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Association of OX40L Polymorphisms with Sporadic Breast Cancer in Northeast Chinese Han Population  [PDF]
Yuan Weiguang, Li Dalin, Xu Lidan, Cai Yonggang, Chen Shuang, Liu Yanhong, Xu Fengyan, Fu Zhenkun, Pang Da, Li Dianjun
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0041277
Abstract: OX40L is an important costimulatory molecule that plays a crucial role in the regulation of T-cell-mediated immunity. The interaction of OX40-OX40L is involved in the pathogenesis of multiple autoimmune and inflammatory diseases such as systemic lupus erythematosus (SLE), carotid artery disease and cancer. The genetic variants of OX40L can increase the risk of SLE, atherosclerosis, systemic sclerosis and show gender-specific effects in some studies. Accordingly, we performed a case-control study including 557 breast cancer patients and 580 age- and sex-matched healthy controls to investigate whether single nucleotide polymorphisms (SNPs) in the OX40L gene are associated with sporadic breast cancer susceptibility and progression in Chinese Han women. Seven SNPs of OX40L (rs6661173, rs1234313, rs3850641, rs1234315, rs12039904, rs844648 and rs10912580) were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results indicated that rs3850641G allele could increase the susceptibility to breast cancer (P = 0.009662), even in the validation study (P = 0.0001515). A significant association between rs3850641 and breast cancer risk was observed under the additive model and dominant model (P = 0.01042 and 0.01942, respectively). The haplotype analysis showed that haplotype Ars844648Ars10912580 was significantly associated with breast cancer, even after 10,000 permutations for haplotypes in block only (P = 0.0003). In clinicopathologic features analysis, the association between rs1234315 and C-erbB2 status was significant (P = 0.02541). Our data primarily indicates that rs3850641 of OX40L gene contributes to sporadic breast carcinogenesis in a northeast Chinese Han population.
Association of CD40 Gene Polymorphisms with Sporadic Breast Cancer in Chinese Han Women of Northeast China  [PDF]
Chen Shuang, Li Dalin, Yuan Weiguang, Fu Zhenkun, Xu Fengyan, Pang Da, Dianjun Li
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023762
Abstract: Background Breast cancer is a polygenetic disorder with a complex inheritance pattern. Single nucleotide polymorphisms (SNPs), the most common genetic variations, influence not only phenotypic traits, but also interindividual predisposition to disease, treatment outcomes with drugs and disease prognosis. The co-stimulatory molecule CD40 plays a prominent role in immune regulation and homeostasis. Accumulating evidence suggests that CD40 contributes to the pathogenesis of cancer. Here, we set out to test the association between polymorphisms in the CD40 gene and breast carcinogenesis and tumor pathology. Methodology and Principal Findings Four SNPs (rs1800686, rs1883832, rs4810485 and rs3765459) were genotyped by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method in a case-control study including 591 breast cancer patients and 600 age-matched healthy controls. Differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed by the Chi-square test for trends. Our preliminary data showed a statistically significant association between the four CD40 gene SNPs and sporadic breast cancer risk (additive P = 0.0223, 0.0012, 0.0013 and 0.0279, respectively). A strong association was also found using the dominant, recessive and homozygote comparison genetic models. In the clinical features analysis, significant associations were observed between CD40 SNPs and lymph node metastasis, human epidermal growth factor receptor 2 (C-erbB2), estrogen receptor (ER), progesterone receptor (PR) and tumor protein 53 (P53) statuses. In addition, our haplotype analysis indicated that the haplotype Crs1883832Grs4810485, which was located within the only linkage disequilibrium (LD) block identified, was a protective haplotype for breast cancer, whereas Trs1883832Trs4810485 increased the risk in the studied population, even after correcting the P value for multiple testing (P = 0.0337 and 0.0430, respectively). Conclusions and Significance Our findings primarily show that CD40 gene polymorphisms contribute to sporadic breast cancer risk and have a significant association with clinicopathological features among Chinese Han women from the Heilongjiang Province.
