Lack of association between let-7 binding site polymorphism rs712 and risk of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is characterized by its highly invasive and metastatic features. Therefore, screening genetic biomarkers of NPC to achieve early diagnose would be of great value for NPC therapy. Single nucleotide polymorphisms in let-7 miRNA binding site in 3′ untranslated region of KRAS mRNA have been found to be associated with various cancer risks. In this study, we genotyped the frequency of KRAS rs712 to test its effect on NPC risk in a hospital-based case–control study in a Chinese population, with 188 histologically confirmed NPC patients and 356 cancer-free controls, using polymerase chain reaction–restriction fragment length polymorphism assay. There was no significant difference in the genotype and allele frequencies of the rs712 polymorphism between the NPC patients and the control group (GT vs. GG, OR 0.83, 95 % CI 0.57–1.21; TT vs. GG, OR 1.27, 95 % CI 0.58–2.75). Our data suggest that the KRAS rs712 polymorphism in let-7 miRNA binding site has no association with NPC risk. Further experiments with larger sample size or other polymorphism sites are needed to verify the result, especially in different ethnic groups.     

Let-7靶基因KRAS结合区rs712多态性与脑胶质瘤发生相关性的研究

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。     

SMAD7 rs12953717 polymorphism contributes to increased risk of colorectal cancer

Mothers against decapentaplegic homolog 7 (SMAD7) rs12953717 polymorphism has been implicated to alter the risk of colorectal cancer (CRC), but the results are controversial. The objective of this study was to quantitatively evaluate the association between SMAD7 rs12953717 polymorphism and CRC susceptibility. A comprehensive search was conducted to identify all eligible studies of SMAD7 rs12953717 polymorphism and CRC risk. Pooled odds ratio and 95 % confidence interval were calculated using a fixed or random effects model. Statistical analysis was performed with Review Manager 5.0 and Stata 11. A total of 11 case–control studies, including 12,058 cases and 11,444 controls, were identified. The combined results based on all studies suggested that rs12953717 was associated with CRC risk under all genetic models. When stratifying for race, the data showed that the rs12953717 was associated with a significantly increased CRC risk under all genetic models in Caucasians. Statistically significant association was found in all genetic models except in recessive model comparison in the subgroup of Asians. After stratifying the studies by study design, there was a significant association between rs12953717 polymorphism and CRC risk under all genetic models in the subgroup of population-based studies. Our study suggests that rs12953717 polymorphism is associated with an increased CRC risk.     

A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk

Lung cancer is the leading cause of cancer deaths worldwide, yet few genetic markers of lung cancer risk useful for screening exist. The let-7 family-of-microRNAs (miRNA) are global genetic regulators important in controlling lung cancer oncogene expression by binding to the 3' untranslated regions of their target mRNAs. The purpose of this study was to identify single nucleotide polymorphisms (SNP) that could modify let-7 binding and to assess the effect of such SNPs on target gene regulation and risk for non-small cell lung cancer (NSCLC). let-7 complementary sites (LCS) were sequenced in the KRAS 3' untranslated region from 74 NSCLC cases to identify mutations and SNPs that correlated with NSCLC. The allele frequency of a previously unidentified SNP at LCS6 was characterized in 2,433 people (representing 46 human populations). The frequency of the variant allele is 18.1% to 20.3% in NSCLC patients and 5.8% in world populations. The association between the SNP and the risk for NSCLC was defined in two independent case-control studies. A case-control study of lung cancer from New Mexico showed a 2.3-fold increased risk (confidence interval, 1.1-4.6; P = 0.02) for NSCLC cancer in patients who smoked <40 pack-years. This association was validated in a second independent case-control study. Functionally, the variant allele results in KRAS overexpression in vitro. The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers and represents a new paradigm for let-7 miRNAs in lung cancer susceptibility.     

