CYP1A1、GSTM1基因多态性与肺癌易感性的研究

目的:探讨CYP1A1、GSTM1基因多态性与肺癌易感性之间的相关性。方法:利用RFLP-PCR(限制性片段长度多态性-聚合酶链反应)方法检测65例原发性肺癌和60例非肿瘤患者CYP1A1、GSTM1基因,再用NcoI及HinfI两种内切酶识别CYP1A1等位基因亚型。结果:1)肺癌组与对照组CYP1A1等位基因型Ile/Ile、Ile/Val、Val/Val的频率总体分布无显著性差异;但肺癌组CYP1A1(Val/Val)基因型频率(18.5%)明显高于对照组(8.3%),两组差异有显著性(P<0.05)。2)肺癌组GSTM1(-)基因型的频率(63.1%)明显高于对照组(45.0%),P<0.05。3)两种等位基因联合分析发现,与携带CYP1A1(Ile/Ile)/GSTM1(+)基因型的个体相比:CYP1A1(Ile/Ile)/GSTM1(-)以及CYP1A1(Ile/Val+Val/Val)/GSTM1(+)基因型个体患肺癌的风险度较高,OR分别为3.82(95.0%CI,1.27～11.45)和3.5(95.0%CI,1.18～10.41);而CYP1A1(Val/Val)/GSTM1(-)基因型个体患肺癌的风险度最高,OR为10.5(95.0%CI,1.70～64.73)。4)进一步分层分析发现,CYP1A1(Ile/Val+Val/Val)等位基因型主要增加鳞癌的危险性;而GSTM1基因型组织类型无明显的相关性。5)在分析吸烟对肺癌易感性的影响时发现,CYP1A1(Ile/Val+Val/Val)及GSTM1(-)等位基因型与吸烟有协同作用,并与至发病时的累积吸烟量有关。结论:CYP1A1(Val/Val     

CYP1A1 MspI多态性与子宫内膜癌易感性的病例对照研究

自20世纪60年代以来，上海市区子宫内膜癌发病率逐年上升，且发病年龄有年轻化的趋势。子宫内膜癌的发病机制目前还不十分明确，多数流行病学研究显示子宫内膜癌的危险因素都与雌激素有关，雌激素水平升高导致的内膜增生及DNA损伤被认为是子宫内膜癌发生的主要机制。     

分化相关基因1在Ⅰ型子宫内膜癌中的表达

[目的]检测NDRG1基因在正常子宫内膜和Ⅰ型子宫内膜癌中的表达，探讨其在Ⅰ型子宫内膜癌发生中的作用机制。[方法]应用免疫组化、原位杂交及RT—PCR技术检测NDRG1基因在正常子宫内膜与Ⅰ型子宫内膜癌中的表达。[结果]免疫组化结果显示，NDRG1蛋自在正常子宫内膜和Ⅰ型子宫内膜癌中的表达率分别为12．5％和83．5％，有显著性差异（P=0．000）；原位杂交结果显示．NDRG1 mRNA在10例正常子宫内膜中只有2例表达．而在30例Ⅰ型子宫内膜癌中有22例表达，有显著性差异（P=0.007）；RT-PCR结果显示，NDRG1mRNA在Ⅰ型子宫内膜癌中的表达比正常内膜增高3倍（P=0.000）。[结论]NDRG1在子宫内膜癌中在蛋白水平和mRNA水平与正常子宫内膜相比都明显升高。它可能是一种肿瘤相关基因，其异常表达可能参与了Ⅰ型子宫内膜癌的发病机制。     

