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1.
目的:探讨TOX3基因单核苷酸多态与中国北方汉族绝经前妇女乳腺癌风险的关系。方法:采用多重单碱基延伸单核苷酸多态性分型技术(Snapshot)分析方法,检测280例绝经前的乳腺癌患者和287例绝经前的正常对照者TOX3基因rs3803662和rs12443621多态性位点基因型,并比较不同基因型与乳腺癌风险的关系。结果:TOX3基因rs3803662和rs12443621多态性位点基因型频率,在乳腺癌病例组和对照组之间差异无统计学意义,P值分别为0.718和0.340。Logistic回归分析结果显示,对于rs3803662位点,与GG基因型相比,GA、AA和GA+AA基因型与乳腺癌的危险性无关(OR=0.846,95%CI:0.489~1.463,P=0.549;OR=0.802,95%CI:0.470~1.368,P=0.418;OR=0.821,95%CI:0.492~1.368,P=0.449);对于rs12443621位点,与GG基因型相比,GA、AA和GA+AA基因型与乳腺癌的危险性无关(OR=0.755,95%CI:0.518~1.099,P=0.755;OR=0.850,95%CI:0.528~1.368,P=0.504;OR=0.781,95%CI:0.548~1.112,P=0.170)。结论:在目前样本条件下,TOX3基因rs3803662和rs12443621位点多态性与中国北方汉族绝经前妇女乳腺癌易感性之间无明显关联。 相似文献
2.
目的:探讨MAP3K1及LSP1基因单核苷酸多态与中国北方汉族绝经前妇女乳腺癌风险的关系。方法:采用多重单碱基延伸单核苷酸多态性分型技术(Snapshot)分析方法,检测280例绝经前乳腺癌患者和287例绝经前正常对照者MAP3K1基因rs889312和LSP1基因rs3817198多态性位点基因型,并比较不同基因型与乳腺癌风险的关系。结果:MAP3K1基因rs889312和LSP1基因rs3817198多态性位点基因型频率在乳腺癌和对照样本之间未存在显著差异(P=0.937、P=0.323)。Logistic回归分析结果显示,对于MAP3K1的rs889312位点,与AA携带者相比,AC携带者、CC携带者和AC+CC基因型携带者与乳腺癌的患病危险无关(OR=0.814,95%CI=0.537-1.236,P=0.335;OR=0.999,95%CI=0.627-1.594,P=0.998;OR=0.876,95%CI=0.591-1.298,P=0.509);对于LSP1的rs3817198位点,与TT携带者相比,CT携带者、CC携带者和CT+CC基因型携带者与乳腺癌的患病危险无关(OR=0.832,95%CI=0.565-1.223,P=0.349;OR=0.651,95%CI=0.108-3.936,P=0.640;OR=0.839,95%CI=0.573-1.229,P=0.369)。结论:上述两个基因MAP3K1和LSP1位点多态性与中国北方汉族绝经前妇女乳腺癌易感性之间无明显相关性。 相似文献
3.
目的:探讨BRCA2基因单核苷酸多态性(SNP)与江西汉族女性散发性乳腺癌易感性的关系。方法:利用SequenomMassArrayiPLEX GOLD系统对江西南昌大学第一附属医院散发性乳腺癌患者152例和健康对照组165名的BRCA2基因编码区3个单核苷酸多态性位点(rs766173,rs144848,rs1801426)进行基因型检测,非条件Logistic回归分析。结果:rs766173位点基因型和等位基因型频率分布差异均有统计学意义(χ2=4.602,P=0.032;χ2=4.097,P=0.043)。相对TT基因型,TG杂合型与TG+GG型均能显著性增加乳腺癌发生的危险性,OR值(95%CI)分别为1.971(1.060~3.666)和1.934(1.052~3.555),P分别为0.032和0.034。相对等位基因T,等位基因G为易感等位基因,OR值为1.792(95%CI=1.012~3.172,P=0.045)。另外两个位点rs144848和rs1801426多态性分布频率在乳腺癌组和对照组之间差异无统计学意义。结论:rs766173位点基因多态性与江西地区汉族女性散发性乳腺癌易感性相关,另外两个多态性位点rs144848和rs1801426与江西地区女性散发性乳腺癌易感性无关。 相似文献
4.
