Association of genetic polymorphisms in the interleukin-10 promoter with risk of prostate cancer in Chinese

Background  

Recent studies identified an increased risk of prostate cancer (PCa) in Caucasian men harboring polymorphisms of genes involved in innate immunity and inflammation. This study was designed to assess whether single nucleotide polymorphisms in the IL-10 promoter play a role in predisposing individuals to PCa in a Chinese population.     

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。     

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。     

Association of interleukin-10 gene polymorphisms with breast cancer in a Chinese population

Backgroud

Interleukin-10(IL-10) is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population.

Methods

We genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP).

Results

There were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN) involvement (P = 0.041) and larger tumor size (P = 0.039) at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p = 0.022) and higher tumor stage(p = 0.028) of breast cancer at the time of diagnosis compared with others.

Conclusions

Our findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.     

The association between two polymorphisms in pre-miRNAs and breast cancer risk: a meta-analysis

Emerging evidence has shown that miRNAs participate in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphism (SNP) which located in the pre-miRNA may affect the processing and then influence the expression of mature miRNA. Previous studies yielded conflicting results as to the association of two common polymorphisms in pre-miRNAs (i.e. hsa-miR-146 rs2910164 and hsa-miR-196a2 rs11614913) with breast cancer. To derive a more precise effect on the association between these polymorphisms and breast cancer risk, we conducted a meta-analysis. Through retrieving PubMed for the period up to May 2010, a total of four studies were identified with 3,007 cases and 3,718 controls for has-miR-146a rs2910164 polymorphism and with 3,287 cases and 4,298 controls for hsa-miR-196a2 rs11614913 polymorphism. We found that individuals carrying CC genotype of has-miR-196a2 rs11614913 polymorphism was associated with an increased breast cancer risk in homozygote comparison (OR = 1.30; 95% CI, 1.01-1.68), and dominant model (OR = 1.11; 95% CI, 1.01-1.23). However, no significant association between has-miR-146a rs2910164 polymorphism and breast cancer risk was observed in all comparison models tested. These findings suggest that has-miR-196a2 rs11614913 polymorphism may play crucial roles in breast cancer development.     

The association between two polymorphisms of eNOS and breast cancer risk: a meta-analysis

Breast cancer is one of the most common malignant tumors worldwide. Endothelial nitric oxide synthase (eNOS) plays a key role in breast cancer development. The associations between the two eNOS polymorphisms (E298D rs1799983, −786T>C rs2070744) and breast cancer risk are inconclusive. A meta-analysis was performed in this study. By searching Medline, ISI Web of Knowledge, ScienceDirect, EBSCO, CNKI, and SinoMed database, six case–control studies were collected for the eNOS E298D polymorphism (3,038 cases and 2,508 controls) and three case–control studies were eligible for the eNOS −786T>C polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between the two eNOS polymorphisms and breast cancer risk. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Overall, significantly decreased risk was observed for E298D (for EE vs. DD: OR = 0.74, 95% CI = 0.59–0.94; for ED vs. DD: OR = 0.78, 95% CI = 0.61–0.98; for dominant model: OR = 0.77, 95% CI = 0.61–0.96) and −786T > C (for TT vs. CC: OR = 0.60, 95% CI = 0.42–0.86; for dominant model: OR = 0.66, 95% CI = 0.47–0.94). In the subgroup analysis by ethnicity, significant decreased risks were found for E298D (for EE vs. DD: OR = 0.75, 95% CI = 0.56–0.99) and −786T>C (for TT vs. CC: OR = 0.53, 95% CI = 0.35–0.81; for dominant model: OR = 0.61, 95% CI = 0.41–0.91; for recessive model: OR = 0.70, 95% CI = 0.55–0.91) among Caucasians; significant decreased risks were observed for E298D (for ED vs. DD: OR = 0.12, 95% CI = 0.02–0.96; for dominant model: OR = 0.13, 95% CI = 0.02–1.00) among Asians. In conclusion, this meta-analysis suggests that both eNOS E298D and −786T>C polymorphisms are associated with reduced breast cancer risk.     

Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in caucasian women.