Importin 13在子宫内膜异位症和子宫内膜癌中的表达及意义

背景与目的:正常情况下的子宫内膜干/祖细胞有助于子宫内膜的生理性修复,而子宫内膜干/祖细胞的异常增殖和异常分化则会导致子宫内膜疾病(如子宫内膜异位症和子宫内膜癌)。Importin 13(IPO13)是importinβ家族新成员的一个核质双向的转运受体蛋白,是角膜上皮干细胞的一个标记,在维持干细胞的性状、高增殖潜力、低分化状态,调节细胞分化以及小鼠生殖细胞减数分裂上具有重要的作用。本文探讨成体干细胞标记IPO13在子宫内膜异位症和子宫内膜癌中的表达及意义。方法:手术取正常子宫内膜组织40例(对照组),其中增生期和分泌期各20例,异位子宫内膜组织20例(异位症组)和子宫内膜癌病灶组织20例(内膜癌组)。采用免疫组化SP法检测IPO13蛋白在细胞内的定位;采用实时荧光定量PCR技术(real-time quantitativepolymerase chain reaction,RT-PCR)检测IPO13 mRNA的表达;Western blot检测IPO13蛋白的表达。结果:IPO13蛋白在内膜癌、异位症及正常对照组中腺上皮细胞和间质细胞的细胞质和细胞核中均有表达。IPO13蛋白在对照组增生期表达量(0.52±0.30)明显高于分泌期(0.25±0.04,P<0.05);IPO13蛋白在异位症组表达量(0.81±0.12)明显高于对照组增生期及分泌期(P<0.05);IPO13蛋白在内膜癌组表达量(1.21±0.11)明显高于异位症组(P<0.05)。IPO13 mRNA在对照组增生期表达量是分泌期的3倍(P<0.05);IPO13 mRNA在异位症组中表达量是对照组分泌期的6倍(P<0.05),增生期的2.5倍(P<0.05);IPO13 mRNA在内膜癌组表达量是异位症组的2倍(P<0.05)。结论:IPO13在子宫内膜癌中及异位症组中表达明显高于对照组,推测其高表达与子宫内膜癌及子宫内膜异位症发病密切相关。     

CA-125与子宫内膜抗体测定在子宫内膜异位症诊断中的价值

测定28例子宫内膜异位症患者及14例正常健康妇女血清CA－125和子宫内膜抗体（EMAh）水平。结果，血清CA－125浓度与子宫内股异位症临床分期呈正相关，Ⅲ、Ⅳ期子宫内膜异位症患者血清CA－125明显高于对照组；子宫内膜异位症患者血清EMAb明显高于对照组。两者用于子宫内膜异位症诊断的敏感性分别为71．43％和82．14％，特异性分别为57．21％和57．14％。     

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。     

南京市人群NQO1、CYP1A1、mEH基因多态性与肺癌易感性研究

目的：探讨南京市人群人NQO1，CYP1SA1，mEH-exon3,mEH-exon4基因多态性与肺癌易感性的关系。方法：用病例－对照研究方法，收集南京市区原发性肺癌患者84例，其中鳞癌35例，腺癌49例，同时选择对照84例，采用PCR技术，对样本NDA进行NQO1，CYP1A1，mEH-exon3,mEH-exon4基因的检测，并分析各基因型与肺癌易感性的关系。结果：南京市区人群NQO1，CYP1A1和mEH-exon4与肺癌易感性没有明显关系。mEH-exon3基因型与肺鳞癌发生有关，野生型个体可降低肺鳞癌发病的风险（OR＝0．32，95％CI：0．0078－0．63），杂合型和突变型个体患肺鳞癌的危险性明显高于野生型个体（OR＝3．1，95％CI：0．08－6．12），考虑吸烟因素后，mEH-exon3基因型与吸烟者肺癌发生有关，野生型个体可使肺癌发病风险性降低（OR＝0．18，95％CI：0．06－0．29），杂合型和突变型个体患肺癌的危险性增高（OR＝5．66，95％CI：2．01－9．30）。结论：南京市人群中NQO1，CYP1A1，mEH基因的分布情况与国内外的相关报道存在一定差异；种族差异，地域不同可能是造成上述基因分布不同的重要原因，南京市人群中mEH-exon3基因杂合型和变型与肺鳞癌发生有关，与吸烟者肺癌发生关系更为密切。     