背景与目的:乳腺癌作为中国女性最常见的恶性肿瘤,每年的新发数量和死亡数量分别占全世界的12.2%和9.6%,但与中国乳腺癌患者明显相关的基因多态位点至今尚不清楚。本研究旨在探讨2q35 rs13387042和8q24 rs13281615单核苷酸多态性与中国北方汉族绝经前妇女乳腺癌风险关系,为预防和治疗乳腺癌提供循证依据。方法:采用多重单碱基延伸单核苷酸多态性分型技术(SNaPshot)分析方法,检测了280例绝经前乳腺癌患者和287例绝经前正常对照者2q35 rs13387042和8q24 rs13281615多态性位点基因型,并比较不同基因型和等位基因与乳腺癌风险的关系。结果:2q35 rs13387042多态性位点基因型频率在乳腺癌和对照样本之间差异有统计学意义(P=0.017);8q24 rs13281615多态性位点基因型频率在乳腺癌和对照样本之间差异无统计学意义(P=0.967)。Logistic回归分析结果显示,对于2q35 rs13387042位点,与GG相比,GA和GA+AA基因型携带者显著增加乳腺癌的患病风险(OR=1.793,95%CI:1.177~2.733,P=0.007;OR=1.691,95%CI:1.122~2.550,P=0.012),而AA携带者与乳腺癌的患病风险无关(OR=0.572,95%CI:0.104~3.153,P=0.521);与G等位基因相比,A等位基因显著增加乳腺癌的患病风险(OR=1.505,95%CI:1.033~2.193,P=0.033)。对于8q24rs13281615位点,与AA相比,AG、GG和AG+GG基因型携带者与乳腺癌的患病风险无关(OR=0.992,95%CI:0.660~1.490,P=0.968;OR=1.047,95%CI:0.642~1.708,P=0.853;OR=1.007,95%CI:0.682~1.487,P=0.971);与A等位基因相比,G等位基因不增加乳腺癌患病风险(OR=1.021,95%CI:0.809~1.288,P=0.863)。结论:本实验证实2q35 rs13387042多态性位点能够增加中国北方汉族绝经前妇女乳腺癌易感风险,而8q24 rs13281615多态性位点与中国北方汉族绝经前妇女乳腺癌易感性无明显相关性。 相似文献
5.
目的:探讨中国西北地区汉族妇女脱嘌呤/脱嘧啶核酸内切酶1(APE1)单核苷酸多态性与卵巢癌易感性的关系.方法:采用病例对照研究,应用PCR及直接测序法检测116例卵巢癌患者及141例健康妇女APE1位点rs1760944和rs1130409的单核苷酸多态性(SNP).结果:rs1130409位点的TG和GG基因型相对于TT基因型,降低了患卵巢癌的风险.进一步分析发现等位基因G相对于等位基因T,显著降低患卵巢癌的风险.按年龄、初潮年龄、孕次、产次、是否绝经进行分层分析,发现rs 1130409的TG/GG基因型比TT基因型在年龄≥50岁、初潮年龄≥15岁、孕次≥3次、产次≥3次和已绝经的女性中的保护作用更加显著.但是,未发现rs1760944的多态性与卵巢癌易感性相关.单倍体分析中,APE1T/G和G/G单倍体相对于T/T单倍体降低患卵巢癌风险.结论:APE1基因单核苷酸多态性与中国西北地区汉族妇女卵巢癌易感性密切相关. 相似文献
6.