PURPOSE: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. Interleukin (IL)-1 and IL-6 are crucially involved in breast carcinogenesis. Whether polymorphisms of the genes encoding IL-1 (IL1) and IL-6 (IL6) also influence breast cancer risk is unknown. EXPERIMENTAL DESIGN: In the present case-control study, we ascertained three polymorphisms of the IL1 gene cluster [-889 C/T polymorphism of the IL1alpha gene (IL1A), -511 C/T polymorphism of the IL1beta promoter (IL1B promoter), a polymorphism of IL1beta exon 5 (IL1B exon 5)], an 86-bp repeat in intron 2 of the IL1 receptor antagonist gene (IL1RN), and the -174 G/C polymorphism of the IL6 gene (IL6) in 269 patients with breast cancer and 227 healthy controls using PCR and pyrosequencing. RESULTS: Polymorphisms within the IL1 gene cluster and the respective haplotypes were not associated with the presence and the phenotype of breast cancer. The IL6 polymorphism was significantly associated with breast cancer. Odds ratios for women with one or two high-risk alleles versus women homozygous for the low-risk allele were 1.5 (95% confidence interval, 1.04-2.3; P = 0.04) and 2.0 (95% confidence interval, 1.1-3.6; P = 0.02), respectively. No association was ascertained between presence of the IL6 polymorphism and various clinicopathologic variables. CONCLUSIONS: Although polymorphisms within the IL1 gene cluster do not seem to influence breast cancer risk or phenotype, presence of the -174C IL6 allele increases the risk of breast cancer in Caucasian women in a dose-dependent fashion.     

白细胞介素-10启动子区基因多态性与非霍奇金淋巴瘤相关性的研究

目的：探讨中国汉族人群白细胞介素－10基因（IL－10）启动子区－1082G／A、－819T／C和－592A／C基因多态性与非霍奇金淋巴瘤（NHL）发病的关系。方法：采用聚合酶链－限制性片段长度多态技术检测512例NHL患者和500名健康对照者IL－10启动予区－1082、－819和－592位点的基因型。结果：NHL组IL－10—1082位点AA、GA、GG基因型频率分别为85．7％、14．3％和0,对照组分别为88．8％、11．2％和0,两组相比差异无统计学意义,P〉0．05。－819位点与～592位点基因型具有高度连锁,－819TT／－592AA、819TC／～592AC和－819CC／－592CC基因型在NHI,组分别为45．9％、41．2％和12．9％,对照组分别为48．8％、40．8％和10．4％,两组相比差异无统计学意义,P〉0．05。对NHL亚型分析显示,各位点基因型在弥漫性大B细胞淋巴瘤（DLBCL）和滤泡性淋巴瘤（FL）病例组中与对照组相比,差异均无统计学意义,P〉0．05。单体型分析发现,上述位点具有4种单体型ATA、ACC、GCC和GTA,各单体型在NHL及其各亚型组与对照组之间的分布差异无统计学意义,P〉0．05。结论：中国汉族人群中IL－10启动子区－1082、－819和－592位点基因多态性及其单体型分布与NHL发病无相关性。     

One-carbon metabolism-related gene polymorphisms and risk of breast cancer

Environmental exposures and/or genetic background in Japanese population, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Folate plays an essential role in DNA methylation and synthesis, and thus may be involved in the development of breast cancer. Functional polymorphisms in genes encoding one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G) and thymidylate synthase (TS), influence folate metabolism, but epidemiological studies have yielded inconsistent findings. We therefore conducted a case-control study to clarify their associations with breast cancer risk. A total of 456 breast cancer cases and 912 age-matched and menopausal status-matched non-cancer controls were genotyped for the polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic models adjusted for potential confounders and gene-environment interactions between the polymorphisms and folate consumption were also evaluated. We observed an increased risk of postmenopausal breast cancer with the MTHFR 677TT genotype (OR = 1.83, 95% CI: 1.08-3.11) with a menopausal status-based analysis. In combination analysis, a significantly elevated OR was found among postmenopausal women with the MTHFR 677TT genotype and lower intake of dietary folate compared with those with 677CC genotype and adequate folate consumption (OR = 2.80, 95% CI: 1.11-7.07). In addition, interaction between the MTRR A66G polymorphism and folate intake for risk of postmenopausal breast cancer was observed (interaction P = 0.008). Our findings indicated that the MTHFR and MTRR polymorphisms were associated with individual susceptibility to breast cancer among postmenopausal women.     

