FGFR2基因多态性与乳腺癌的相关性研究

目的:探讨成纤维细胞生长因子受体2基因(FGFR2)第二内含子单核苷酸多态性在女性群体中的频率分布及其与女性乳腺癌易感性之间的相关性.方法:运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法结合琼脂糖凝胶电泳技术,对106例女性乳腺癌患者(乳腺癌组)和116例正常女性(对照组)对照进行检测,分析两组贵州地区人群FGFR2基因第二内含子的两个单核苷酸多态性位点rs2420946和rs2981579的基因及基因型的分布情况.结果:乳腺癌组FGFR2基因单核苷酸多态性位点rs2420946的基因型(AA,AG.CG)频率分别为15.09%、48.11%、36.79%,对照组为18.10%、43.97%、37.93%;乳腺癌组与对照组A等位基因频率分别为39.15%和40.09%,G等位基因频率分别为60.85%和59.91%;两组人群分别进行比较,基因型及等位基因频率分布的差异均无统计学意义(P>0.05);FGFR2基因rs2981579的基因型(CC,CT,TT)频率在乳腺癌组分别为30.19%、45.28%、24.53%,对照组为27.59%、48.28%、24.14%;乳腺癌组与对照组c等位基因频率分别为52.83%和51.72%,T等位基因频率分别为47.17%和48.28%;两组人群分别进行比较,基因型频率与等位基因频率分布的差异均无统计学意义(P>0.05).结论:FGFR2基因第二内含子的两个单核苷酸多态性位点rs2420946及rs2981579在乳腺癌及对照人群中基因型频率与等位基因频率分布差异均无统计学意义,提示两个位点的多态性与乳腺癌无明显相关性.     

湖北地区人群乳腺癌易感基因FGFR2多态性研究

目的:探讨湖北地区人群成纤维细胞生长因子受体-2基因(FGFR2)第2内含子单核苷酸多态性(SNP)与乳腺癌易感性的关系。方法:采用PCR及DNA测序方法,对汉族204例女性乳腺癌患者(乳腺癌组)和192名正常女性(对照组)FGFR2基因第2内含子区的2个多态性位点(rs2981582和rs10510097)进行分析,计算基因型和等位基因频率。结果:汉族人群正常对照组FGFR2基因第2内含子SNP位点rs2981582的C/C、C/T和T/T基因型频率分别为31.82%、54.54%和13.64%,而乳腺癌组分别为34.02%、53.61%和12.37%,其基因型和等位基因频率两组相比差异均无统计学意义,P值均>0.05;另一位点rs10510097正常对照组的C/C、C/T和T/T基因型频率分别为60.00%、33.33%和6.67%,乳腺癌组分别为55.31%、36.87%和7.82%,其基因型和等位基因频率两组相比差异均无统计学意义,P值均>0.05。结论:湖北地区人群FGFR2第2内含子2个多态性位点和乳腺癌并无明显相关性。     

中国人群FGFR2基因多态性与乳腺癌易感相关性研究的Meta分析

目的系统评估成纤维细胞生长因子受体2(fibroblast growth factor receptor 2,FGFR2)基因内含子的3个单核苷酸位点rs2981582、rs1219648和rs2420946多态性与中国人群乳腺癌的易感性的关系。方法计算机检索PubMed、Embase、Cochrane library、中国知网、维普、万方数据库及中国生物医学文献数据库中,2014-06-01之前关于FGFR2基因内含子的3个单核苷酸位点rs2981582、rs1219648和rs2420946多态性与中国人群乳腺癌易感性的相关研究,按纳入与排除标准筛选文献、提取资料并评价纳入研究的质量后,采用Stata 12.0软件进行Meta分析,计算合并OR值及其95%CI,并进行发表偏倚评估及敏感性分析。结果共纳入18篇文献,包括14 568例患者和12 864名对照。Meta分析结果显示,FGFR2rs2981582、rs1219648和rs2420946基因多态性与中国人群乳腺癌有显著相关性。以地域进行亚组分析,rs2981582的T等位基因在南方人群(OR=1.13,95%CI:1.06~1.22,P=0.001)和北方人群(OR=1.26,95%CI:1.06~1.49,P=0.008)中与乳腺癌显著相关;rs2420946的T等位基因在南方人群(OR=1.15,95%CI:1.08~1.23,P<0.05)中与乳腺癌显著相关,北方人群中差异无统计学意义(OR=1.03,95%CI:0.87~1.22,P=0.695);rs1219648的G等位基因在南方人群(OR=1.19,95%CI:1.10~1.28,P<0.05)和北方人群(OR=1.17,95%CI:1.00~1.37,P=0.05)中与乳腺癌有显著相关。结论 FGFR2rs2981582、rs1219648和rs2420946基因多态性与中国人群乳腺癌易感性显著相关,但以地域进行亚组分析时则表现有差异。     