CA—125与子宫内膜抗体测定在子宫内膜异位症诊断中的价值

测定２８例子宫内膜异位症患者及１４例正常健康妇女血清ＣＡ－１２５和子宫膜抗体（ＥＭＡｂ）水平。结果，血清ＣＡ－１２５浓度与子宫内膜异位症临床分期呈正相关，Ⅲ、Ⅳ期子宫内膜异位症患者血清ＣＡ－１２５明显高于对照组；子宫内膜异位症患者血清ＥＭＡｂ明显高于对照组。两者用于子宫内膜异位症诊断的敏感性分别为７１．４３％和８２．１４％，特异性分别为５７．２１％和５７．１４％。     

KLF4与S100A14在子宫内膜异位症相关性卵巢癌中的表达及临床意义

目的:探求子宫内膜异位症相关性卵巢癌中Krüppel样因子4（KLF4）与钙离子结合蛋白14（S100A14）的表达情况及临床意义。方法:免疫组化判定KLF4及S100A14分别在36例正常/良性卵巢组织（对照组）、30例卵巢子宫内膜异位症组织（ovarian endometriosis，OE）和49例子宫内膜异位症相关性卵巢癌组织(endometriosis associated ovarian carcinoma，EAOC)中的表达情况，并分析二者与EAOC患者相关临床参数的关系。结果:KLF4在对照组、OE组以及EAOC组中的阳性表达率分别为72.2%（26/36）、63.3%（19/30）、32.7%（16/49），差异有统计学意义（P＜0.01）。S100A14在三组中表达的阳性率分别为61.1%（22/36）、63.3%（19/30）、87.8%（43/49），差异有统计学意义(P＜0.05)。在EAOC中，KLF4表达与淋巴结转移有显著相关性（P＜0.05）。KLF4与S100A14呈负相关(r=-0.138)。结论:KLF4低表达和S100A14高表达可能参与了卵巢子宫内膜异位症恶变，同时KLF4可能促进了EAOC的转移。     

CYP1A1和GSTM1基因多态性与肺癌易感性的Meta分析

目的探讨CYP1A1和GSTM1基因多态性与个体肺癌易感性的关系。方法全面检索相关文献,应用Meta分析方法对各研究进行数据的合并与分析。结果共8篇文献入选,累计肺癌病例1067人,对照1416人,分别对CYP1A1*A和GSTM1-、CYP1A1*B/C和GSTM1+、CYP1A1*B/C和GSTM1-联合基因型进行统计分析。异质性检验χ2值分别为6.43、8.83与9.63,P>0.05,文献有同质性,各合并OR及95%CI分别为1.36(1.09~2.77)、1.65(1.26~2.15)和2.01(1.57~2.59)。结论CYP1A1和GSTM1突变基因型为罹患肺癌的易感基因型,且两者存在协同作用,在肿瘤防治方案中应加以重视从而采取相应措施达到有效预防肿瘤的目的。     

CYPlAl和CYPlA2基因多态性与汉族女性乳腺癌的关系

目的 探讨CYP1A1基因MspⅠ位点与CYP1A2基因C734A位点多态性与汉族女性乳腺癌的关系.方法 应用聚合酶链反应-限制性片段长度多态性技术和限制性核酸内切酶酶切的方法,检测2011年9月至2012年8月在四川省医学科学院四川省人民医院确诊的144例女性乳腺癌患者（乳腺癌组）和152例同期健康体检正常女性（对照组）CYP1A1基因MspⅠ与CYP1A2基因C734A多态性位点的基因型,用χ2检验比较两组等位基因频率的差异.结果 在乳腺癌组与对照组中,CYP1A1基因MspⅠ位点T等位基因频率分别为0.73和0.65,两者差异有统计学意义（χ2=4.94,P=0.03）,C等位基因与T等位基因相比,乳腺癌发病风险OR为0.67 （95%CI：0.47～0.96）;CYP1A2基因C734A位点C等位基因频率分别为0.26和0.29,两者差异无统计学意义 （χ2=0.63,P=0.43）.将乳腺癌组按照ER、PR表达与否进一步分组后,CYP1A1基因MspⅠ与CYP1A 2基因C734A 2个多态性位点的等位基因频率在ER（＋）与ER（-）组之间以及PR（＋）与PR（-）组之间差异均无统计学意义[ER（＋）组比ER（-）组：χ2=0.34、0.01;PR（＋）组比PR（-）组：χ2=0.60、0.68;P均〉0.05].结论 汉族女性CYP1A1基因MspⅠ位点多态性与乳腺癌相关联.     

