新疆地区宫颈癌HLA-DQB1等位基因与临床特征及近期疗效相关性研究

目的 分析新疆地区维吾尔族与汉族宫颈癌患者HLA-DQB1等位基因频率差异,探索HLA-DQB1与临床特征和近期疗效之间的关系.方法 纳入2013-05-1-2013-12-30新疆医科大学附属肿瘤医院收治的68例维吾尔族及20例汉族宫颈癌患者,采集外周血并分离提取DNA,检测HLA-DQB1基因.比较不同临床特征和近期疗效之间基因频率的差异.结果 维吾尔族HLA-DQB1* 03基因频率为33.1％,低于汉族的55.0％,差异有统计学意义,P＜0.05;维吾尔族HLA-DQB1*02基因频率为30.9％,高于汉族的10.0％,差异有统计学意义,P＜0.05.维吾尔族HLA-DQB1* 04、HLA-DQB1* 05和HLA-DQB1* 06等位基因频率分别为5.9％、8.8％和21.3％,汉族HLA-DQB1*04、HLA-DQB1*05和HLA-DQB1*06等位基因频率分别为5.0％、12.5％和17.5％,差异均无统计学意义,P＞0.05.HLA-DQB1各等位基因频率在不同年龄分组及HPV16表达分组之间比较,差异均无统计学意义,P＞0.05.治疗有效(CR+PR)患者HLA-DQB1*03基因频率为42.9％,高于治疗无效(SD+ PD)患者的26.0％,差异有统计学意义,P＜0.05.其余各等位基因频率在两组之间比较差异均无统计学意义,P＞0.05.结论 新疆地区维吾尔族宫颈癌患者HLA-DQB1* 03基因频率低于文献报道,HLA-DQB1* 02基因频率高于文献报道;HPV16阳性患者HLA DQB1* 04基因频率高于HPV16阴性患者;治疗有效患者HLA-DQB1* 03等位基因频率高于治疗无效患者;HLA-DQB1* 03等位基因可能与近期疗效有关.     

HLA-DRB1*1501和DQB1*0602与新疆哈萨克族HPV 感染及食管癌发生的相关性研究*

目的:从基因水平探讨新疆哈萨克族食管鳞癌的HPV 16E6 感染及食管鳞癌发生与HLA-DRB1,DQB 1 等位基因的遗传易感性,为寻找哈萨克族食管鳞癌的易感基因提供参考。方法:采用聚合酶链反应（PCR ）技术检测200 例哈萨克族食管鳞癌和150 例哈族萨克正常人群HPV 16E6 基因的表达情况,运用序列特异性引物聚合酶链反应技术（PCR-SSP ）,检测新疆哈萨克族食管鳞癌患者200 例,哈萨克族正常人群食管膜膜150 例的HLA-DRB1*1501和HLA-DQB1*0602的分布。结果:新疆哈萨克族食管鳞癌患者HPV 16E6 感染率为41% ,明显高于哈萨克族正常人群感染率的14%（P<0.001,OR= 3.94）;HPV 16E6 感染与哈萨克族正常人群HLA-DRB1*1501,HLA-DQB1*0602的无相关性（P>0.05）;新疆哈萨克族食管鳞癌患者HLA-DRB1*1501和HLA-DQB1*0602基因分布频率显著高于哈萨克族正常人群（0.455:0.232,P<0.001,OR= 2.78;0.69比0.554,P=0.006,OR= 1.80）;HLA-DQB1*0602基因阳性率在中低分化鳞癌组中（68.8%）的分布高于高分化鳞癌组（31.2%）,差异有统计学意义（P<0.05）。 结论:HPV 16E6 的感染可能是新疆哈萨克族食管癌发生的重要因素之一。HLA-DRB1*1501和HLA-DQB1*0602是哈萨克族食管鳞癌的易感基因,其中HLA-DQB1*0602与哈萨克族食管鳞癌的分化程度有关。      