B7-H1基因rs4143815位点多态性与结直肠癌发病风险的关联研究

目的：B7-H1是肿瘤免疫治疗的一个靶点,位于其3'-非翻译区的rs4143815位点C/G多态性可影响其与miR-570的结合,进而影响B7-H1的表达。本研究旨在探讨B7-H1基因rs4143815位点多态性与结直肠癌发病风险的相关性。方法：采集215例结直肠癌患者和236例年龄性别匹配的健康对照人群外周静脉血,并收集手术切除结直肠癌和癌旁正常组织样本65例,直接测序法检测B7-H1基因rs4143815多态性,运用卡方检验分析B7-H1基因rs4143815多态性与结直肠癌发病风险的相关性;定量PCR检测B7-H1 mRNA表达。结果：结直肠癌和对照组中均检测到B7-H1基因rs4143815多态性的3种基因型,即CC、CG和GG基因型。结直肠癌和癌旁正常组织中均检测到B7-H1 mRNA的表达。与CC基因型相比,GG和CG/GG基因型显著增加了结直肠癌的发病风险[GG与CC相比：OR_调整=1.99,95% CI （1.19,3.34）,P=0.008;CG/GG与CC相比：OR_调整=1.58,95% CI （1.06,2.36） P=0.02]。与C等位基因相比,G等位基因显著增加了结直肠癌的发病风险[OR_调整=1.48,95% CI （1.14,1.93）,P=0.004]。B7-H1 mRNA在结直肠癌组织中的表达明显高于癌旁组织（P=0.02）,并且B7-H1基因rs4143815位点GG基因型携带者B7-H1 mRNA水平明显高于CC基因型携带者（P=0.03）。结论：B7-H1基因rs4143815位点GG基因型可能通过增加B7-H1 mRNA表达,进而增加了结直肠癌的发病风险。     

The effect of oxoguanine glycosylase 1 rs1052133 polymorphism on colorectal cancer risk in Caucasian population

Human oxoguanine glycosylase 1 (OGG1) is an important part of the base excision repair pathway in the DNA repair. Numerous epidemiological studies have evaluated the association between OGG1 rs1052133 polymorphism and the risk of colorectal cancer, but the results of these studies from the Caucasian population were conflicting. To derive a more precise assessment on the association between OGG1 rs1052133 polymorphism and risk of colorectal cancer in Caucasian population, we performed a meta-analysis. The odds ratios (OR) with 95 % confidence intervals (CI) were used to assess the strength of the association. Thirteen case–control studies with a total of 4,103 cases and 5,400 controls were finally included into the meta-analysis. Meta-analysis of all 13 studies showed that OGG1 rs1052133 polymorphism was significantly associated with the risk of colorectal cancer in Caucasian population (Cys versus Ser OR?=?1.20, 95 % CI?=?1.03–1.39, P?=?0.02; CysCys versus SerSer OR?=?1.44, 95 % CI?=?1.04–2.00, P?=?0.03; CysCys versus SerSer/SerCys OR?=?1.39, 95 % CI?=?1.15–1.67, P?=?0.0005). In the sensitivity analysis, omitting each study one at a time had no obvious influence on the pooled OR, which confirmed the stability of meta-analysis. The meta-analysis suggests that OGG1 rs1052133 polymorphism is significantly associated with the risk of colorectal cancer in Caucasian population     

微小RNA let-7与食管癌

微小RNA(miRNA)的发现为食管癌的诊断和治疗开辟了新的思路.let-7是目前研究最为广泛的miRNA之一,在多种肿瘤中表达下调.let-7能够靶向高迁移率蛋白A2 (HMGA2)从而抑制细胞增殖,发挥抑癌基因的作用.研究发现分化程度越低的细胞,let-7表达水平越低,其有望作为低分化肿瘤的标志.此外,let-7与食管癌放化疗敏感性也密切相关.     

Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population

Colorectal cancer (CRC) is among the major causes of cancer-related morbidity, mortality, and human health problem worldwide. Single-nucleotide polymorphisms (SNPs) in different genes are reported to be effective in increased risk of CRC in different ethnic population. We conducted a case–control study in patients diagnosed with sporadic colorectal cancer (n = 115) and healthy controls based on colonoscopy evidences (n = 120).In this replicative study, we aimed to investigate the association of two previously reported polymorphisms, rs6983267 and rs4444903, with sporadic colorectal cancer in a subset of Iranian patients. Genotyping was performed via polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. A significant relation was found between rs6983267 variant in the 8q24 region and colorectal cancer. The distribution of G/G genotypes among sporadic CRC patients was more frequent than that in the control group (P value = 0.001). The frequency of the G allele in the colorectal cancer patient group was also higher than that in the control group (65% vs. 48%; P value = 0.001). Compared with GG genotype, individuals with G/T and T/T genotypes had lower risk to develop sporadic CRC (OR = 0.357, 95% CI = 0.201–0.635). For the rs4444903 SNP, no significant association (P value = 0.149) was found with colorectal cancer risk. In conclusion, our findings suggest that the 8q24 rs6983267 SNP may play a pivotal role in the development of sporadic CRC in Iranian population. Therefore, it may be included as a potential genetic susceptibility marker for sporadic CRC.     

The TERT variant rs2736100 is associated with colorectal cancer risk

Background:

Polymorphic variation at the 5p15.33 (TERT–CLPTM1L) locus is associated with the risk of many cancers but a relationship with colorectal cancer (CRC) risk has yet to be defined.