四川人群中CYP1A1基因Ile-Val和Msp1位点多态性与肺癌易感性的研究

目的　探讨细胞色素P45 0 (CYP1A1)基因异亮氨酸 (Ile) 缬氨酸 (Val)位点和Msp1位点多态性和肺癌易感性的相关关系。方法　以病例对照的研究方法 ,采用PCR RFLP和ASA PCR技术检测 82例原发性肺癌和 91例对照的CYP1A1基因Ile Val位点和Msp1位点多态性。 结果　Ile Val三种多态基因型在肺癌组和对照组分布差异有显著性 (P <0 .0 5 ) ,Ile/Val、Val/Val基因型在肺癌组的分布频率明显高于对照组 ;logistic回归分析结果显示Ile/Val、Val/Val基因型患肺癌的危险分别是Ile/Ile基因型的 1.969倍和3 .15 0倍 ;当按吸烟分层后 (将Ile/Val、Val/Val基因型合并分析 ) ,吸烟组中Ile/Val、Val/Val合并基因型患肺癌的危险是Ile/Ile基因型的 3 .0 5 9倍 ,而在不吸烟组其OR为 1.687;Msp1位点多态性在肺癌组和对照组差异无统计学意义。结论　CYP1A1第 7外显子的Ile/Val、Val/Val基因型与肺癌的易感性有关 ,可望作为肺癌易感人群筛选的重要指标 ;尚不能认为Msp1多态性与肺癌的易感性有关     

CYP17 &; SULT1A1 gene polymorphisms in Indian breast cancer

BACKGROUND: Breast cancer is the most common cancer among women worldwide. Life-time exposure to steroid hormones, especially estrogen, is a major risk factor for breast cancer. Functional polymorphisms in genes encoding steroid metabolizing enzymes may thus be important as biomarkers of individual susceptibility to breast cancer. The CYP17 and SULT1A1 genes encode for two enzymes involved in hormone biosynthesis and metabolism. Single nucleotide polymorphisms of these genes may result in inter-individual variability in steroid hormone biosynthesis and metabolism thus influence the development of breast cancer. METHODS: We tested this hypothesis by conducting a case - control study on a group of 140 breast cancer cases and 140 healthy age-matched controls. Analysis of CYP17 and SULT1A1 genotypes were done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: The genetic polymorphisms of the estrogen-related genes SULT1A1(OR=2.5, 95% CI=1.28-4.98) and CYP17 (OR=4.1, 95= CI=1.78-9.63) were associated with an increased risk of breast cancer among postmenopausal women. Our data also showed evidence for the genetic regulation of serum 17 beta estradiol (E2) levels as measured by ELISA among the premenopausal women with a significant increase in the serum E2 level for the CYP17 A2 variants. CONCLUSION: These results suggest that both CYP17 and SULT1A1 genotypes could be important determinants of breast cancer risk in Indian women and may help in early identification of high risk subjects. Such genotype analysis resulting in a high-risk profile holds considerable promise for individualizing screening, diagnosis and therapeutic intervention in breast cancer.     

