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.     

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关联的研究

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。     

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。     

FGFR4基因多态性与 Luminal 型乳腺癌临床病理特征的相关性

目的：探讨 FGFR4基因多态性与 Luminal 型乳腺癌临床病理指标的关系,为临床个体化治疗提供理论依据。方法：采用多重单碱基延伸（Snapshot）SNP 分型技术,检测415例 Luminal 型乳腺癌患者2个 FGFR4基因多态位点。分析这些多态位点与 Luminal 型乳腺癌临床病理特征的关系。结果：在415例 Luminal 型乳腺癌中,FGFR4基因 rs1966265多态频率分布：纯合野生 AA 型为23．4％、杂合 GA 型为53．7％、纯合突变 GG型为22．9％;rs351855多态频率分布：纯合野生 GG 型为28．2％、杂合 GA 型为53．7％、纯合突变 AA 型为18．1％。两个多态位点与 Luminal 型乳腺癌临床分期、肿瘤大小、组织学分级、淋巴结转移无相关性（P ＞0．05）。结论：FGFR4基因 rs1966265和 rs351855位点多态性与 Luminal 型乳腺癌的临床病理特征之间无明显关联。     

Sipa1-545(C/T)基因多态与乳腺癌发病风险及临床病理参数相关性研究

目的:研究Sipa1-545基因多态与中国女性乳腺癌临床病理特征及发病风险的关系.方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测570例原发性乳腺癌患者及541例对照组健康人群Sipa1-545基因多态,分析基因多态性与乳腺癌发病风险及临床病理特征的相关性.结果:在570例乳腺癌患者中,Sipal-545(C/T)基因多态三种基因型分布频率为野生型C/C49.1%(280/570)、杂合型C/T 41.6%(237/570)、突变型T/T 9.3%(53/570);在541例健康对照人群中Sipa1-545基因多态分布频率为:C/C型47.1%(255/541)、C/T型42.1%(228/541)、T/T型10.7%(58/541).Sipa1-545基因多态与中国女性乳腺癌的发病风险无显著相关性(校正年龄后OR=0.82,95%CI:0.52～1.28,P=0.37).且Sipa1-545基因多态与乳腺癌患者发病年龄、腋淋巴结转移状态、TNM分期、雌激素受体(estrogen receptor,ER)和孕激素受体(progestogen receptor,PR)状态等均无显著相关性.但Sipa1-545基因多态与C-erbB2蛋白表达呈显著相关,Sipa1-545 T/T纯合突变型患者C-erbB2蛋白阳性表达率显著高于C/T杂合型和C/C纯合野生型患者(50.0% vs 31.9% or28.6%,P=0.014).结论:Sipa1-545基因多态与中国女性乳腺癌的发病风险无关,但是携带Sipa1-545T/T者可能更具恶性行为.     

XRCC1基因单核苷酸多态性与食管癌易感性的关系

目的探讨X线修复交叉互补基因(X-ray cross complementing group1,XRCC1)单核苷酸多态性(single nucleotide polymorphism,SNPs)与食管癌易感性及临床病理的关系。方法应用Sequenom MassARRAY时间飞行质谱系统对200例食管癌及200例对照者XRCC1基因10个多态位点进行基因型分型。统计分析基因型频率和食管癌易感性的关系,统计基因多态与食管癌临床病理之间的关系。结果 XRCC1基因10个多态位点,rs25491位点、rs3213242位点没有多态性。条件Logistic回归分析显示,rs25487位点在显性模型中等位基因频率在病例组和对照组间差异有统计学意义(OR=1.558,95%CI=1.020-2.381,P=0.040);rs1799778位点在显性模型中等位基因频率在病例组和对照组间差异有统计学意义(OR=1.558,95%CI=1.019-2.381,P=0.041);rs2682585位点基因频率在病例组和对照组间差异有统计学意义(OR=14.313,95%CI=5.188-39.489,P=0.000);其余位点两组间差异无统计学意义。没有发现有意义的单体型。未发现基因多态与食管癌临床病理特征之间的关系。结论 XRCC1基因SNP位点rs2682585、rs25487和rs1799778与食管癌发病风险有显著相关性,很可能是决定食管癌个体遗传易感性的重要因素,以上3个SNP位点与食管癌临床病理特征之间无相关性。     