Association of TNF-α, TNFRSF1A and TNFRSF1B Gene Polymorphisms with the Risk of Sporadic Breast Cancer in Northeast Chinese Han Women  [PDF]
Fengyan Xu, Guiqin Zhou, Shaoli Han, Weiguang Yuan, Shuang Chen, Zhenkun Fu, Dalin Li, Hua Zhang, Dianjun Li, Da Pang
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0101138
Abstract: Background The interaction of tumor necrosis factor-α (TNF-α) with its receptors: TNFRSF1A and TNFRSF1B is critical for the promotion of tumor growth, invasion and metastasis. To better understand the roles of single nucleotide polymorphisms (SNPs) in the TNF-α, TNFRSF1A and TNFRSF1B genes in the development of breast cancer, we explored the associations between SNPs in these three genes and breast cancer susceptibility in northeast Chinese Han women. Methodology/Principal Findings This case-control study was conducted among 1016 breast cancer patients and 806 age-matched healthy controls. Seven SNPs in the TNF-α (rs1800629, rs361525), TNFRSF1A (rs767455, rs4149577 and rs1800693) and TNFRSF1B (rs1061622 and rs1061624) genes were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In TNFRSF1B, the rs1061622 GT genotype and the G allele conferred a reduced susceptibility to breast cancer (P = 0.000662, OR = 0.706, 95% CI: 0.578–0.863; P = 0.002, OR = 0.769, 95% CI; 0.654–0.905, respectively). Moreover, the AG genotype, the AA genotype and the A allele in rs1061624 conferred an increased risk of breast cancer (P = 0.007, OR = 1.470, 95% CI:1.112–1.943; P = 0.00109, OR = 1.405 95% CI:1.145–1.724; P = 0.001, OR = 1.248 95% CI:1.092–1.426, respectively). These two SNPs also had associations with breast cancer risk under the dominant model. In haplotype analysis, the CTA (rs767455 C-rs4149577 T-rs1800693 A) haplotype in TNFRSF1A and the TA (rs1061622 T-rs1061624 A) haplotype in TNFRSF1B had higher frequencies in breast cancer patients (P = 0.00324; P = 0.000370, respectively), but the frequency of GG (rs1061622 G-rs1061624 G) haplotype in TNFRSF1B was lower in breast cancer patients (P = 0.000251). The associations of the three haplotypes remained significant after correcting for multiple testing. In addition, significant associations were also observed between TNFRSF1A polymorphisms and lymph node metastasis, P53, estrogen receptor (ER) and progesterone receptor (PR) statuses. Conclusions Our results suggest that rs1061622 and rs1061624 in TNFRSF1B may affect breast cancer risk, and SNPs in TNFRSF1A are associated with the clinical features of breast cancer.
HVEM Gene Polymorphisms Are Associated with Sporadic Breast Cancer in Chinese Women  [PDF]
Dalin Li, Zhenkun Fu, Shuang Chen, Weiguang Yuan, Yanhong Liu, Liqun Li, Da Pang, Dianjun Li
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0071040
Abstract: As a costimulatory molecule, Herpesvirus entry mediator (HVEM) can bind with several costimulatory members, thus HVEM plays different roles in T cell immunity. HVEM and its ligands have been involved in the pathogenesis of various autoimmune, inflammatory diseases and tumors. In the current study, we conducted a case-control study comparing polymorphisms of HVEM and breast cancer. Subjects included 575 females with breast cancer and 604 age-matched healthy controls. Six HVEM SNPs (rs2281852, rs1886730, rs2234163, rs11573979, rs2234165, and rs2234167) were genotyped by PCR-RFLP. The results showed significant differences in genotypes and alleles between rs1886730 and rs2234167 (P<0.05). One haplotype (CTGCGG) that was associated with breast cancer was found via haplotype analysis. Our research also indicated an association between polymorphisms of HVEM and clinicopathologic features, including lymph node metastasis, estrogen receptor, progesterone receptor and P53. Our results primarily indicate that polymorphisms of the HVEM gene were associated with the risk of sporadic breast cancer in northeast Chinese females.