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。     

Assessment of the associations between three VEGF polymorphisms and risk of prostate cancer

Vascular endothelial growth factor (VEGF) plays a crucial role in the regulation of angiogenesis and is involved in the development and metastasis of common cancers. There were several case–controls studies published to assess the associations of VEGF polymorphisms with risk of prostate cancer, but the findings were inconsistent. We performed a meta-analysis to provide a comprehensive assessment of the associations of three VEGF polymorphisms with risk of prostate cancer. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to assess the associations. Eleven individual case–control studies with a total of 5,209 cases of prostate cancer and 5,233 controls were finally included into our meta-analysis. Overall, VEGF rs833061 polymorphism was not associated with risk of prostate cancer (T versus C, OR?=?1.14, 95 % CI 0.91–1.44, P?=?0.26; TT versus CC, OR?=?1.09, 95 % CI 0.67–1.76, P?=?0.74; TT versus CC/CT: OR?=?1.46, 95 % CI 0.67–3.18, P?=?0.34; TT/CT versus CC, OR?=?1.08, 95 % CI 0.82–1.43, P?=?0.59). VEGF rs3025039 polymorphism was also not associated with risk of prostate cancer (T versus C, OR?=?1.03, 95 % CI 0.91–1.16, P?=?0.66; TT versus CC, OR?=?1.82 95 % CI 0.16–20.53, P?=?0.63; TT versus CC/CT, OR?=?2.00, 95 % CI 0.18–22.41, P?=?0.57; TT/CT versus CC, OR?=?0.72, 95 % CI 0.38–1.36, P?=?0.31). VEGF rs2010963 polymorphism was not associated with risk of prostate cancer under three models (C versus G, OR?=?1.17, 95 % CI 0.92–1.48, P?=?0.20; CC versus GG, OR?=?2.28, 95 % CI 0.90–5.75, P?=?0.08; CC versus GG/GC, OR?=?1.57, 95 % CI 0.67–3.68, P?=?0.30). In conclusison, current data suggest that those three VEGF polymorphisms are not obviously associated with risk of prostate cancer.     

P53 gene polymorphisms and breast cancer risk in Arab women

The association between polymorphisms in the p53 tumor suppressor gene and breast cancer risk has been studied in many human populations with conflicting conclusions. However, similar studies in Arab women are not available, and the status of these polymorphisms in this ethnic population is not known. We investigated the status of four known p53 gene polymorphisms and their possible role in breast cancer risk in Arab women. Genotyping was performed for 288 breast cancer women and 188 controls to determine Pro47Ser, Arg72Pro, Intron 3 Ins16 bp and intron 6 (G > C) polymorphisms. The p53 variant Pro47Ser was detected only in one Kuwaiti breast cancer patient and was not detected in any of the control subjects. Frequency of Arg/Arg at codon 72 was 26.6% in controls and 28.1% in patients, Arg/Pro frequency was 59.6% in controls and 69.4% in patients, the Pro/Pro genotype was 13.8% in controls and 2.4% in patients. We observed that women with Pro/Pro genotype have decreased risk for developing breast cancer (OR = 0.166, 95% CI = 0.067–0.411, p < 0.001). The intron 3 genotypes were A1/A1 (48.9%), A1/A2 (40.6%) and A2/A2 (10.5%) in controls and A1/A1(42.4%), A1/A2 (52.8%) and A2/A2 (4.8%) in cases. The intron 6 genotypes were 92.4% (GG), 7.6% (GC) and 0% (CC) in controls and 96.5% (GG), 3.5% (GC) and 0% (CC) in cases. No statistically significant differences between patients and controls were observed for intron 3 and intron 6 polymorphisms. Our data show that proline homozygosity at p53 codon 72 is associated with decreased breast cancer risk in Arab women.     