TNRC9和FGFR2基因多态性与湖北地区汉族人群乳腺癌患病风险研究

目的:研究探讨TNRC9基因rs3803662和FGFR2基因rs17102287单核苷酸多态性(SNP)及两SNP连锁与湖北地区汉族妇女乳腺癌易感性的关系.方法:抽取汉族510例乳腺癌患者和550例健康妇女外周血,分离淋巴细胞,抽提基因组DNA,检测TNRC9 rs3803662和FGFR2 rs17102287 的基因多态性,计算基因型和等位基因频率,研究各基因型以及基因SNP连锁之间对乳腺癌风险的影响.结果:TNRC9基因SNP位点rs3803662的C/C、C/T和T/T基因型频率在病例组和对照组分别为13.0％、46.4％、40.6％和7.3％、52.1％、40.6％,其基因型频率相比差异有统计学意义,x2=9.40,P=0.043.而等位基因频率两组相比差异均无统计学意义;FGFR2基因SNP位点rs17102287的C/C、C/T和T/T基因型频率在病例组和对照组中差异无统计学意义;等位基因频率两组相比差异无统计学意义.两基因连锁分析D'=0.087,r2=0.085,没有明显连锁不平衡现.结论:TNRC9基因rs3803662多态性与汉族妇女乳腺癌易感性有关,FGFR2基因rs17102287多态性及其与TNRC9基因rs3803662单倍体连锁与湖北地区汉族人群妇女乳腺癌易感性无相关性.     

FGFR2 基因多态性与乳腺癌易感性的相关性研究*

目的:探讨纤维细胞生长因子受体2（FGFR 2）基因rs 2981582 位点单链核苷酸多态性与中国女性乳腺癌易感性之间的关系。方法:利用Tm-shifting 实时荧光定量PCR 检测FGFR2 基因rs 2981582 位点SNP（C/T）,用荧光染料SYBR GreenⅠ标记样本DNA,通过在特异引物5' 端加上不同长度的尾,使不同基因型溶解曲线的峰值出现差异。确定判断标准:Tm≤84.6℃的是纯合子CC,≥87.5℃的是纯合子TT,处于中间的是杂合子TC。利用此方法对956 例乳腺癌患者和471 例良性乳腺疾病患者进行病例对照研究,分析FGFR2 基因rs 2981582 位点SNP 与乳腺癌发生之间的关系。结果:对照组CC、CT、TT各基因型表达的例数及基因频率分别为234 例（49.68%）、181 例（38.43%）、56例（11.89%）。 乳腺癌组总体各基因型例数及基因频率分别为426 例（44.56%）、400 例（41.84%）、130 例（13.60%）,与对照组比较无统计学意义（P=0.183）。 进一步分层分析发现,ER（+）组各基因型例数及基因频率分别为189 例（41.27%）、202 例（46.12%）、67例（14.63%）,与对照组比较有统计学意义（P=0.035）;而ER（-）组各基因型及基因频率分别为237 例（47.59%）、198 例（39.75%）、63例（12.65%）,与对照组比较无统计学意义（P=0.802）。 结论:FGFR2 基因第二内含子SNP rs 2981582 与ER阳性乳腺癌的发生有显著关系,同时验证了用本方法检测大批量人群标本的SNP 操作简便,检测耗时短,结果特异且费用较为低廉,适合于进行大规模样品的SNP 快速测定。      