Methods:

We used data from six genome-wide association studies (GWAS) of CRC, linkage disequilibrium mapping and imputation, to examine the relationship between 73 single-nucleotide polymorphisms at 5p15.33 and CRC risk in detail.

Results:

rs2736100, which localises to intron 2 of TERT, provided the strongest evidence of an association with CRC (P=2.28 × 10⁻⁴). The association was also shown in an independent series of 10 047 CRC cases and 6918 controls (P=0.02). A meta-analysis of all seven studies (totalling 16 039 cases, 16 430 controls) provided increased evidence of association (P=2.49 × 10⁻⁵; per allele odds ratio=1.07). The association of rs2736100 on CRC risk was shown to be independent of 15 low-penetrance variants previously identified.

Conclusion:

The rs2736100 association demonstrates an influence of variation at 5p15.33 on CRC risk and further evidence that the 5p15.33 (TERT–CLPTM1L) locus has pleiotropic effects (reflecting generic or lineage-specific effects) on cancer risk.     

A population-specific correlation between ADIPOQ rs2241766 and rs 1501299 and colorectal cancer risk: a meta-analysis for debate

Aims

Many epidemiological studies have investigated the correlation between adiponectin, C1Q and collagen domain containing (ADIPOQ) single nucleotide polymorphisms (SNPs) and risk of colorectal cancer (CRC). Although conflicting results have been reported, there was dispute regarding two SNPs (rs2241766 T/G and rs1501299 G/T). Therefore, we conducted a meta-analysis to systematically assess the associations and try to find the reasons for the dispute.

Methods

We searched PubMed, the Cochrane Library, Elsevier, Wiley Online Library, China National Knowledge Infrastructure, WanFang data and Chongqing VIP to search for all eligible case?control studies published up to January 2015. Effect sizes of odds ratios (OR) and 95 % confidence intervals (95 % CI) were calculated using a fixed- or random-effect model.

Results

Ten case–control studies including 4377 cases and 5584 controls were selected. A significant difference was observed in Chinese (OR 0.76; 95 % CI 0.68, 0.85; P < 0.001) and Ashkenazi Jewish populations (OR 0.79; 95 % CI 0.63, 0.99; P = 0.04) for rs2241766 with dominant model (TT vs TG + GG). A significant difference was observed in the Chinese population (OR 1.23; 95 % CI 1.11, 1.37; P < 0.001) for rs1501299 with dominant model (TT vs TG + GG). In addition, intake of red meat showed a synergistic effect between ADIPOQ gene and risk of colorectal cancer (CRC).

Conclusions

ADIPOQ SNPs rs2241766 T/G and rs 1501299 G/T have a population-specific correlation with risk of CRC. However, small sample studies may increase reporting bias, particularly if the total number of studies included in the analysis is small.

     

CYP1A2 rs762551 polymorphism contributes to risk of lung cancer: A meta-analysis

Previous studies proposed that CYP1A2 rs762551 polymorphism might be associated with risk of lung cancer by influencing the function of CYP1A2. However, previous studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer reported inconsistent findings. We performed a meta-analysis of the published case–control studies to assess the association between CYP1A2 rs762551 polymorphism and risk of lung cancer. PubMed and Embase were searched to identify relevant studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer, and seven studies with a total of 3,320 subjects were finally included into the meta-analysis. The pooled odds ratio (OR) and 95 % confidence interval (95%CI) was calculated to evaluate the association. Meta-analysis of total studies showed that CYP1A2 rs762551 polymorphism contributed to risk of lung cancer under all four genetic models (C versus A: OR?=?1.26, 95%CI 1.13 to 1.40, P?<?0.001; CC versus AA: OR?=?1.61, 95%CI 1.28 to 2.04, P?<?0.001; CC versus AA/AC: OR?=?1.52, 95%CI 1.11 to 2.09, P?=?0.009; CC/AC versus AA: OR?=?1.28, 95%CI 1.10 to 1.48, P?=?0.001). Subgroup analysis based on ethnicity further suggested that CYP1A2 rs762551 polymorphism was associated with risk of lung cancer in Caucasians. These results from the meta-analysis suggest that CYP1A2 rs762551 polymorphism contributes to risk of lung cancer.     