维吾尔族霍奇金淋巴瘤与HLA-DRB1、DPA1基因多态性的相关性研究

目的：探索人类白细胞抗原（HLA）DRB1和DPA1低分辨等位基因型与维吾尔族霍奇金淋巴瘤（HL）易感性的关系。方法：采用病例-对照研究（1∶2）和DNA直接测序分型（SBT）法,对40例维吾尔族HL患者和80名健康体检者进行HLA-DRB1及DPA1基因分型,分析其与HL发病的相关性。结果：对于HLA-DRB1和DPA1基因,病例组分别检出12和3个低分辨等位基因,对照组中分别检出13和4个低分辨等位基因;HLA-DRB1、DPA1基因座位上等位基因频率分布均满足Hardy-Weninberg遗传平衡检验（P > 0.05）。维吾尔族HL中HLA-DRB1*15、DPA1*03、DPA1*02-DRB1*13基因表达均高于维吾尔族健康对照组（P均<0.05）;而HLA-DRB1*07基因频率低于维吾尔族健康对照组（P < 0.05）。结论：HLA-DRB1、DPA1基因多态性可能与维吾尔族HL的发病存在关联,在揭示HL的发病机制方面有研究价值。     

新疆维吾尔族女性乳腺癌与HLA-DRB1基因多态性的关系及临床意义

目的:研究新疆维吾尔族女性乳腺癌的发生与人类白细胞抗原(HLA) DRB1等位基因多态性的关系,探讨乳腺癌的遗传易感性。方法:分别收集维吾尔族女性乳腺癌患者和健康人外周血标本196和230例,提取细胞基因组DNA,采用序列特异性引物聚合酶链反应(PCR- SSP)和毛细管电泳测序(CE)的方法进行HLA-DRB1基因多态性鉴定。结果：乳腺癌患者外周血DNA的HLA-DRB1*01多态性频率显著高于健康对照(χ²=10.180,OR=4.550,P<0.05),HLA-DRB1*16多态性低于对照(χ²=4.792,OR=0.492,P<0.05),而其他位点多态性两组间的差异无统计学意义(P>0.05)。结论:维吾尔族女性乳腺癌的发生可能与HLA-DRB1等位基因多态性存在密切关系,对于揭示乳腺癌发病机制及临床诊断提供了客观依据。     

中国南方汉族急性淋巴细胞白血病患者572例的HLA基因和单倍型分析

 目的　研究HLA-A、B、DRB1基因和单倍型与中国南方汉族急性淋巴细胞白血病（ALL）的疾病相关性。方法　应用最大似然性方法分别计算南方汉族ALL患者组572例和5645名南方汉族健康供者HLA-A、B、DRB1基因和单倍型频率,采用χ2检验方法比较其分布差异。结果　ALL组HLA-A33、B58和DRB1*17基因频率均低于对照组[HLA-A33（7.15 %比9.3 %,OR＝0.73,P＜0.05）、B58（5.93 %比8.75 %,OR＝0.64,P＜0.05）和DRB1*17（5.15%比6.30 %,OR＝0.82,P＜0.05）];A3、B51和DRB*12基因频率均高于对照组[A3（2.1 %比1.26 %,OR＝1.7,P＜0.05）,B51（7. 25 %比5.78 %,OR＝1.3,P＜0.05）和DRB*12（16.13 %比12.99 %,OR＝1.35,P＜0.05）];HLA-A33-B58-DRB1*17单倍型频率低于对照组（2.46 %比4.14 %,OR＝0.35,P＜0.05）,A2-B51- DRB1*12单倍型频率高于对照组（1.24 %比0.89 %,OR＝1.66,P＜0.05）。结论　携带有A33-B58-DRB1*17单倍型个体可能与降低ALL的发病风险有相关性,A3基因和A2-B51- DRB1*12可能与增加ALL发病风险有弱相关性。     