Relationship between CYP1A1 genetic polymorphisms and renal cancer in China

Aim: To study the potential role of cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms in the risk of renal cell cancer in Chinese. Methods: A total of 181 pathologically-proven renal cancers and 350 controls from the second Xiangya Hospital in Changsha were collected during the period from May 2007 to December 2010. CYP1A1 genetic polymorphisms were genotyped using PCR-RFLP. Unconditional logistic regression analysis was performed to analyze their relationship with risk of RCC. Results: Individuals with Val/Val genotypes had a significantly increased risk of RCC compared those with CYP1A1 IIe/IIe (OR=1.69, 95%CI=1.03-2.85). We also found CYP1A1 Wt/Vt and Vt/Vt to confer a significantly greater risk than CYP1A1 Wt/Wt (Wt/Vt: OR=2.14, 95%CI=1.24-3.45; Vt/Vt: OR=1.78, 95%CI=1.31-3.96). In smokers, a high increase risk of RCC was observed in those with CYP1A1 Val allele and Vt allele (Val allele: OR=2.13, 95%CI=1.40-2.57; Vt allele: OR=3.75, 95%CI=2.43-6.79), but no other significant interactions were found. Conclusion: Our study found suggestive evidence that CYP1A1 polymorphisms may play an important role in the etiology of RCC. Cigarette smoking may increase the susceptibility to RCC carcinogenesis in individuals with a high-risk genotype.     

CYP1A1和GSTM1基因多态性与内蒙古人群肺癌易感性的关系

背景与目的 肺癌是严重危害人类健康的恶性肿瘤之一，其发病与肺癌人群中某些肺癌相关基因的遗传多态性有关。本研究旨在探讨细胞色素P4501A1（CYP1A1）基因多态性和谷胱甘肽硫转移酶M1（GSTM1）基因多态性与内蒙古人群肺癌易感性的关系。方法 用PCR-RFLP技术分析了原发性肺癌组和住院对照组（各163例）的CYP1A1、GSTM1基因的多态性、基因型分布频率和交互作用。结果 CYP1A1突变型和GSTM1基因缺陷型EGSTM1（-）]频率分布分别为36．8％、65．0％（病例组）和19．0％、48．9％（对照组），二者经χ^2检验差异有显著性（χ^2=12．82，P=0．000；χ^2=9．78，P=0．002）。CYP1A1突变型患肺癌的风险显著增加（OR=2．48，95％CI为1．51～4．08）。GSTM1（-）者患肺癌的风险也显著增加（OR=2．03，95％CI为1．30～3．17）。基因突变的协同分析发现CYP1A1突变型／GSTM1（-）在肺癌组和对照组中的分布频率分别为28．8％和8．0％，二者经χ^2检验有显著性差异（χ^2=23．883，P=0．000）。CYP1A1突变型／GSTM1（-）患肺癌的风险显著增加（OR=4．90，95％CI为2．50～9．83）。无论是在肺癌组还是在对照组，CYP1A1突变型／GSTM1（-）和CYP1A1非突变型／GSTM1（-）在性别间分布频率的差异均无显著性（肺癌组χ^2=0．797，P=0．372；对照组χ^2=0．670，P=0．761）。吸烟与肺癌易感性的统计学分析，结果显示吸烟与肺癌易感性有关（χ^2=14．197，P=0．000），吸烟者患肺癌的风险显著增加（OR=2．33，95％CI为1.50～3．62）。CYP1A1突变型与吸烟关系的协同分析发现，携带CYP1A1突变型基因的吸烟者较携带CYP1A1突变型基因不吸烟者易患肺癌（OR=4．44，95％CI为2．40～8．32，χ^2=23．843，P=0．000）。GSTM1（-）与吸烟关系的协同分析中也发现，携带GSTM1（-）的吸烟者患肺癌的风险显著增加（OR=7．32，95％CI为3．39～15．50，χ^2=36．708，P=0．000）。结论 CYP1A1突变型和GSTM1（-）是内蒙古地区肺癌的易患因素，二者对肺癌的发生有协同作用，吸烟与肺癌的易感性也有关，CYP1A1突变型、GSTM1（-）与吸烟在肺癌的发生上也有相互促进作用。     

Functional evaluation of novel single nucleotide polymorphisms and haplotypes in the promoter regions of CYP1B1 and CYP1A1 genes