维生素 C 对 KRAS 突变型结直肠癌的治疗作用

摘要：目的 总结维生素 C 在治疗含有 KRAS、 BRAF 突变基因的结直肠癌中的研究结果,归纳分析其抗肿瘤的生理机制。 方法 以维生素 C、结直肠癌作为主题词,在 CNKI 和 PubMed 中查阅相关文献,并对结果进行归纳总结。 结果 结合肿瘤 细胞代谢特点和活性氧对肿瘤细胞的影响,发现维生素 C 可以伴随 KRAS、 BRAF 突变基因导致的糖酵解活动的升高被而 被转运到细胞内,导致细胞内不平衡的氧化还原态,使细胞供能受阻,从而饥饿肿瘤细胞,来达到抗肿瘤的作用。 结论 注 射大剂量维生素 C 可以抑制小鼠体内含 KRAS、 BRAF 突变基因的结直肠肿瘤的生长,这一发现可能指导未来临床试验。     

An updated meta-analysis of the association between ADIPOQ rs2241766 polymorphism and colorectal cancer

Adiponectin (ADIPOQ) is a cytokine produced by adipose tissue involved in carcinogenesis. ADIPOQ SNP rs2241766 has been extensively studied in colorectal cancer (CRC) community with contentious and conflicting conclusions. The objective of this study was to comprehensively assess the association between SNP rs2241766 and CRC risk. PubMed, Embase, CNKI, as well as the references of the retrieved articles were searched to identify the eligible studies for this meta-analysis. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the association. We also examined the heterogeneity and publication bias and performed sensitivity analyses. Seven studies with 2,414 cases and 2,796 controls together did not show any significant association between SNP rs2241766 and CRC risk. Subgroup analyses by ethnicity and sample size also failed to provide statistically significant evidence. This meta-analysis demonstrates that ADIPOQ SNP rs2241766 may not represent as an effect modifier for the risk of CRC.     

Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk

Human cellular glutathione peroxidase 1 (hGPX1) is a selenium-dependent enzyme that participates in the detoxification of hydrogen peroxide and a wide range of organic peroxides. We conducted a case-control study nested within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort to evaluate the association between the proline to leucine polymorphism at codon 198 of hGPX1 and lung cancer risk. Cases (n = 315) were matched to controls on age (+/-5 years), intervention group, and study clinic using incidence density sampling in a 1:1 ratio. The prevalence of the hGPX1 Pro198Leu variant allele was 58% for controls and 71% for cases (P < 0.001). Using conditional logistic regression, we found a significant association between hGPX1 genotype and lung cancer risk. The odds ratio for heterozygotes was 1.8 (95% confidence interval, 1.2-2.8) and 2.3 (95% confidence interval, 1.3-3.8) for homozygous variants compared to wild-type individuals. Due to its high prevalence, the hGPX1 variant may contribute significantly to lung cancer risk among Caucasians but not among ethnic Chinese who do not exhibit this polymorphism.     

APE1 rs1760944基因多态性与中国人群癌症易感风险关系的Meta分析

目的：在DNA的碱基切除修复过程中脱嘌呤/脱嘧啶核酸内切酶1（APE1）起至关重要的作用。流行病学研究发现 APE1 rs1760944基因多态性与致癌风险存在关联。本研究旨在评估中国人群中 APE1 rs1760944基因多态性与致癌风险之间的关系。方法：检索PubMed、ISI Web of Knowledge、中国知网数据库、万方数据库2013年11月以前符合条件的相关病例对照研究。比值比（OR）和95%可信区间（95%CI）用作评估关联强度的大小。结果：共纳入11个有关APE1 rs1760944基因型和致癌风险的病例对照研究,共计5652例癌症患者和6008例对照。分析结果显示,在任何遗传模式中,APE1 rs1760944基因多态性与降低致癌风险显著相关（纯合子对比：OR=0.71,95%CI=0.63-0.79;杂合子对比：OR=0.86,95%CI=0.79-0.94;显性模型：OR=0.80,95%CI=0.74-0.87;隐性模型：OR=0.78,95%CI=0.71-0.86）。另外,在肺癌的研究中也发现同样结论（纯合子对比：OR =0.68,95%CI=0.59-0.79;杂合子对比：OR=0.86,95%CI=0.77-0.98;显性模型：OR=0.80,95%CI=0.72-0.90;隐性模型：OR=0.77,95%CI=0.68-0.87）。结论：在中国人群中,APE1 rs1760944基因多态性可能降低癌症的易感性。     

GPC5 rs2352028 polymorphism and risk of lung cancer in Han Chinese

rs2352028 in GPC5 has been reported to be associated with the risk of lung cancer in never-smokers. We performed a replication study in 1,045 lung cancer patients and 1,094 controls of Han Chinese origin. We found no association between rs2352028 and lung cancer/adenocarcinoma in never-smokers, but a p value of .04 (under the recessive model) was obtained between this SNP and overall lung cancer/adenocarcinoma. Our data and a recent meta-analysis suspected the possibility of rs2352028 being a risk variant of lung cancer risk in never-smokers. Our findings suggested that rs2352028 might confer a slight risk to lung cancer/adenocarcinoma.