.72; 95% confidence interval (CI), 0.53-0.96]. We did not observe an association between the Ile143Val polymorphism and endometrial cancer risk overall. We observed a significant multiplicative interaction between the Ile143Val polymorphism and pack-years of smoking on endometrial cancer risk (P, interaction, 0.04); the inverse association of pack-years with endometrial cancer risk was limited to the 143Val carriers (P, trend, 0.01). Compared with women who had the Ile/Ile genotype and never smoked, the 143Val carriers who had >30 pack-years of smoking had a significantly decreased risk of endometrial cancer (OR, 0.41; 95%CI, 0.19-0.86). These data suggest that these two polymorphisms may influence endometrial cancer risk.     

DNA repair single-nucleotide polymorphisms in colorectal cancer and their role as modifiers of the effect of cigarette smoking and alcohol in the Singapore Chinese Health Study.

Recently, we reported that among Singapore Chinese, cigarette smoking and alcohol drinking were independent risk factors for colorectal cancer. Both tobacco smoking and alcohol use are plausible colorectal cancer risk factors, partly due to their ability to induce mutations in the colorectal lumen. In the present study, we investigated the role in colorectal cancer of single-nucleotide polymorphisms in five DNA repair genes: XRCC1 (Arg(194)Trp and Arg(399)Gln), PARP (Val(762)Ala, Lys(940)Arg), XPD (Asp(312)Asn, Lys(751)Gln), OGG1 (Ser(326)Cys), and MGMT (Leu(84)Phe). We conducted this study within the Singapore Chinese Health Study, a population-based cohort of 63,257 middle-aged and older Singapore Chinese men and women enrolled between 1993 and 1998. Our study included 1,176 controls and 310 cases (180 colon and 130 rectum cancer). We observed a positive association between the PARP codon 940 Lys/Arg and Arg/Arg genotypes and colorectal cancer risk [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 1.1-3.1], and an inverse association between the MGMT codon 84 Leu/Phe or Phe/Phe genotypes and colon cancer risk (OR, 0.6; 95% CI, 0.3-0.9), but not rectal cancer (test of heterogeneity by tumor site, P=0.027). We observed evidence that XRCC1 may modify the effects of smoking (interaction P=0.012). The effect of smoking among carriers of the Arg(194)-Gln(399) haplotype was OR=0.7 (95% CI, 0.4-1.1), whereas, among carriers of the Trp(194)-Arg(399) haplotype, it was OR=1.6 (95% CI, 1.1-2.5). We also observed a nonstatistically significant modification of XRCC1 on the effects of alcohol (P=0.245). Whereas alcohol had no effect among carriers of the codon 194 Arg/Arg (OR, 1.0; 95% CI, 0.6-1.7) or Arg/Trp genotypes (OR, 1.1; 95% CI, 0.6-1.9), there was a positive association among carriers of the Trp/Trp genotype (OR, 2.8; 95% CI, 1.0-8.1). Our results support a role for reactive oxygen species as relevant genotoxins that may account for the effects of both smoking and alcohol on colorectal cancer risk.     

Amino acid substitution polymorphisms of the DNA repair gene MGMT and the susceptibility to cervical carcinoma

In the current study, we examined the association between polymorphisms in the O(6)-methylguanine-DNA methyltransferase gene (MGMT) and the risk for cervical carcinoma. We prospectively selected 1012 patients, including 539 with carcinoma and 473 with cervical intra-epithelial neoplasia and 800 healthy women from five hospitals in Zhejiang Province, China. Three single-nucleotide polymorphisms (Leu84Phe, Ile143Val and Lys178Arg) were genotyped, and their association with other epidemiological risk factors was examined. Compared with the MGMT Lys178Lys (AA) or Ile143Ile (AA) genotypes, women homozygous for the Arg178Arg (GG) or Val 143Val (GG) genotypes had a significantly increased risk for cervical carcinoma both in the overall carcinoma group and in the high-risk human papillomavirus-positive group. Compared with using Leu84Leu (CC), Phe84Phe (TT) and Leu84Phe (CT) which did not increase the risk for cervical carcinoma. In addition, using 84Leu (C)-143Ile (A)-178Lys (A) as reference, women carrying 84Phe (T)-143Val (G)-178Arg (G) had a 1.87-fold higher risk for cervical carcinoma (95% confidence interval 1.07-3.27). Similar results were observed for squamous cell carcinomas. The effect of the combination of Arg178Arg (GG) and Lys178Arg (AG) genotypes and the 84Phe (T)-143Val (G)-178Arg (G) haplotype was more pronounced in women infected with high-risk human papillomavirus, an early onset of sexual activity, multiple sexual partners, an early age of the first full-term pregnancy and high parity. These findings suggest that polymorphism in MGMT increases the susceptibility of women to cervical carcinoma, especially in those with high-risk sexual and reproductive histories.     