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。     

NAT1、NAT2基因多态性与广东地区汉族人群喉癌遗传易感性研究

目的:探讨毒物代谢酶NAT1、NAT2基因多态性与广东地区汉族人群喉癌遗传易感性的关系。方法:采用病例-对照研究的方法,检测233例广东地区汉族喉癌和102例健康对照组外周血中NAT1(NAT1*4,NAT1*11,NAT1*10,NAT1*3)、NAT2(WT、M1、M2和M3)基因多态性。结合病历资料分析NAT1、NAT2多态基因与喉癌临床病理特征之间的关系。结果:喉癌患者携带NAT2快基因表型(18.88%)频率小于正常对照组(45.1%)(OR=2.53,P=0.00)。NAT2慢基因表型与重度吸烟在喉癌致病过程中有协同作用(P=0.013,OR=3.42)。NAT2基因表型与喉癌的临床病理特征无关。喉癌与对照组中NAT1多态基因频率无显著性差别。结论:NAT2快基因表型与喉癌的易感性关联,易感性与吸烟发生协同作用。NAT2基因多态性不影响喉癌的发展过程及预后。NAT1基因多态性可能与喉癌的遗传易感性无关。     

HLA-KIR-MICA基因及其NK受体免疫应答与子宫颈癌的相关性

目的探讨广州市汉族人群HLA-KIR-MICA基因及其NK受体免疫应答与子宫颈癌的相关性。方法收集500例子宫颈上皮细胞癌(鳞状细胞癌和腺癌)的初诊患者(宫颈癌组)和100例与宫颈癌组在区域、年龄、种族、婚姻生育史、个人史等方面差异无统计学意义的健康人群(对照组)。采用PCR-SBT法,对所有样本进行HLA等位基因检测、KIR基因和MICA基因检测;采用realtime PCR法进行HPV-E1、HPV-E2、HPV-E4、HPV-E5、HPV-E6、HPV-E7、HPV-L1、HPV-L2的转录水平监控,以及对HPV蛋白表达差异样本进行MICA表达量检测。结果宫颈癌组患者HLA-KIR*1003、HLA-KIR*14、HLA-KIR*17、HLA-KIR*02、HLA-KIR*12等位基因的分布与对照组比较,差异均有统计学意义(P<0.05);宫颈癌组患者MICA*13、MICA*20、MICA*04、MICA*15等位基因的分布与对照组比较,差异均有统计学意义(P<0.05)。结论广州市汉族人群HLA-KIR*02、HLA-KIR*12、HLA-KIR*0801和MICA*04、MICA*15、MICA*17、MICA*0601等位基因可能与宫颈癌的发生相关。     

人乳头状瘤病毒感染及人白细胞抗原-DQB1等位基因多态性与南疆维吾尔族女性宫颈癌的关系

目的 探讨人类乳头状瘤病毒(HPV)感染及人类白细胞抗原(HLA)-DQB1等位基因多态性与南疆维吾尔族女性官颈癌的关系.方法 采用导流杂交基因芯片技术,检测190例南疆维吾尔族女性宫颈癌组织和190例正常维吾尔族女性宫颈组织21种HPV亚型的感染情况.采用聚合酶链反应序列特异性寡核苷酸探针(PCR-SSO)检测其5个HLA-DQB1等位基因的基因频率.结果 (1)在对照组中,HPV感染17例,感染率为8.9%.190例宫颈癌中,HPV感染133例,感染率为70.0%,高于对照组(P<0.05).其中HPV16的感染率最高,为64.7%,也明显高于对照组(3.7%,P<0.05).其他亚型的感染率均远低于HPV16,依次为HPV18(2.6%)、HPV68(2.1%)、HPV45(1.6%)、HPV58(1.6%)、HPV39(1.6%)、HPV31(1.1%)、HPV56(1.1%)及HPV59(0.5%),中国汉族人常见类型HPV53和低危型HPV6的感染率均为0.5%.(2)宫颈癌组和对照组的HLA-DQBI*03基因分布差异有统计学意义(P=0.014),携带HLA-DQB1*03基因者罹患宫颈癌的风险降低31.7%(OR=0.683),其他等位基因与维吾尔族女性宫颈癌的发生无关.(3)携带HLA-DQB1*06基因的宫颈癌患者HPV和HPV16的感染率高于非HLA-DQB1*06携带者(P值分别为0.046和0.025),携带HLA-DQB1*06等位基因的维吾尔族女性更容易被HPV和HPV16感染(OR分别为1.808和1.879).其他等位基因与HPV及HPV16感染无关.结论 南疆维吾尔族女性宫颈癌患者的HPV感染率高于非宫颈癌女性,均以HPV16感染为主.HLA-DQB1*03可能为南疆维吾尔族女性罹患宫颈癌的保护基因.HLA-DQB1*06为HPV和HPV16感染的易感基因.     