Interindividual variation in the expression of the carcinogen- and estrogen-metabolizing enzymes cytochrome P4501B1 and 1A1 (CYP1B1 and CYP1A1) has been detected in human lung. To search for polymorphisms with functional consequences for CYP1B1 and CYP1A1 gene expression, we examined 1.5 kb of the promoter region of each gene. Genomic DNA from 21 Caucasian individuals was amplified by polymerase chain reaction (PCR) for direct cycle sequencing. Eight single nucleotide polymorphisms (SNPs) for CYP1B1 and 13 SNPs for CYP1A1 were found. The majority of polymorphisms occurred as multiSNP combinations for individual subjects. The wild-type sequences were cloned into a luciferase reporter construct. The most frequent polymorphisms were then recreated by iterative site-directed mutagenesis, replicating single polymorphisms and multiSNP combinations. These wild-type and variant constructs were functionally evaluated in transient transfection experiments employing exposures to either the index polycyclic aromatic hydrocarbon (PAH) inducer benzo[a]pyrene (B[a]P), a composite mixture of cigarette smoke extract (CSE), or the repressor chemopreventive agent trans-3,4,5-trihydroxystilbene (reseveratrol). Results indicated that all wild-type and variant constructs responded in qualitatively concordant fashion to the inducers and to the repressor. The CYP1B1 haplotypes and the majority of CYP1A1 haplotypes were shown to have no functional consequence, as compared to those of the wild-type promoter sequences. Two constructs of composite polymorphisms of CYP1A1 appeared to result in a statistically significant increase in basal promoter activity (1.38- and 1.50-fold, respectively), but the degree of functional impact was judged unlikely to be biologically important in vivo. We conclude that the observed promoter region polymorphisms in these genes are common, but are of unclear functional consequence.     

CYP1A1 MspI and exon7 gene polymorphisms and lung cancer risk: An updated meta-analysis and review

Background

Many studies have examined the association between the CYP1A1 MspI and exon 7 gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent.

Methods

To assess this relationship more precisely, a meta-analysis and review were performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case-control studies published up to June 2010. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results

Ultimately, 64 studies, comprising 18,397 subjects from 49 case-control studies of the MspI genotype and 18,518 patients from 40 case-control studies of the exon 7 genotype, were included. A significantly elevated lung cancer risk was associated with 2 MspI genotype variants (for type C vs Type A: OR = 1.26, 95% CI = 1.12-1.42; for types B and C combined vs Type A: OR = 1.20, 95% CI = 1.13-1.28) in overall population. In the stratified analysis, a significant association was found in Asians, Caucasians, lung SCC, lung AC and Male population, not in mixed population, lung SCLC and Female population. However, inconsistent results were observed for CYP1A1 exon7 in our meta-analysis, two variants of the exon 7 polymorphism were associated with a significantly higher risk for lung cancer (for Val/Val vs Ile/Ile: OR = 1.24, 95% CI = 1.09-1.42; for (Ile/Val +Val/Val) vs Ile/Ile: OR = 1.15, 95% CI = 1.07-1.24) in overall population. In the stratified analysis, a significant assocation was found in Asians, Caucasians, lung SCC and Female population, not in mixed population, lung AD, lung SCLC and Male population. Additionally, a significant association was found in smoker population and not found in non-smoker populations for CYP1A1 MspI and exon7 gene.

Conclusions

This meta-analysis suggests that the MspI and exon 7 polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility and there is an interaction between two genotypes of CYP1A1 polymorphism and smoking, but these associations vary in different ethnic populations, histological types of lung caner and gender of case and control population.     