FGFR3基因单核苷酸多态与绝经前乳腺癌易感性的关联研究

目的 探讨FGFR3基因单核苷酸多态(SNPs)与女性绝经前乳腺癌的风险关系。方法 采用多重单碱基延伸SNP分型技术(Snapshot)检测FGFR3基因的rs2234909和rs3135848的SNP基因型在绝经前乳腺癌患者和绝经前正常女性人群中的频率,并分析不同SNP基因型与绝经前乳腺癌发病的风险关系。结果 FGFR3基因rs2234909和rs3135848的SNP基因型的频率在乳腺癌与对照组间无统计学差异(P＞0.05)。Logistic回归分析结果显示,对于rs2234909位点,相比较于TT基因型,TC和TC+CC基因型和乳腺癌的发病风险无显著相关性(OR=1.035,95% CI:0.680~1.575,P=0.874;OR=0.985,95% CI:0.638~1.521,P=0.945);对于rs3135848位点,相比较于TT基因型,TC、CC和TC+CC基因型与乳腺癌的发病风险无关(OR=1.177,95% CI:0.846~1.636,P=0.333;OR=0.948,95% CI:0.287~3.137,P=0.931;OR=1.162,95% CI:0.548~1.112,P=0.360)。rs2234909位点突变的乳腺癌患者与未突变者相比,组织学分级(显性模型:P=0.032;共显性模型:P=0.024)以及Ki67指数(显性模型:P=0.056;共显性模型:P=0.044)显著增高;rs3135848位点突变及两位点均突变与乳腺癌患者临床病理特征无显著相关性(P＞0.05)。结论 FGFR3基因的rs2234909和rs3135848两位点基因多态性与乳腺癌易感性无明显相关性;而rs2234909位点突变在绝经前乳腺癌患者中与组织学分级和Ki67指数呈正相关,可能提示预后不良。     

ErbB4基因micro-RNA靶序列单核苷酸多态性与乳腺癌易感性的关系

目的:探讨ErbB4基因micro-RNA靶序列单核苷酸多态性与乳腺癌易感性的关系。方法:采用TaqMan单核苷酸多态(single nucleotide polymorphism,SNP)分型技术检测1509例乳腺癌患者和1517例健康对照者外周血中ErbB4基因micro-RNA靶序列rs1595066及rs16845990位点的基因型。结果:ErbB4基因micro-RNA靶序列rs16845990位点3种基因型在乳腺癌患者和健康对照者间的分布差异无统计学意义(P=0.302);rs1595066位点3种基因型在2组间的分布差异有统计学意义(P=0.045),与GG型相比,杂合型AG及纯合型AA均可显著降低乳腺癌的发病风险,调整后比值比(oddsratios,OR)及其95%可信区间(confidenceintervals,CI)分别为0.81(0.69～0.95)和0.75(0.58～0.96)。分层分析显示,此保护作用在年龄≥55岁、无肿瘤家族史和无乳腺良性疾病史者中更显著。结论:ErbB4基因micro-RNA靶序列rs1595066G>A位点A等位基因可能降低乳腺癌的发病风险。     

乳腺癌中HER-2基因多态性与蛋白表达的相关性研究

背景与目的：致病基因的多态性可能会影响该基因的功能,从而引起个体肿瘤易感性的差异和个体内生物活性物质效应的改变。本研究旨在研究HER-2基因多态性与其蛋白表达的关系,并分析其与乳腺癌临床病理特征的相关性。方法：收集303例汉族女性乳腺癌患者为研究对象,运用MassARRAY技术平台检测HER-2基因rs2517954和rs2517955单核苷酸多态性。同时采用免疫组织化学法检测相应乳腺癌组织中HER-2蛋白表达并检测雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、P53及Ki67表达。以Pearson χ2分析这两个位点和其蛋白表达的关系,并分析其与乳腺癌临床病理特征的相关性。结果：在共显性模型下,HER-2基因rs2517954和rs2517955位点多态性与其蛋白表达相关(χ2=9.613,P=0.008;χ2=9.613,P=0.008)。在显性模型下,HER-2基因rs2517955位点TT纯合突变型和CT杂合突变型的频率与其蛋白表达相关(χ2=8.894,P=0.003)。HER-2基因rs2517954和rs2517955位点多态性与患者的临床分期、肿瘤大小、组织学分级、淋巴结转移、ER、PR、Ki67及P53表达均无显著相关性(P＞0.05)。结论：HER-2基因rs2517955多态性位点与其蛋白表达具有相关性,对该位点进一步研究可能有助于阐明乳腺癌中HER-2蛋白的表达机制。     