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。     

人类白细胞抗原Ⅰ、Ⅱ类等位基因及单倍体多态性与中国南方汉族白血病的相关性

目的探讨人类白细胞抗原(HLA)Ⅰ类(A、B、C)、Ⅱ类(DRB1、DQB1、DPB1)等位基因和单倍体多态性与中国南方汉族急性淋巴细胞白血病(ALL)、急性髓系白血病(AML)以及慢性粒细胞白血病(CML)的相关性。方法收集深圳市血液中心845例中国南方汉族白血病患者(323例ALL、350例AML及172例CML)和745名中国南方汉族健康献血者的外周血样本。应用聚合酶链反应反向序列特异性寡核苷酸探针杂交(PCR-rSSO)及测序分型(PCR-SBT)方法对HLA-A、-B、-C、-DRB1、-DQB1和-DPB1进行基因分型,鉴定HLA等位基因前4位数。采用Arlequin 3.5软件分析HLA单倍体;从HLA低分辨水平(等位基因前2位数)及高分辨水平(等位基因前4位数)分别统计分析HLA等位基因和单倍体多态性与3种白血病的相关性。结果经Bonferroni校正,ALL组A*02(36.22%比28.26%,χ²=13.41,PC<0.01)及其单倍体A*02-B*46-C*01(15.35%比10.23%,χ²=10.90,PC=0.02)、DRB1*12(15.79%比11.10%,χ²=9.02,PC=0.03)、A*02:03(9.75%比5.32%,χ²=14.25,PC=0.002)及其单倍体A*02:03-B*38:02-C*07:02(3.80%比1.51%,χ²=10.41,PC=0.02)的频率均高于对照组,是ALL易感因素;AML组A*11-B*15-C*08-DRB1*15-DQB1*06-DPB1*02的频率高于对照组(1.34%比0.07%,χ²=12.54,PC=0.003),是AML易感单倍体;CML组A*02(36.63%比28.26%,χ²=9.33,PC=0.02)及其单倍体A*02-B*15-C*04(2.17%比0.29%,χ²=11.74,PC=0.02)、DRB1*03:01-DQB1*02:01-DPB1*02:01(1.86%比0.14%,χ²=13.10,PC=0.01)的频率均高于对照组,是CML易感因素;CML组DRB1*13的频率低于对照组(1.45%比5.25%,χ²=9.29,PC=0.03),是CML拮抗基因。结论在HLA低分辨及高分辨水平发现了白血病易感或拮抗HLA等位基因和单倍体,可为探究中国南方汉族白血病发病机制并制订有效治疗策略提供参考。     

Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India

Background: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. Objectives: To study the predispositions of HLA alleles/haplotypes with cervical cancer. Materials and Methods: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. Results: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; < 3.5.10-4), DRB1*14-DQB1*0501 (OR=6.51; <0.039) and A*11-B*07 (OR=3.95; <0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; <0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions 9 and 37 and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. Conclusions: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.     

Major histocompatibility complex class II polymorphisms and risk of cervical cancer and human papillomavirus infection in Brazilian women.