Clinical,Cytogenetic and CYP1A1 exon-1 Gene Mutation Analysis of Beedi Workers in Vellore Region,Tamil Nadu

Background: Beedi rollers are exposed to unburnt tobacco dust through cutaneous and pharyngeal route andit is extremely harmful to the body since it is carcinogenic in nature and can cause cancer during long exposure.This indicates that occupational exposure to tobacco imposes considerable genotoxicity among beedi workers.Materials and Methods: In the present study, 27 beedi workers and age and sex matched controls were enrolledfor clinical, cytogenetics and molecular analysis. Clinical features were recorded. The workers were in the agegroup of 28-67 years and were workers exposure from 8-60 years. Blood samples were collected from workersand control subjects and lymphocyte cultures were carried out by using standard technique, slides were preparedand 50 metaphases were scored for each sample to find the chromosomal abnormalities. For molecular analysisthe genomic DNA was extracted from peripheral blood, to screen the variations in gene, the exon 1 of CYP1A1gene was amplified by polymerase chain reaction (PCR) and then screened with Single Strand ConformationPolymorphism (SSCP) analysis. Results: A statistically significant increase was observed in the frequencies ofchromosomal aberrations in exposed groups when compared to the respective controls and variations observedin Exon 1 of CYP1A1(Cytochrome P450, family 1, subfamily A, polypeptide 1) gene. Conclusions: This studyshows that, the toxicants present in the beedi that enter into human body causes disturbance to normal stateand behavior of the chromosomes which results in reshuffling of hereditary material causing chromosomalaberrations and genomic variations.     

Effects of functional genetic polymorphisms in the CYP19A1 gene on prostate cancer risk and survival

CYP19 catalyzes the conversion of androgens to estrogens and is a critical enzyme affecting the sex hormone milieu. In this study, we investigated the functions of CYP19A1 polymorphisms and their associations with prostate cancer risk and clinical outcome. This case‐control study evaluated the effects of three single nucleotide polymorphisms (SNPs) in CYP19A1 on the risk of prostate cancer in 330 prostate cancer patients and 354 normal controls. The associations between each SNP and sex hormone levels were evaluated in 164 healthy male patients. The functions of the SNPs were determined by reporter gene assays in PC3 and DU145 cell lines. Prostate‐specific antigen nadir was evaluated in 142 patients with metastatic prostate cancer treated with androgen deprivation therapy. Cancer‐specific survival (CSS) was determined in 166 patients with metastatic prostate cancer, to evaluate the influence of the three SNPs. Each variant allele of the three SNPs significantly decreased the risk of prostate cancer. Haplotype analysis showed that the T‐A‐G haplotype (corresponding to rs2470152‐rs10459592‐rs4775936) increased the risk of prostate cancer, while the C‐C‐A haplotype decreased the risk. The estrone/androstenedione ratio was significantly higher in men with the C allele of rs2470152, the C allele of rs10459592, and the A allele of rs4775936 in a gene‐dosage‐dependent manner. Patients with the variant allele at rs4775936 had significantly shorter CSS. These results indicate that CYP19A1 polymorphisms may influence prostate cancer risk and survival by modifying promoter activity, with subsequent effects on the sex hormone milieu.     

Lack of Association Between the CYP1A1 Ile462Val Polymorphism and Endometrial Cancer Risk: a Meta-analysis

Purpose: Any association between the CYP1A1 Ile462Val polymorphism and endometrial cancer risk remainsinconclusive. For a more precise estimate, we performed the present meta-analysis. Methods: PUBMED, OVIDand EMBASE were searched for the studies which met inclusion criteria. Data in all eligible studies wereevaluated and extracted by two authors independently. The meta-analysis estimated pooled odds ratio (OR) with95% confidence interval (CI) for endometrial cancer risk attributable to the CYP1A1 Ile462Val polymorphism.Results: A total of 7 studies were included in this meta-analysis. The results indicated no association betweenendometrial cancer risk and the CYP1A1 Ile462Val polymorphism (for Val vs Ile allele model [OR 1.09, 95%CI 0.73-1.62]; for Val.Val vs Ile.Ile genotype model [OR 1.54, 95% CI 0.56-4.23]; for (Ile.Val + Val.Val) vs Ile.Ilegenotpye model [OR 1.08, 95% CI 0.71-1.63]; for Val.Val vs (Ile.Ile + Ile.Val) genotype model [OR 1.46, 95% CI0.53-4.04]). Conclusions: This meta-analysis suggests that there is no association between endometrial cancerrisk and the CYP1A1 Ile462Val polymorphism.