B7-H4 gene polymorphisms are associated with sporadic breast cancer in a Chinese Han population
Jie Zhang, Mingyan Zhang, Wei Jiang, Lihong Wang, Zhenkun Fu, Dalin Li, Da Pang, Dianjun Li
BMC Cancer , 2009, DOI: 10.1186/1471-2407-9-394
Abstract: We genotyped three B7-H4 variants (rs10754339, rs10801935 and rs3738414) and tagged all common haplotypes (frequency greater than or equal to 1%) in a Chinese population consisting of 500 breast cancer cases and 504 control individuals matched for age. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to determine the genotypes.Our data indicated that, compared with the common genotype and allele of each SNP, the rs10754339 AG genotype and G allele showed a significantly increased risk of breast cancer (OR = 1.455, 95% CI 1.119-1.892; OR = 1.325, 95% CI 1.073-1.637, respectively). The rs10801935 CC genotype, the rs3738414 AA genotype and the rs3738414 A allele were associated with a significantly decreased risk of breast cancer (OR = 0.328, 95% CI 0.145-0.739; OR = 0.412, 95% CI 0.203-0.835; OR = 0.698, 95% CI 0.564-0.864, respectively). Additionally, the rs10754339 GG genotype was significantly associated with lymph node metastasis and PR status, and the G allele and the AG genotype were respectively associated with lymph node metastasis and ER status. In haplotype analysis, we observed that compared with the AAG haplotype, the AAA haplotype showed a significantly decreased risk of breast cancer (OR = 0.689, 95% CI 0.539-0.881), but the GAG haplotype was associated with a significantly increased risk of breast cancer (OR = 1.511, 95% CI 1.125-2.031). And the AAA and the GCG haplotypes also respectively have significant influences on tumor size and ER status.These results suggest that B7-H4 gene polymorphism may contribute to the sporadic breast cancer risk and prognosis in Chinese Han women.Breast cancer is one of the most common malignant tumors in females, and its etiology as well as prognosis is extremely complex. The immune system, which plays an important role of immune surveillance in finding and eliminating cancer cells, can influence the development and growth of breast cancer. The central regulator of anti-tum
Association of CTLA-4 gene polymorphisms with sporadic breast cancer in Chinese Han population
Lihong Wang, Dalin Li, Zhenkun Fu, Heng Li, Wei Jiang, Dianjun Li
BMC Cancer , 2007, DOI: 10.1186/1471-2407-7-173
Abstract: We genotyped CTLA-4 variants (-1661 G/A, -658 T/C, -318 T/C, +49 G/A and CT60 G/A) to tag all common haplotypes (≥ 1% frequency) in 117 Chinese breast cancer cases and 148 age/sex matched healthy individuals. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data was analyzed using the Chi-square test and Haploview software.The frequency of CTLA-4 -1661G allele, -318T allele and CT60G allele carriers was significantly higher in patients than in controls (P = 0.0057, OR 1.91, 95% CI 1.21–3.02; P = 0.0031, OR 2.39, 95% CI 1.34–4.27; P = 0.023, OR 1.52, 95% CI 1.06–2.17, respectively). The -658T allele carrier frequency was significantly lower than in controls (P = 0.0000082, OR 0.17, 95% CI 0.08–0.37), whereas the +49A allele was significantly associated with tumor size in patients (P = 0.0033). Two common CTLA-4 haplotypes, ATCGA and ATCAG, were higher in healthy controls than patients (P = 0.0026, OR 0.17, 95% CI 0.05–0.54; P = 0.034, OR 0.12, 95% CI 0.02–0.92, respectively). A strong association was observed between tumor size and the ACCAA, ACCAG and ACCGA haplotypes (P = 0.0032, P = 0.0000031 and P = 0.017).These results suggest that polymorphisms of the CTLA-4 gene may modify individual susceptibility to and progression of breast cancer in Chinese Han women.Breast cancer is the most common malignancy in women worldwide and its rate is increasing in both developed and developing countries. The etiology of breast cancer is complicated and not completely known, but recent studies have focused on the role of the immune system. During the development of breast cancer, innate and adaptive responses are carefully orchestrated through soluble and membrane-bound regulators, resulting in the deployment of the most suitable effectors for controlling the growth of tumor. However, the biological importance of these responses is not fully understood [1]. The most significant anti-tumor response is cell-media