[目的]探讨CAV-1基因多态性与散发乳腺癌的相关性。[方法]采用病例对照研究,纳入经病理确诊的135例女性乳腺癌患者作为实验组,166例女性健康体检者为对照组。通过竞争性等位基因特异性PCR法对研究对象基因位点进行分型;采用χ2检验比较CAV-1各SNP基因型及等位基因频率在两组中的分布差异;非条件Logistic回归分析CAV-1基因多态性与乳腺癌易感性的关联。[结果]在共显性模型、显性模型及等位基因模型下rs3807987及rs7804372位点多态性与乳腺癌易感性密切相关。rs3807987:相对于GG基因型,AG、AA基因携带者(AG/AA基因型)均增加乳腺癌的发病风险(P<0.05),OR值分别为2.110(95%CI:1.270~3.505)、1.968(95%CI:1.205~3.216)。rs7804372位点:相对于TT基因型,AT、AA基因携带者(AT/AA基因型)均增加乳腺癌的发病风险(P<0.05),OR值分别为2.088(95%CI:1.285~3.392)、2.059(95%CI:1.293~3.280)。rs12672038位点:在共显性模型、显性模型、等位基因模型均未见rs12672038位点多态性分布与乳腺癌发病风险之间存在相关性。[结论]CAV-1基因rs3807987与rs7804372多态性与乳腺癌易感性相关。 相似文献
7.
目的:探讨MKK4基因-1304T>G位点单核苷酸多态基因型在中国东部人群中的分布及其对食管癌易感性的影响。方法:设计以医院为基础的病例对照研究,进行食管癌患者与对照人群频数匹配,采用聚合酶链反应-限制性片段长度多态性的方法(PCR-RFLP)对571例食管癌患者和785名正常人的MKK4基因-1304T>G位点(rs3826392)进行基因分型。利用Logistic回归分析基因多态性与食管癌发病风险的关联,并校正年龄和性别。结果:MKK4基因-1304T>G位点基因多态性在病例和对照组中分布差异无统计学意义,GG基因型(OR=0.98,95%CI:0.67~1.61),TG基因型(OR=1.12,95%CI:0.90~1.43),P=0.435。结论:MKK4基因-1304T>G位点的单核苷酸多态可能与中国东部人群食管癌易感性无关。 相似文献
8.
目的:探讨let-7靶基因KRAS结合区rs712多态性在脑胶质瘤患者和健康对照人群中的分布及与脑胶质瘤临床特征的相关性。方法:采用聚合酶链反应-限制性片段长度多态性检测153例脑胶质瘤患者(脑胶质瘤组)和204例健康人群(对照组)KRAS rs712多态性。结果:对照组中GG、GT和TT基因型频率分别为67.2%、29.9%和2.9%;脑胶质瘤组中各基因型频率分别为54.2%、36.6%和9.2%。与GG基因型相比,TT和GT/TT基因型显著增加了脑胶质瘤的发病风险,TT与GG相比,χ2=7.93,OR=3.85,95%CI为1.43~10.41,P=0.005;GT/TT与GG相比,χ2=6.16,OR=1.73,95%CI为1.12~2.66,P=0.013。对照组中G和T等位基因频率分别为82.1%和17.9%;脑胶质瘤组中分别为72.5%和27.5%。与G等位基因相比,T等位基因显著增加了脑胶质瘤的发病风险,χ2=9.31,OR=1.74,95%CI为1.22~2.48,P=0.002。根据脑胶质瘤临床病理分级进行亚组分析发现,GT/TT基因型和T等位基因在Ⅲ~Ⅳ级脑胶质瘤患者的频率均显著高于在Ⅰ~Ⅱ级患者中的频率。GT/TT与GG相比,χ2=4.40,OR=1.99,95%CI为1.04~3.81,P=0.036;T与G相比,χ2=5.51,OR=1.83,95%CI为1.10~3.04,P=0.019。结论:KRAS rs712等位基因多态性可能是脑胶质瘤的易感因素。 相似文献
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目的:探讨DNA修复基因(ERCC1、ERCC2、XRCC1)单核苷酸多态性对胃癌患者卡培他滨联合奥沙利铂化疗敏感性的相关性.方法:本回顾性研究选取XELOX作为一线化疗方案的100例晚期胃癌患者为研究对象,检测分析三个基因六个单核苷酸多态性位点(ERCC1 rs11615;ERCC2 rs13181,rs1799793;XRCC1 rs25487,rs25489,rs1799782),同时分析其与临床预后的关系.结果:XRCC1 rs25487的A/G等位基因频率、AG/AA/GG基因分布频率均与疾病化疗敏感性和无进展生存期有关,携带GG基因型患者疗效好(P<0.05),中位PFS为8.00个月(95%CI:6.34~9.66);ERCC2 rs13181的G/T等位基因频率、GG/GT/TT基因分布频率与疾病化疗敏感性和无进展生存期明显相关,携带TT基因型患者疗效好(P<0.05),中位PFS为7.46个月(95%CI:6.45~8.48).COX比例风险模型显示ERCC2 rs13181 G/T基因型是晚期胃癌无进展生存期的独立风险因素之一(HR=0.72,95%CI:0.53~0.97,P=0.025).结论:ERCC2 rs13181基因多态性可能是评估接受XELOX化疗晚期胃癌患者预后的关键指标. 相似文献