FGFR1基因单核苷酸多态性与中国北方汉族女性乳腺癌发病风险及临床病理特征的关系

目的:探究成纤维生长因子受体1（fibroblast growth factor receptor-1,FGFR1)基因单核苷酸多态性与中国北方汉族女性乳腺癌发病风险和临床病理特征的相关性。方法:采用多重单碱基延伸单核苷酸多态性分型技术检测747例乳腺癌患者和716例健康女性人群FGFR1基因rs13317和rs3213849多态位点基因型,并比较不同基因型与乳腺癌发病风险和临床病理特征的关系。结果:FGFR1基因rs13317和rs3213849多态位点基因型频率在乳腺癌组和对照组中的分布无统计学差异(P＞0.05)。与TT基因型携带者相比,rs13317位点的CT基因型、CC基因型和CT+CC基因型携带者与乳腺癌发病风险无关(P=0.464、P=0.136、P=0.103)。与GG基因型携带者相比,rs3213849位点的GA基因型、AA基因型和GA+AA基因型携带者与乳腺癌发病风险无关(P=0.642、P=0.222、P=0.416)。临床病理分析结果显示,rs13317位点多态性与乳腺癌患者的临床分期、肿瘤大小、组织学分级、淋巴结转移、ER、PR、HER2、Ki67及p53无关(P＞0.05)。在共显性模型下,rs3213849位点在Ki67分布上可能存在差异(P=0.055);在显性模型下,rs3213849位点与Ki67表达情况具有相关性(P=0.023),与其他临床病理因素之间均不相关(P＞0.05)。结论:在目前的样本条件下,FGFR1基因rs3213849位点与Ki67表达可能相关,而rs13317和rs3213849多态性与中国北方汉族女性乳腺癌易感性及其他临床病理特征之间无明显相关性。     

ZO-1 SNPs与胃癌遗传易感性及预后*

目的:探讨中国福建地区汉族人群中ZO- 1 基因TJP1 4 个已知位点单核苷酸多态性（SNPs）与胃癌遗传易感性及进展和预后的相关性。方法:应用PCR-LDR法检测福建医科大学附属第一医院200 例健康体检个体及220 例原发性胃腺癌患者TJP1基因4 个SNP 位点的基因型。结果:福建地区汉族人群中,TJP-1 SNP rs 7179270 位点稀有等位基因C 的频率为0.2,而其他三个位点（rs 34771010,rs 28578444和rs 41280058）稀有等位基因频率为0.0。TJP1 基因SNP 位点rs 7179270 200 例对照组等位基因C、T 的频率分别为20% 和80% ,胃癌病例组等位基因C、T 的频率为32.6% 和67.4% ;CC、C/T和TT的基因型频率在对照组分别为4% 、32%和64% ,而在病例组为10.9% 、43.2% 和45.9% ,差异具有统计学意义（OR= 1.953,95%CI 1.425～2.677,P<0.001）。 TJP1 rs 7179270位点基因型与胃癌患者的性别、年龄、分化程度、浸润深度、淋巴结转移及手术后生存时间无显著相关（P>0.05）。 结论:TJP1rs 7179270 位点携带等位基因C 的CC和C/T基因型个体的胃癌患病风险提高,提示检测该位点基因型有助于评估胃癌的遗传易感性;TJP1 rs 7179270 位点的基因型频率与临床病理学参数及胃癌患者手术后生存时间无显著相关性,提示TJP1 rs 7179270 位点多态性可能不参与胃癌的进展和预后;TJP1 rs 34771010、rs 28578444和rs 41280058稀有等位基因频率为0.0,推测中国福建地区人群可能无这三个位点的多态性分布。      

雌激素受体基因ESR1多态性与乳腺癌易感性的关系

目的：研究雌激素受体α（ESR1）基因单核苷酸多态性（SNPs）与乳腺癌易感性的关系。方法：运用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析的方法检测193例中国汉族女性乳腺癌患者和71名正常女性对照者ESR1基因上rs11155816位点的基因型,以SPSS 11.0软件卡方检验处理数据。结果：rs11155816位点等位基因频率符合Hardy-Weinberg遗传平衡定律。rs11155816位点的等位基因及基因型与患者肿瘤位置及是否存在远处转移相关,差异有显著性（P〈0.05）;与年龄、大小、组织学类型、受体表达无关。rs11155816位点等位基因及基因型频率在乳腺癌人群与正常对照者间分布差异有显著性,乳腺癌人群中等位基因A频率高于正常人群（23.8%比15.5%,P〈0.05）。结论：rs11155816位点基因的多态性与乳腺癌患者的肿瘤位置和远处转移相关,等位基因A携带者乳腺癌发病风险较高。     