Infection with high-risk human papillomavirus (HPV) is the major risk factor for the development of malignant lesions in the uterine cervix. Environmental, behavioral, and ill-defined genetic factors also have been implicated in the pathogenesis of this disease. Associations between human leukocyte antigens (HLAs) and cervical cancer, precursor lesions, and HPV infections have been reported in several populations. To verify whether HLA-DRB1, -DQA1, and -DQB1 diversity is related to cervical cancer in the Brazilian population, 161 cases and 257 controls were HLA typed. Variants of DQA1 and DQB1 promoter regions were also typed in 92 cases and 228 controls. Polymorphism in HLA genes and promoters was distinguished by PCR-based methods, and the magnitude of associations was determined by logistic regression analysis. DRB1*15 [confounder-adjusted odds ratio (OR), 2.24; 95% confidence interval (CI), 1.29-3.90], DRB1*1503 (OR, 2.52; 95% CI, 1.16-5.48), and haplotype DRB1*15-DQB1*0602 (OR, 2.04; 95% CI, 1.15-3.61) were positively associated with cervical cancer. When we considered only DR15 haplotypes that did not carry the DQB1*0602 allele, the risk attributed to DRB1*15 more than doubled. A negative association was found between DQB1*05 and cervical cancer (OR, 0.57; 95% CI, 0.35-0.92), and similar trends were observed for DQA1*0101/04, DRB1*0101, and DRB1*1302. HPV positivity among controls was associated with DRB1*1503 (OR, 4.60; 95% CI, 1.33-15.9), DRB1*0405 (OR, 6.21; 95% CI, 1.66-23.2), and DQB1*0602 (OR, 2.48; 95% CI, 1.06-5.80). We suggest that HLA class II polymorphisms are involved in genetic susceptibility to cervical cancer and HPV infection in a Brazilian population from an area with a high incidence of this neoplasia.     

骨肉瘤与人白细胞抗原关联的初步研究

目的探索中国汉人骨肉瘤与人白细胞抗原（ｈｕｍａｎｌｅｕｃｏｃｙｔｅａｎｔｉｇｅｎ,ＨＬＡ）相关性。方法应用补体依赖微量淋巴细胞毒技术,检测骨肉瘤组２５例汉族患者及对照组２５０例健康汉人的ＨＬＡ－Ａ、Ｂ、ＤＲ、ＤＱ座位抗原,统计比较患者与对照组各座位抗原频率。结果骨肉瘤组ＨＬＡ－Ｂ３５抗原频率为０．４００,对照组为０．０４８,携此抗原的中国汉人骨肉瘤发病的相对危险率是无此抗原者的１３．２２０倍（Ｐ＜０．０１）。含ＨＬＡ－Ｂ１３抗原的患者预后不良的相对危险率为无此抗原患者的１２．０４８倍（Ｐ＜０．０５）。既携ＨＬＡ－Ｂ１３又含ＨＬＡ－Ｂ３５抗原患者,更表现出预后差的趋势。而含ＨＬＡ－Ｂ４０抗原患者的预后较无此抗原患者,相对安全率为７．０５７倍（Ｐ＜０．０５）。结论ＨＬＡ－Ｂ３５与中国汉人骨肉瘤易感性基因紧密连锁,ＨＬＡ－Ｂ１３和ＨＬＡ－Ｂ４０抗原则可能分别与骨肉瘤恶性基因及抵抗性基因相关联。     

Human leukocyte antigens in 295 Chinese patients with chronic myeloid leukemia

Experimental studies using synthetic peptides identical to the bcr-abl fusion region in chronic myeloid leukemia (CML) patients have revealed that some specific peptides could bind to human leukocyte antigen (HLA) class I and class II molecules. Previous clinical observations have also reported some significant HLA associations with the development of CML in their populations. Due to high diversity of HLA alleles, the present study assessed the possibility of an association of HLA molecules in CML patients living in Jiangsu province, the eastern part of China. HLA-A, B and DRB1 allele distributions in 295 CML patients (aged 4 - 65 years) were analysed and compared with unrelated healthy hematopoietic stem cell donors from the same ethnic and geographic background. By comparison of the HLA gene distribution characteristics between CML and healthy donor populations, differences with statistical significance were found in HLA-A*30 (5.42% versus 9.13%) with odds ratio (OR) 0.57, DRB1*07 (8.14% versus 12.51%; OR = 0.62), and B*81 (0.51% versus 0.09%, OR = 5.44). These results suggest that expression of HLA-A*30, DRB1*07 might imply a protective effect on CML acquisition, while B*81 might be associated with CML susceptive factors in our population.     