11.
Dai H Zhang L Cao M Song F Zheng H Zhu X Wei Q Zhang W Chen K 《Breast cancer research and treatment》2011,127(2):531-540
Disruption of the circadian rhythm or biological clock, which is regulated by a number of clock genes, including circadian
locomotor output cycles kaput (CLOCK), period genes (PERs), and cryptochrome genes (CRYs), is a risk factor for breast cancer. We hypothesized that genetic variation in these clock genes may influence breast cancer
risk. To test this hypothesis, we designed a hospital-based study that included 1,538 breast cancer patients and 1,605 healthy
controls. We genotyped subjects for five single nucleotide polymorphisms (SNPs) and a length variant of the circadian clock
genes and evaluated their associations with breast cancer risk. These polymorphisms were determined by TaqMan allelic discrimination
assays and the polymerase chain reaction-restriction fragment length polymorphism method. Univariate logistic regression analysis
showed that polymorphisms of the CLOCK and CRY1 genes were associated with breast cancer risk. We found that carriers of the CLOCK CT and combined CT+TT genotypes had a significantly higher risk of breast cancer than carriers of the CC genotype (aOR = 1.35,
95% CI = 1.12-1.63 and aOR = 1.30, 95% CI = 1.09–1.56, respectively). Carriers of the CRY1 GT genotype had a decreased risk of breast cancer (aOR = 0.84, 95% CI = 0.71–0.99). We also observed a lower risk of breast
cancer in carriers of the CRY2 CC genotype who were ER-positive than in those who were ER-negative (OR = 0.15, 95% CI = 0.04–0.67). When stratified by
the CLOCK genotype, patients with the CLOCK CT/
CRY2 CC genotypes had significantly lower cancer risk than those with the GG genotype (aOR = 0.36, 95% CI = 0.14–0.95). Individuals
carrying both the CLOCK CC and PER2 AA genotypes had an increased cancer risk (aOR = 2.28, 95% CI = 1.22–4.26). Our study suggests that genetic variants of the
circadian rhythm regulatory pathway genes contribute to the differential risk of developing breast cancer in Chinese populations. 相似文献
12.