江西汉族女性BRCA2基因单核苷酸多态性与散发性乳腺癌易感相关性研究

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SequenomMassArrayiPLEX 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。     

ATM基因rs175048 位点单核苷酸多态性与湖南衡阳地区汉族人群肺癌易感性的相关性

[摘要] 目的: 探讨肺癌易感性与毛细血管扩张性共济失调突变基因(ATM) rs175048 位点单核苷酸多态性(SNP)之间的相关性。方法: 选取2015 年10 月至2016 年8 月在南华大学附属第一医院及衡阳市中医院就诊的汉族肺癌患者血液样本225 例(病例组),同时收集在院体检的健康人血液样本128 例作为对照组。采用高保真聚合酶介导的单核苷酸多态性敏感性分子开关结合PCR技术检测肺癌患者与健康体检者ATM基因rs175048A/T多态位点的多态性,统计其基因型及等位基因频率,比较其在病例组与对照组的分布差异,并且分析其与肺癌临床病理特征的相关性。结果:ATM基因rs175048 多态位点的AA、AT、TT 3 种基因型的频率在病例组分别为24.9%、52.9%、22.2%,对照组为42.2%、42.2%、15.6%（均P<0.01）;病例组等位基因A、T 的频率为51.0%、49.0%,对照组为63.0%、37.0%（均P<0.01）;TT基因型可能会增加、而AT基因型可能减少肺癌发病风险。rs175048 单核苷酸多态位点与吸烟、年龄、性别和家族史等临床病理特征明显相关(均P<0.05)。结论:ATM基因rs175048 位点单核苷酸多态性与肺癌的发生明显相关,且TT基因型可以增加肺癌发病的风险。     

Risk of aggressive breast cancer in women of Han nationality carrying TGFB1 rs1982073 C allele and FGFR2 rs1219648 G allele in North China

The high morbidity and aggressive behavior of breast cancer are associated with genetic variations. Single nucleotide polymorphisms (SNPs) in many genes have been demonstrated as a risk factor for breast cancer. In this study, we evaluated the association of the SNP rs1982073 (Leu10Pro) in transforming growth factor-beta 1 (TGFB1) gene and the SNP rs1219648 in fibroblast growth factor receptor 2 (FGFR2) gene with the risk and aggressiveness of breast cancer among women of Han nationality in North China. TaqMan allelic discrimination assay was performed to genotype rs1982073 and rs1219648 in 447 breast cancer cases and 406 age-matched healthy controls. The results imply that genotype frequencies of rs1982073 and rs1219648 were not significantly different between breast cancer patients and healthy controls. However, for TGFB1 SNP rs1982073, the C-carriers (T/C+C/C genotype) were more likely to bear tumors of greater aggressiveness (histological grade III) than T/T-carriers (grade I–II) (OR = 3.45, 95% CI: 1.48–8.00, P = 0.004). For FGFR2 SNP rs1219648, G-carriers (A/G+G/G genotype) were more significantly linked to tumors with lymph node metastasis than those with A/A genotype (lymph node negative) (OR = 1.69, 95% CI: 1.11–2.58, P = 0.016). Therefore, the SNPs of TGFB1 rs1982073 and FGFR2 rs1219648 may contribute to the identification of patients with more aggressive breast cancers among Han women in North China.     

Quantitative assessment of the effect of FGFR2 gene polymorphism on the risk of breast cancer

Fibroblast growth factor receptor 2 is a tyrosine kinase receptor that is a member of the family of individually distinct fibroblast growth factor receptors involved in cell proliferation, invasiveness, motility, and angiogenesis. Genome-wide association studies have identified FGFR2 as a breast cancer (BC) susceptibility gene in populations of European and Asian descent. After that, a number of studies reported that the rs2981582, rs1219648, and rs2420946 polymorphism in FGFR2 has been implicated in BC risk. However, studies on the association between these polymorphism and BC remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 46,747 cases and 87,342 controls from 16 published case–control studies was performed. Overall, significantly elevated BC risk was associated with rs2981582, rs1219648, and rs2420946 risk allele when all studies were pooled into the meta-analysis. Significant results were also observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the subgroup analysis by ethnicity, source of controls, significantly increased risks were found for these polymorphisms in all genetic model. In conclusion, this meta-analysis suggests that rs2981582, rs1219648, and rs2420946 polymorphisms in FGFR2 are associated with elevated BC risk.     

Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs: susceptibility and prognostic implications in Tunisians

Genome-wide Association Studies (GWAS) revealed novel genetic markers for breast cancer susceptibility. But little is known about the risk factors and molecular events associated with breast cancer in Arab Population. Therefore, we designed a broad study to investigate the susceptibility and prognostic implications of the GWAS breast cancer loci in the Tunisian population. In a cohort of 640 unrelated patients with breast cancer and 371 healthy control subjects, we characterized the variation of 9 single nucleotide polymorphisms (SNPs), namely rs1219648, rs2981582; rs8051542, rs12443621, and rs3803662; rs889312; rs3817198; rs13387042 and rs13281615. Only 5 out of 9 GWAS breast cancer loci were found to be significantly associated with breast cancer in Tunisians: The rs1219648 (G vs. A allele: OR?=?1.36, P?=?1?×?10(-3)) and rs2981582 (A vs. G allele: OR?=?1.55, P?=?3?×?10(-6)) of FGFR2 gene; the rs8051542 of the TNRC9 gene (T vs. C allele: OR?=?1.40, P?=?4?×?10(-4)); the rs889312 of the MAP3K1 gene (C vs. A allele: OR?=?1.33, P?=?3?×?10(-3)) and the rs13281615 located on 8q24 (G vs. A allele: OR?=?1.21, P?=?0.03). Homozygous variant genotypes of rs2981582 were strongly related to lymph node negative breast cancer (OR?=?3.33, P?=?6?×?10(-7)) and the minor allele of rs2981582 was associated with increased risk of ER+ tumors (OR?=?1.57, P?=?0.02; OR?=?2.15, P?=?0.001, for heterozygous and homozygous variant genotypes, respectively) and increased risk of distant metastasis development (OR?=?2.30, P?=?4?×?10(-3); OR?=?3.57, P?=?6?×?10(-5), for heterozygous and homozygous variant genotypes, respectively) in a dose dependent manner. The association for rs8051542 was stronger for high-grade SBR tumors (OR?=?2.54, P?=?2?×?10(-4)). GG genotype of rs13387042 on 2q35 showed a significant association with the risk of developing distant metastasis (OR?=?1.94, P?=?0.02). The G allele of rs1219648 in FGFR2 and the A allele of rs13387042 on 2q35 indicated a better prognosis by showing a significantly higher overall survival rates (P?=?0.013 and P?=?0.005, respectively). In conclusion, GWAS breast cancer FGFR2, TNRC9, MAP3K1, and 8q24 loci are associated with an increased risk of breast cancer and genetic variation in FGFR2 gene may predict the aggressiveness of breast cancer in Tunisians.     

Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population

Breast cancer is the most common cancer among women in the world. In Iran, the incidence of breast canceris on the increase. We here studied the association of rs1219648 in FGFR2 and rs1042522 in TP53 and theirinteraction in development of early onset sporadic breast cancer in Iranian Azeri population to evaluate epistaticeffects on the risk of mammary neoplasia. We genotyped the two polymorphisms in 100 women with early onsetbreast cancer and 100 healthy women by PCR-RFLP. Allele frequency differences were tested using chi2-test with95% confident intervals. Our results indicated a statistically significant association (p<0.05) between rs1219648,but not rs1042522, and risk of breast cancer. We also found that the combination of FGFR2 major genotypeand TP53 hetero genotype had protective effects against breast cancer , while the hetero allele of FGFR2 incombination with the minor genotype of TP53 was associated with a high risk. This study revealed an importantcrosstalk between two polymorphisms in FGFR2 and TP53 in development of breast cancer. These candidatesrisk variants should be further evaluated in studies with a larger sample size.     

Case-Control Study on the Fibroblast Growth Factor Receptor 2 Gene Polymorphisms Associated with Breast Cancer in Chinese Han Women

Purpose

Genetic variation in fibroblast growth factor receptor 2 (FGFR2) is a newly described risk factor for breast cancer. This study aimed to evaluate the association of four single nucleotide polymorphisms (SNPs) in FGFR2 with breast cancer in Han Chinese women.

Methods

Two hundred three women with breast cancer and 200 breast cancer-free age-matched controls were selected. Four SNPs (rs2981579, rs1219648, rs2420946, and rs2981582) and their haplotypes were analyzed to test for their association with breast cancer susceptibility. The presence of the four FGFR2 SNPs was determined by polymerase chain reaction-restriction fragment length polymorphism analysis.