Meningioma: is there an association with human leukocyte antigens?

The expression of human leukocyte antigen (HLA) alleles plays an important role in the development and recurrence of benign and malignant diseases. Association of single HLA alleles or haplotypes with neoplastic processes has been investigated previously, and correlation between HLA and solid tumors, such as head and neck cancers or uterine cervical squamous epithelial lesions, were reported. However, there is no published data on the influence of the HLA system on the development of symptomatic cerebral meningioma, a mostly benign intracranial tumor of mesenchymal origin in adults. The present investigation is comparing the frequency of single HLA alleles and haplotypes in 81 adult Caucasian patients with symptomatic central nervous system meningiomas to that of 157 area- and race-matched healthy controls. Both standard serological and molecular genetic (PCR) techniques were used for HLA typing. Our results suggest an association between single HLA alleles and occurrence of clinically symptomatic meningioma. Patients with HLA-A*02 had a 2.5-fold increased risk of meningioma (P = 0.02), and those with HLA-DQB1*05 had a 1.8-fold increased risk of meningioma (P = 0.05). Conversely, HLA-A*01, -B*08, and -DRB1*03 were associated with a 0.4-, 0.5-, and 0.5-fold, respectively, decreased risk of meningioma (P = 0.008, P = 0.05, and P = 0.04). Moreover, the occurrence rate of combinations and estimated haplotypes containing these HLA alleles was strikingly different in meningioma patients compared with controls: significantly increased for the haplotypes HLA-A*02:DRB1*04 (P = 0.02, relative risk = 2.5) and HLA-A*02:DRB1*04:DQB1*0302,DQB1*05 (P = 0.03, RR = 7.5), and significantly decreased for the haplotype HLA-A*01:B*08:DRB1*03 (P = 0.01, relative risk = 0.2). In conclusion, these data suggest that some single HLA alleles and haplotypes may protect from or predispose to developing symptomatic central nervous system meningioma during adult life. These associations may be indicative of the involvement of the immune system in the host antitumor surveillance, recognition, and destruction of de novo arising human tumor cells.     

HLA‐DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma

Increasing evidence suggests that HLA‐DRB1 alleles reduce or increase the risk of developing ulcerative colitis‐associated colorectal carcinoma (CRC) tumors. However, the role of HLA‐DRB1 locus on the susceptibility to develop CRC tumor, in the absence of a history of inflammatory bowel diseases (IBDs), is unclear. The aim of our study was to determine whether HLA‐DRB1 alleles are associated with IBD‐independent CRC tumor. HLA‐DRB1 allele polymorphisms were identified by sequence‐based typing method in 53 CRC patients and 57 sex‐ and age‐matched healthy Caucasian controls. Pearson's chi‐squared analysis with Yate's correction or Fisher's exact test with Bonferroni's correction, as appropriate, were used to compare the allele frequency (AF) differences of HLA‐DRB1 in patients and controls. A total of 29 HLA‐DRB1 alleles were recognized. A detailed study of these alleles allowed to identify DRB1*13:01 and DRB1*11:01 alleles that were significantly associated with an increased and reduced risk to develop CRC tumor, respectively. AF of DRB1*13:01, in CRC patients, was significantly higher than that of healthy controls, even following Bonferroni's correction (p = 0.029). In contrast, the presence of the DRB1*11:01 allele was negatively associated with CRC tumor as evidenced by the significantly lower AF in CRC patients than that of healthy controls (p = 0.005). However, following Bonferroni's correction, the AF of DRB*11:01 lost its statistical significance. These results suggest that HLA‐DRB1*13:01 allele could be a potential marker for predicting genetic susceptibility to CRC tumor. In contrast, the protective role of DRB1*11:01 remains unclear.     