Head and neck squamous cell carcinoma (HNSCC) means a group of cancers developed from the upper aerodigestive tract, and 90%
of them are squamous cell carcinomas. HNSCC is the tenth most commonly diagnosed form of cancer in males worldwide, but it
is the seventh most common cause of cancer-related death. The circadian clock regulates daily rhythmic variations in various
physiologic processes including sleep and activity, appetite, hormone levels, metabolism, and gene expression. Many recent
studies have demonstrated that the disruption of circadian rhythm is associated with cancer development and tumor progression,
such as chronic myeloid leukemia, hepatocellular carcinoma, endometrial carcinoma, and breast cancer. However the direct links
between aberrant circadian clock gene expression and human malignancies, including HNSCC, remain largely unknown. In this
study, the expression profiles of nine circadian clock genes of cancer tissue and noncancerous part from 40 patients of HNSCC
were investigated. The expression of PER1, PER2, PER3, CRY1, CRY2, CKIε, and BMAL1 showed significant downregulation in the cancer tissues (p < 0.005). Downregulated PER3, CRY2, and BMAL1 expression was correlated with more advanced cancer stages (p < 0.05). Downregulated PER3 and upregulated TIM expression correlated with larger tumor size (p < 0.05), and lower expression of PER3 correlated with deeper tumor invasion (p < 0.05). Poor survival was related to lower expression of PER1 (p < 0.05) and PER3 (p < 0.01). These results indicate a possible association of circadian clock gene, especially PER3, expression with the pathogenesis of HNSCC. 相似文献
13.
Disruption of circadian rhythm may be a risk factor in the development of breast cancer, but molecular changes in circadian rhythm controlled genes in breast cancer cells are still unexplored. We used immunohistochemical staining, methylation specific PCR and direct sequencing methods to analyze molecular changes in three most important genes, namely PER1, PER2 and PER3, in circadian rhythm in 55 cases of breast cancer of Taiwanese women. Our results reveal disturbances in the expression of the three period (PER) genes in most (>95%) of the breast cancerous cells in comparison with the nearby non-cancerous cells. The PER gene deregulation is not caused by genetic mutations but most probably by methylation of the PER1 or PER2 promoter. Methylation of the PER gene promoters has a strong correlation with c-erbB2 expression (P = 0.017). Since the circadian clock controls expression of cell-cycle related genes, we suggest that disturbances in PER gene expression may result in disruption of the control of the normal circadian clock, thus benefiting the survival of cancer cells and promoting carcinogenesis. Differential expression of circadian genes in non-cancerous and cancerous cells may provide a molecular basis for chronotherapy of breast cancer. 相似文献
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Methylation of CpG dinucleotides in the promoter sequence of a gene can lead to deregulated and suppressed gene expression. In this study, we have developed procedures for methylation-specific polymerase chain reaction (MSP) and sequencing analysis to determine CpG methylation status of the promoter sequences of nine circadian genes in 35 endometrial cancers (EC) and paired noncancerous endometrial tissues. DNA methylation was found in the promoter sequences of PER1, PER2, and CRY1, but not of other six circadian genes in the ECs and normal tissues examined. Eleven of the 35 EC tissues showed CpG methylation in the promoter sequences of PER1, PER2, or CRY1. Of these 11 cases, 1 had promoter methylation in all the three genes, 1 in PER1 and PER2, 3 in PER1 and CRY1, and 6 in PER1, respectively. In comparison, promoter CpG methylation of PER1, PER2, or CRY1 was found in only 7 of 35 paired noncancerous tissues including 2 in PER1 and PER2, 2 in PER1, and 3 in CRY1. In summary, promoter methylation in the PER1, PER2, or CRY1 circadian genes was detected in about one-third of EC and one-fifth of noncancerous endometrial tissues of 35 paired specimens indicating possible disruption of the circadian clock in the development of EC. 相似文献
16.