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。     

Genetic variants in trinucleotide repeat-containing 9 (TNRC9) are associated with risk of estrogen receptor positive breast cancer in a Chinese population

Trinucleotide repeat-containing 9 (TNRC9), a high mobility group chromatin-associated protein, has been implicated in breast cancer metastasis to the bone. Recently, several single nucleotide polymorphisms (SNPs) of TNRC9 were identified as novel breast cancer susceptibility loci by whole genome association studies, especially in estrogen receptor (ER) positive tumors. In the present case–control study of 1,049 breast cancer patients and 1,073 cancer-free controls in a Chinese population, we genotyped three polymorphisms (rs3803662C/T, rs12443621A/G, and rs8051542C/T) of the TNRC9 gene using the SNPstream 12-plex platform to test the hypothesis that these SNPs are associated with breast cancer risk in this population. None of the three polymorphisms was significantly associated with breast cancer risk in the whole data set (P = 0.151, 0.644, and 0.737 for rs3803662, rs12443621. and rs8051542, respectively). However, rs12443621 AG/GG genotypes were significantly associated with increased risk of ER positive breast cancer (OR = 1.38, 95% CI = 1.01–1.88), compared with homozygote AA. In addition, a borderline significantly increased risk was also observed for the variant genotypes (CT/TT) of rs8051542 C/T compared with the wild-type genotype (CC) (adjusted OR = 1.26, 95% CI = 0.99–1.60). Interestingly, a significant interaction was detected between rs12443621A/G and ER status on breast cancer risk in a case-only analysis (P for interaction = 0.004). These findings suggest that genetic variants of TNRC9 may contribute to the development of ER positive breast cancer.     

Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction

The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10(-11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.     

Association between single nucleotide polymorphisms on chromosome 17q and the risk of prostate cancer in a Chinese population

In European populations, 7 single nucleotide polymorphisms (SNPs) on chromosome 17q, 3 SNPs on 17q12, and 4 SNPs on 17q24.3 were recently identified to be closely related to the risk of prostate cancer by a genome-wide association study. In Japanese populations, the correlation between 2 SNPs on 17q and the risk of prostate cancer and tumor aggressiveness was also confirmed by a large-scale experiment. However, whether 17q is associated with prostate cancer and its clinical manifestations in Chinese populations is still unknown. Therefore, we conducted a case-control study in a northern Chinese population and tested 2 SNPs, rs4430796 and rs1859962, on 17q in 124 prostate cancer patients and 111 controls using polymerase chain reaction-high resolution melting curve (PCR-HRM) combined with sequencing. We analyzed the association of the 2 SNPs with the risk of prostate cancer as well as patients' lifestyles, onset ages, Gleason scores, PSA levels, and pathologic stages. We found a significant difference in the G allele of SNP rs1859962 (P = 0.035, OR = 1.51, 95% CI = 1.03-2.21) but not in the rs4430796 genotype frequency or allele frequency distribution between prostate cancer patients and the controls (P > 0.05). Neither of the SNPs was significantly associated with the onset age, Gleason score, PSA level, pathologic stage, or other clinical indicators of patients with prostate cancer (P > 0.05). Our results show that polymorphism of the G allele of SNP rs1859962 is associated with the risk of prostate cancer in a Chinese population.     