Thymidylate synthase gene (TYMS) polymorphisms in sporadic and hereditary breast cancer
José da Silva Nogueira Junior, Fernando Augusto de Lima Marson, Carmen Sílvia Bertuzzo
BMC Research Notes , 2012, DOI: 10.1186/1756-0500-5-676
Abstract: In this study we included a total of 204 subjects, 70 with BC (33 with SBC, and 37 with HBC) and 134 healthy subjects (controls). The Polymerase Chain Reaction was the method used.Results demonstrated a high frequency of the 3R allele at BC, SBC, and HBC groups. The frequency of genotype 2R/3R was significantly higher in BC group. This work showed association between the 2R/3R variants (OR = 4.14, CI95% = 1.77-9.71) in the development of SBC, and 2R/2R (OR = 0.233, CI95% = 1.63-7.65) and 2R/3R (OR = 3.53, CI95% = 0.06-0.81) for developing HBC. To BC, there was association with the genotype 2R/3R (OR: 3.79, CI95% = 2.03-7.08).Our results show relation to the development of BC in association with the analyzed polymorphisms.Breast cancer (BC) is a genetic disease characterized by an out of control growing breast cells, resulting in cellular proliferation, invasion of surrounding tissues and other organs, with possibility of metastasis [1]. BC is the second leading cancer in the population, it is the most common cancer among women, and the second leading cause of death within them, with approximately 460.000 deaths/year worldwide [1,2].In recent years risk factors for BC have been identified, although the etiology of the disease is still not understood. Risk factors that contribute to the development of BC include age, ethnicity, reproduction, some kind of hormones, lifestyle, bone density, genetic factors [3] and family history [4]. The majority of hereditary breast cancer (HBC) susceptibility can be attributed to germline mutations of to Breast Cancer 1 and Breast Cancer 2 genes (BRCA1 and BRCA2), which are responsible for 30-40% of HBC. Clinically, the basis of HBC is established at an early age, family history, bilateral BC, male BC, ovarian and/or tube cancer, and lower survival when compared to the sporadic form [5].Most of BC are sporadic (SBC), resulting from gene mutations, uncorrected, located in somatic cells, and unrelated to germline mutation. Risk factors
Association Analysis of IL-17A and IL-17F Polymorphisms in Chinese Han Women with Breast Cancer  [PDF]
Lihong Wang, Yongdong Jiang, Youxue Zhang, Yuwen Wang, Sunhui Huang, Zhihua Wang, Baoling Tian, Yue Yang, Wei Jiang, Da Pang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034400
Abstract: Background Research into the etiology of breast cancer has recently focused on the role of the immunity and inflammation. The proinflammatory cytokines IL-17A and IL-17F can mediate inflammation and cancer. To evaluate the influences of IL-17A and IL-17F gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in Chinese Han women. Methodology and Principal Findings We genotyped three single-nucleotide polymorphisms (SNPs) in IL-17A (rs2275913, rs3819025 and rs3748067) and five SNPs in IL-17F (rs7771511, rs9382084, rs12203582, rs1266828 and rs763780) to determine the haplotypes in 491 women with breast cancer and 502 healthy individuals. The genotypes were determined using the SNaPshot technique. The differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed with the Chi-square test for trends. For rs2275913 in IL-17A, the frequency of the AA genotype was higher in patients than controls (P = 0.0016). The clinical features analysis demonstrated significant associations between IL-17 SNPs and tumor protein 53 (P53), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and triple-negative (ER-/PR-/Her-2-) status. In addition, the haplotype analysis indicated that the frequency of the haplotype Ars2275913Grs3819025Grs3748067, located in the IL-17A linkage disequilibrium (LD) block, was higher in patients than in controls (P = 0.0471 after correction for multiple testing). Conclusions and Significance Our results suggested that SNPs in IL-17A but not IL-17F were associated with the risk of breast cancer. Both IL-17A and IL-17F gene polymorphisms may provide valuable information for predicting the prognosis of breast cancer in Chinese women.