Breast cancer is already the most common malignancy affecting women worldwide, and evidence is mounting that breast cancer induced by circadian disruption (CD) is a warranted concern. Numerous studies have investigated various aspects of the circadian clock in relation to breast cancer, and evidence from these studies indicates that melatonin and the core clock genes can play a crucial role in breast cancer development. Even though epigenetics has been increasingly recognized as a key player in the etiology of breast cancer and linked to circadian rhythms, and there is evidence of overlap between epigenetic deregulation and breast cancer induced by circadian disruption, only a handful of studies have directly investigated the role of epigenetics in CD-induced breast cancer. This review explores the circadian clock and breast cancer, and the growing role of epigenetics in breast cancer development and circadian rhythms. We also summarize the current knowledge and next steps for the investigation of the epigenetic link in CD-induced breast cancer. 相似文献
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Circadian rhythms regulate diverse physiological processes including homeostatic functions of steroid hormones and their receptors. Estrogen receptor-alpha (ERalpha) is essential for normal mammary gland physiology and is a prognostic marker for the treatment of breast cancer. We report that Per2, a core clock gene, links the circadian cycle to the ERalpha signaling network. Binding of enhances ERalpha degradation, while suppression of Per2 levels leads to ERalpha stabilization. In turn, Per2 itself is estrogen inducible in these cells, suggesting a feedback mechanism to attenuate stimulation by estrogen. In addition, overexpression of Per2 in breast cancer cells leads to significant growth inhibition, loss of clonogenic ability and apoptosis. Taken together, these results further support a critical role for peripheral circadian regulation in tissue homeostasis and suggest a novel role for clock genes in estrogen receptor-positive breast cancer. 相似文献
19.
Expression of the Circadian Clock Genes Per1 and Per2 in Sporadic and Familial Breast Tumors
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Sherry L Winter Lucine Bosnoyan-Collins Dushanthi Pinnaduwage Irene L Andrulis 《Neoplasia (New York, N.Y.)》2007,9(10):797-800
There is a growing body of evidence implicating aberrant circadian clock expression in the development of cancer. Based on our initial experiments identifying a putative interaction between BRCA1 and the clock proteins Per1 and Per2, as well as the reported involvement of the circadian clock in the development of cancer, we have performed an expression analysis of the circadian clock genes Per1 and Per2 in both sporadic and familial primary breast tumors and normal breast tissues using real-time polymerase chain reaction. Significantly decreased levels of Per1 were observed between sporadic tumors and normal samples (P < .00001), as well as a further significant decrease between familial and sporadic breast tumors for both Per1 (P < .00001) and Per2 (P < .00001). Decreased Per1 was also associated with estrogen receptor negativity (53% vs 15%, P = .04). These results suggest a role for both Per1 and Per2 in normal breast function and show for the first time that deregulation of the circadian clock may be an important factor in the development of familial breast cancer. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis, potentially promoting carcinogenesis. 相似文献
20.
Artificial Lighting in the Industrialized World: Circadian Disruption and Breast Cancer 总被引:1,自引:0,他引:1
Stevens RG 《Cancer causes & control : CCC》2006,17(4):501-507
Breast cancer risk is high in industrialized societies, and increases as developing countries become more Westernized. The
reasons are poorly understood. One possibility is circadian disruption from aspects of modern life, in particular the increasing
use of electric power to light the night, and provide a sun-free environment during the day inside buildings. Circadian disruption
could lead to alterations in melatonin production and in changing the molecular time of the circadian clock in the suprachiasmatic
nuclei (SCN). There is evidence in humans that the endogenous melatonin rhythm is stronger for persons in a bright-day environment
than in a dim-day environment; and the light intensity necessary to suppress melatonin at night continues to decline as new
experiments are done. Melatonin suppression can increase breast tumorigenesis in experimental animals, and altering the endogenous
clock mechanism may have downstream effects on cell cycle regulatory genes pertinent to breast tissue development and susceptibility.
Therefore, maintenance of a solar day-aligned circadian rhythm in endogenous melatonin and in clock gene expression by exposure
to a bright day and a dark night, may be a worthy goal. However, exogenous administration of melatonin in an attempt to achieve
this goal may have an untoward effect given that pharmacologic dosing with melatonin has been shown to phase shift humans
depending on the time of day it’s given. Exogenous melatonin may therefore contribute to circadian disruption rather than
alleviate it.
Supported by grant ES11659 from the National Institute of Environmental Health Sciences. 相似文献