广西扶绥县肝癌家系XRCC1基因Arg399Gln多态性与肝细胞癌的遗传易感性

目的研究广西扶绥县肝癌家系人群DNA修复基因XRCC1Arg399Gln多态性与肝细胞癌（HCC）遗传易感性的相关性。方法采用病例-对照研究方法,对扶绥县21个肝癌家系人群和10个正常家系人群,运用PCR-RFLP方法分析XRCC1基因Arg399Gln位点多态性,并应用Logistic回归模型分析该位点多态性与肝细胞癌遗传易感性的关系。结果通过XRCC1Arg399Gln基因型检测分型,肝癌家系人群携带变异等位基因Gln的频率为23.68%,正常家系人群为13.16%,等位基因在两组间的分布差异无统计学意义（P〉0.05）。基因型分布符合Hardy-Weinberg平衡定律。正常家系人群中携带Arg/Gln者发生HCC的风险是携带Arg/Arg者的1.622倍（95%CI=0.475～5.541,P=0.440）。肝癌家系人群中除肝癌患者外,携带Arg/Gln、Gln/Gln者发生HCC的风险分别是携带Arg/Arg者的1.198倍（95%CI=0.362～3.968）和2.964倍（95%CI=0.434～20.220,P分别为0.768、0.267）。结论广西扶绥县肝癌家系人群中,XRCC1399Arg/Gln基因型和Gln/Gln基因型者患HCC的风险较Arg/Arg基因型者有增加的趋势,但不存在显著相关性。     

Polymorphisms of STK15 (Aurora-A) gene and lung cancer risk in Caucasians

STK15/Aurora-A is a centrosome-localized serine/threonine kinase that functions primarily in centrosome maturation and mitotic spindle assembly. In a large lung cancer case-control study of 1401 cases and 1397 controls including three ethnic groups, we examined the associations between two non-synonymous SNPs (Phe31Ile and Val57Ile) of the STK15 gene and lung cancer risk. There were statistically significant differences in the distribution of the genotypes (P<0.0001) and haplotypes (P<0.0001) by ethnicity for the Phe31Ile, but not the Val57Ile variant. Caucasians with the homozygous variant Phe31Ile genotype (Ile/Ile) were at a significantly reduced risk for lung cancer [odds ratio (OR)=0.63, 95% confidence interval (CI)=0.41-0.96]. The variant allele of Val57Ile was not associated with lung cancer risk overall. However, men with the homozygous variant genotype (Ile/Ile) had a reduced lung cancer risk as compared with men with the wild-type genotype (Val/Val) (OR=0.42, 95% CI=0.19-0.94). When we performed joint analysis of these two polymorphisms, compared with the reference group (TT+GG, 40.99% of controls), homozygous Ile31 allele/wild-type Val57 allele (AA+GG) carriers (5.45% of controls) exhibited a reduced lung cancer risk (OR=0.78, 95% CI=0.63-0.97). This is the first epidemiological study to report significant associations between STK15 polymorphisms and lung cancer risk.     

Functional STK15 Phe31Ile polymorphism is associated with the occurrence and advanced disease status of esophageal squamous cell carcinoma

STK15/BTAK/Aurora-A involved in regulating centrosomes and chromosome segregation is amplified and overexpressed in human cancers. A T91A polymorphism in STK15 causes Phe31Ile substitution, and the 31Ile variant has been shown to be preferentially amplified and associated with degree of aneuploidy in human tumors. We genotyped 656 patients with esophageal squamous cell carcinoma (ESCC) and 656 controls for the polymorphism to examine the hypothesis that the STK15 variation may affect individual susceptibility to the occurrence and aggression of ESCC. It was found that the Ile/Ile genotype was significantly associated with increased risk of ESCC occurrence [odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.36-2.85] compared with the Phe/Phe genotype. The 31Ile allele frequency significantly increased as ESCC stage increased (trend test, P = 0.006). Patients with the Ile/Ile genotype had an increased risk for invasive disease (stage II-IV; OR = 2.13, 95% CI = 1.04-4.39) or metastatic disease (stage III and IV; OR = 2.31, 95% CI = 1.06-5.05) compared with those with the Phe/Phe genotype. A positive correlation between the Ile/Ile genotype and high ESCC grade was also observed. Our results demonstrate for the first time that the STK15 polymorphism is a genetic susceptibility factor for the occurrence and aggression of ESCC.