A PRIMARY STUDY OF THE CORRELASTIONS BETWEEN HUMAN LEUKOCYTE ANTIGEN(HLA) AND OSTEOSARCOMA

Ｕｐｔｏｎｏｗｈｕｍａｎｌｅｕｋｏｃｙｔｅａｎｔｉｇｅｎ（ＨＬＡ）ｓｙｓｔｅｍｉｓｔｈｅｍｏｓｔｃｏｍｐｌｅｘｐｏｌｙｍｏｒｐｈｉｓｍｓｙｓｔｅｍｉｎｈｕｍａｎｈｅｒｅｄｉｔｙ．Ｉｔｍｏｄｕｌａｔｅｓｔｈｅｓｕｓｃｅｐｔｉｂｉｌｉｔｙ，ｒｅｓｉｓｔａ...     

Analysis of serum ErbB-2 protein and HLA-DRB1 in Japanese patients with lung cancer

We investigated the relationship between ErbB-2 and HLA in order to clarify the clinical and genetic factors related to Japanese patients with lung cancer. Thirty-nine of the 73 lung cancer patients (53.4%) had elevated levels of ErbB-2. Only seven of 23 (30. 4%) patients with small cell carcinoma had elevated ErbB-2 levels. The prevalence of ErbB-2 positivity was highest (23 of 32; 71.8%) in patients with adenocarcinoma, while that in patients with squamous cell carcinoma was 50% (9 of 18). The frequencies of HLA A33, B44, B62, and B75 were lower in the lung cancer patients than in the control group. HLA-DR9 was higher in frequency in lung cancer patients than in the healthy controls (P<0.05), but HLA-DR6 was lower in frequency in lung cancer patients than in controls (P<0.01). DRB1*0901 was significantly higher in frequency in lung cancer patients than in controls (P<0.05). On the other hand, DRB1*0802, DRB1*1302 and the DRB1*14 group (*1401, *1403, *1405, *1406, and *1407) were completely absent in lung cancer patients. The frequencies of HLA B35, B52, B62, DRB1*0404, and DRB1*0406 were higher in the ErbB-2-positive lung cancer patients than in the ErbB-2-negative lung cancer patients. However, these types of HLA were not included in significant frequencies in our group of lung cancers. Our results suggest that some HLA-antigens/alleles participate in the pathogenesis of lung cancer in Japanese patients. In addition, the relationship between HLA-associated genetic factors and ErbB-2 seems to be weak. These findings suggest that ErbB-2 is correlated with prognostic factors for lung cancer independently of HLA-associated genetic factors.     

Changes in Median Ages at Death from Selected Cancer Types in Relation to HLA-DRB1/DQB1

The median ages at death from cancers between 1985 and 2005 were calculated to demonstrate that inherentanticancer mechanisms may be a common pathway for different cancers. Seventy-eight patients with gastric,liver and lung cancers, were recruited in the solid cancer group. The leukemia group consisted of 31 patientswith three main types of leukemia. The controls were 100 healthy individuals. The samples were typed usingan HLA-DR/DQ PCR-SSP typing kit. The results showed that the median ages at death from all causes were64.7 years in 1985 and 70.1 years in 2005. The range of the median ages at death from all cancers was similarto the corresponding value for deaths attributed to all causes. The frequency of DRB1*03 was 9.6% in the solidcancer group and 3.0% in the control group (p<0.05). The frequency of DRB1*04 in the leukemia group weresignificantly lower than that of the control (p<0.05). DRB1*13 and DQB1*06 frequencies in the leukemia groupwere significantly higher than those of the controls (p<0.05). It is suggested that inherent anti-cancer mechanismsmay be a common pathway for different cancers and are associated with the immune system and HLA.