Mitochondrial Haplogroups and Polymorphisms Reveal No Association with Sporadic Prostate Cancer in a Southern European Population  [PDF]
María Jesús álvarez-Cubero, María Saiz Guinaldo, Luís Javier Martínez-González, Juan Carlos álvarez Merino, José Manuel Cózar Olmo, José Antonio Lorente Acosta
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0041201
Abstract: Background It is known that mitochondria play an important role in certain cancers (prostate, renal, breast, or colorectal) and coronary disease. These organelles play an essential role in apoptosis and the production of reactive oxygen species; in addition, mtDNA also reveals the history of populations and ancient human migration. All these events and variations in the mitochondrial genome are thought to cause some cancers, including prostate cancer, and also help us to group individuals into common origin groups. The aim of the present study is to analyze the different haplogroups and variations in the sequence in the mitochondrial genome of a southern European population consisting of subjects affected (n = 239) and non-affected (n = 150) by sporadic prostate cancer. Methodology and Principal Findings Using primer extension analysis and DNA sequencing, we identified the nine major European haplogroups and CR polymorphisms. The frequencies of the haplogroups did not differ between patients and control cohorts, whereas the CR polymorphism T16356C was significantly higher in patients with PC compared to the controls (p = 0.029). PSA, staging, and Gleason score were associated with none of the nine major European haplogroups. The CR polymorphisms G16129A (p = 0.007) and T16224C (p = 0.022) were significantly associated with Gleason score, whereas T16311C (p = 0.046) was linked with T-stage. Conclusions and Significance Our results do not suggest that mtDNA haplogroups could be involved in sporadic prostate cancer etiology and pathogenesis as previous studies performed in middle Europe population. Although some significant associations have been obtained in studying CR polymorphisms, further studies should be performed to validate these results.
HLA-DRB1 Alleles Are Associated with the Susceptibility to Sporadic Parkinson’s Disease in Chinese Han Population  [PDF]
Congcong Sun, Lei Wei, Feifei Luo, Yi Li, Jiaobiao Li, Feiqi Zhu, Ping Kang, Rensi Xu, LuLu Xiao, Zhuolin Liu, Pingyi Xu
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048594
Abstract: Immune disorders may play an important role in the pathogenesis of Parkinson's disease (PD). Recently, polymorphisms in the HLA-DR region have been found to be associated with sporadic PD in European ancestry populations. However, polymorphisms in the HLA complex are highly variable with ethnic and geographic origin. To explore the relationships between polymorphisms of the HLA-DR region and sporadic PD in Chinese Han population, we genotyped 567 sporadic PD patients and 746 healthy controls in two independent series for the HLA-DRB1 locus with Polymerase chain reaction-sequence based typing(PCR-SBT). The χ2 test was used to evaluate the distribution of allele frequencies between the patients and healthy controls. The impact of HLA-DRB1 alleles on PD risk was estimated by unconditional logistic regression. We found a significant higher frequency of HLA-DRB1*0301 in sporadic PD patients than in healthy controls and a positive association, which was independent of onset age, between HLA-DRB1*0301 and PD risk. Conversely, a lower frequency of HLA-DRB1*0406 was found in sporadic PD patients than in healthy controls, with a negative association between HLA-DRB1*0406 and PD risk. Furthermore, a meta-analysis involving 195205 individuals was conducted to summarize the frequencies of these two alleles in populations from various ethnic regions, we found a higher frequency of HLA-DRB1*0301, but a lower frequency of HLA-DRB1*0406 in European ancestry populations than that in Asians, this was consistent with the higher prevalence of sporadic PD in European ancestry populations. Based on these results, we speculate that HLA-DRB1 alleles are associated with the susceptibility to sporadic PD in Chinese Han population, among them HLA-DRB1*0301 is a risk allele while the effect of HLA-DRB1*0406 deserves debate.
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