Results

A statistically significant difference was observed in the frequency of rs2981582 in the FGFR2 gene (p<0.05) between case and control groups. In subjects stratified by menopausal status, rs2981582 TT, rs2420946 AA, and rs1219648 CC were significantly associated with the risk of breast cancer in postmenopausal subjects, but no significant associations between these four SNPs and the risk of breast cancer were identified in premenopausal subjects. Further, there was no significant association between hormone receptor status (estrogen receptor and progesterone receptor) and breast cancer risk. Six common (> 3%) haplotypes were identified. Three of these haplotypes, CGTC (odds ratio [OR], 0.613; 95% confidence interval [CI], 0.457-0.82; p=0.001), TGTC (OR, 6.561; 95% CI, 2.064-20.854; p<0.001), and CATC (OR, 12.645; 95% CI, 1.742-91.799; p=0.001) were significantly associated with breast cancer risk.

Conclusion

Our findings indicated that the SNP rs2981582 and haplotypes CGTC, TGTC, and CATC in FGFR2 may be associated with an increased risk of breast cancer in Han Chinese women.     

Breast cancer susceptibility alleles and ovarian cancer risk in 2 study populations

Recent genome-wide scans identified several novel breast cancer risk alleles, including variants of the FGFR2, MAP3K1 and LSP1 genes, and a study of associations between these alleles and characteristics of breast cancer patients reported a borderline significant correlation between the number of FGFR2 minor alleles and family history of breast/ovarian cancer. Given these results and similarities in the etiology of breast and ovarian cancer, we examined the association between 7 novel breast cancer susceptibility alleles and epithelial ovarian cancer risk in 2 large study populations. Our analysis included 1,173 cases and 1,201 controls from a New England-based Case-Control study and 210 cases and 603 controls from the prospective Nurses' Health Study. We used logistic regression to estimate the odds ratio (OR) for individuals heterozygous or homozygous for the minor allele at each locus, compared to individuals with the wild-type genotype. We examined the associations separately in each population and, after testing for heterogeneity in the results, pooled the estimates using a random effects model. There was no clear association between these polymorphisms and ovarian cancer risk in either population. The pooled per allele OR for FGFR2 was 1.06 (95% confidence interval (CI)=0.95-1.18) for rs1219648 and 1.04 (95% CI=0.93-1.15) for rs2981582. We had more than 80% power to detect a log-additive OR of 1.16-1.18 per allele at the alpha=0.05 level in the pooled analysis. Our results do not provide strong support for an association between these breast cancer susceptibility alleles and epithelial ovarian cancer risk.     

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相关性

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。     

Polymorphisms in tissue inhibitors of metalloproteinases‐2 and ‐3 and breast cancer susceptibility and survival

Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases which are involved in normal cellular processes and also in cancer development and progression. The purpose of this study was to evaluate polymorphisms in the TIMP‐2 and TIMP‐3 genes for their associations with breast cancer susceptibility and survival. Using data from the Shanghai Breast Cancer Study, 19 SNPs for each gene were evaluated for associations with breast cancer risk among 1,062 cases and 1,069 controls; associations with disease‐free and overall survival were evaluated among the cases. For TIMP‐2, women with the rs7501477 TT genotype were 3 times more likely to be breast cancer cases than women with the CC genotype (OR: 2.9, 95% CI: 1.2–7.0). For TIMP‐3, women with the rs9609643 AA genotype were 60% less likely to be breast cancer cases than women with the GG genotype (OR: 0.4, 95% CI: 0.2–1.0), whereas women with the rs8136803 TT genotype were 5 times more likely to be cases than women with the GG genotype (OR: 5.1, 95% CI: 1.1–24.3). Further, breast cancer cases with rs8136803 TT were almost 4 times more likely to have decreased disease‐free survival (HR: 3.9, 95% CI: 1.4–10.6) and had a trend toward decreased overall survival (HR: 1.9, 95% CI: 0.6–6.1). An important study limitation was that these 3 SNPs (rs7501477, rs9609643, rs8136803) had low minor allele frequencies which resulted in small numbers of homozygote individuals. Genetic variation in the TIMP‐2 and TIMP‐3 genes may contribute to individual differences in breast cancer susceptibility and survival. © 2009 UICC