Quantitative assessment of the association between three polymorphisms in FAS and FASL gene and breast cancer risk

FAS and FAS ligand (FASL) play crucial roles in apoptotic signaling, and deregulation of this pathway may facilitate carcinogenesis. Studies on the association between the FAS/FASL polymorphisms (FAS-1377G/A rs2234767, FAS-670A/G rs1800682, and FASL-844C/T rs763110) and breast cancer risk have reported inconsistent results. Therefore, to characterize the relationship between those polymorphisms and breast cancer risk, we undertook a meta-analysis of those studies. Several electronic databases were searched for articles on the FAS/FASL polymorphisms and breast cancer risk. The genotype data were extracted; pooled odds ratios (OR) with 95 % confidence intervals (CIs) were used to estimate the strength of the association. Five studies were eligible for our meta-analysis. Overall, we observed significant associations of the FAS-1377G/A polymorphism with breast cancer susceptibility (AG vs. GG: OR?=?1.15, 95 % CI 1.02–1.30; AA vs. GG: OR?=?1.39, 95 % CI 1.12–1.72; AG/AA vs. GG: OR?=?1.18, 95 % CI, 1.16–1.32; A vs. G: OR?=?1.16, 95 % CI 1.06–1.26), but we did not observe significant association of the Fas-670A/G and FasL-844C/T polymorphisms with breast cancer risk. In the subgroup analysis, we observed that the FAS-1377G/A and FASL-844C/T polymorphisms were associated with breast cancer risk in Chinese but not Whites; we still did not observed association of the FAS-670A/G polymorphism with breast cancer risk. Our meta-analysis revealed that FAS-1377G>A polymorphism was associated with an increased risk of breast cancer. FASL-844C>T polymorphism might be associated with a reduced breast cancer risk in Chinese. However, FAS-670A/G had no any effect on breast carcinogenesis.     

Vitamin D receptor gene polymorphisms and breast cancer risk.

PURPOSE: The steroid hormone 1,25-dihydroxyvitamin D3 is thought to protect against breast cancer. The actions of 1,25-dihydroxyvitamin D3 are mediated via the vitamin D receptor (VDR), and a number of polymorphisms in the VDR gene have been identified. These result in distinct genotypes, some of which may alter susceptibility to breast cancer. We have investigated whether specific VDR gene polymorphisms are associated with breast cancer risk in a United Kingdom Caucasian population. EXPERIMENTAL DESIGN: In a retrospective case-control study, female breast cancer patients (n = 398) and control women (n = 427) were recruited, and three VDR polymorphisms were determined. RESULTS: The 3' VDR polymorphisms BsmI and variable-length poly(adenylate) sequence were both significantly associated with breast cancer risk; odds ratios (adjusted for age menopausal status and hormone replacement therapy usage) for bb genotype versus BB genotype = 1.92 (95% confidence interval, 1.20-3.10; P < 0.01) and for LL versus SS = 1.94 (95% confidence interval, 1.20-3.14; P < 0.01). A 5' VDR gene variant, FokI, was not associated with breast cancer risk when analyzed in isolation (P > 0.05). However, FokI did modulate the increased risk associated with the bb/LL genotype such that possession of one or more F alleles together with the bb/LL genotype augmented breast cancer risk. Furthermore, the highest proportion of bb and FFLL/FfLL genotypes occurred in women with metastatic breast cancer. CONCLUSIONS: VDR polymorphisms are associated with breast cancer risk and may be associated with disease progression. Additional investigations into how different genotypes may affect the functional mechanisms of the VDR will provide a better strategy for identifying women at risk of breast cancer and for developing improved treatments.     

IL-10基因多态性与肿瘤易感性的关系

白细胞介素-10(interleukin-10,IL-10) 是一种重要的免疫调节细胞因子,具有复杂的生物学活性,其基因存在基因多态性,这种多态性与多种肿瘤密切相关。通过临床和实验室研究发现在多种肿瘤中,IL-10基因的多态性与其表达量特征性升高有关。本文就近几年来多种肿瘤相关的IL-10基因多态性的研究进展作一综述。