Vitamin D receptor variants and breast cancer risk in the Polish population

The aim of the study was to determine whether four VDR gene single nucleotide polymorphisms (SNPs: rs1544410, rs731236, rs10735810 and rs4516035) are associated with breast cancer risk in Polish population. Two independent series of female patients were employed: 960 consecutive breast cancer cases, and 800 unselected early onset cases diagnosed under the age of 51. The control group for the consecutive breast cancer cases consisted of 960 healthy, age-matched women with a negative cancer family history. 550 healthy women, aged 51 or less, with negative cancer family history were selected as the independent controls for the early onset breast cancer cases. The frequencies of the VDR polymorphisms in the unselected cases when compared to the respective control population failed to reveal any association between the individual SNPs and disease. Examination of the group of early-onset patients, revealed an association between rs10735810 and increased breast cancer risk. Heterozygous carriers for the change had an OR = 1.73 (95% CI 1.33–2.26, P < 0.0001) and homozygous carriers OR = 2.34 (95% CI 1.71–3.21, P < 0.0001). The remaining three examined SNPs failed to show any association with disease risk. In summary, this study has identified an association between the VDR gene and early onset breast cancer risk in the Polish population.     

Breast cancer susceptibility loci and mammographic density

Introduction

Recently, the Breast Cancer Association Consortium (BCAC) conducted a multi-stage genome-wide association study and identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Given the high degree of heritability of mammographic density and its strong association with breast cancer, it was hypothesised that breast cancer susceptibility loci may also be associated with breast density and provide insight into the biology of breast density and how it influences breast cancer risk.

Methods

We conducted an analysis in the Nurses' Health Study (n = 1121) to assess the relation between 11 breast cancer susceptibility loci and mammographic density. At the time of their mammogram, 217 women were premenopausal and 904 women were postmenopausal. We used generalised linear models adjusted for covariates to determine the mean percentage of breast density according to genotype.

Results

Overall, no association between the 11 breast cancer susceptibility loci and mammographic density was seen. Among the premenopausal women, three SNPs (rs12443621 [TNRc9/LOC643714], rs3817198 [lymphocyte-specific protein-1] and rs4666451) were marginally associated with mammographic density (p < 0.10). All three of these SNPs showed an association that was consistent with the direction in which these alleles influence breast cancer risk. The difference in mean percentage mammographic density comparing homozygous wildtypes to homozygous variants ranged from 6.3 to 8.0%. None of the 11 breast cancer loci were associated with postmenopausal breast density.

Conclusion

Overall, breast cancer susceptibility loci identified through a genome-wide association study do not appear to be associated with breast cancer risk.     

Genotypes and phenotypes of IGF-I and IGFBP-3 in breast tumors among Chinese women

The relationship between IGF genotypes and phenotypes in breast tumors and their associations with breast cancer risk remain to be elucidated. Such information is especially scarce in Chinese women. To evaluate IGF-I and IGFBP-3 genotypes in relation to their phenotypes in local breast tissues and in association with breast cancer risk, we conducted a case–control study among Chinese women. The study recruited 403 breast cancer patients and 403 age-matched controls. Four single nucleotide polymorphisms (SNP) in the IGF-I gene (rs1520220, rs2946834, rs2195239, and rs7965399) and two SNPs of the IGFBP-3 gene (rs2854746 and rs2960436) with known correlations with their phenotypes in the circulation were genotyped using TaqMan assays. Fresh tumor samples from the same patients were analyzed with immunoassays for protein concentrations of IGF-I and IGFBP-3. Associations of breast cancer with these SNPs were examined using unconditional logistic regression. Correlations between IGF genotypes and phenotypes were determined with Wilcoxon rank-sum test. Of the six selected SNPs, only one IGF-I SNP (rs7965399) was associated with breast cancer risk in a recessive model (OR = 1.86; 95% CI: 1.04–3.32), and the association was more evident in patients who had menopause under age 50 or ER negative tumors. No associations were found between breast cancer and other three IGF-I and two IGFBP-3 SNPs. Patients with variant IGF-I or wild IGFBP-3 genotypes had higher peptide levels of IGF-I compared to those with wild IGF-I or variant IGFBP-3 genotypes. The selected IGF-I and IGFBP-3 SNPs did not show any strong evidence for being associated with breast cancer risk, but the genotypes were correlated with IGF-I phenotypes in tumor samples, suggesting possible influences of these SNPs on IGF-I activity in local tissues.     

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.