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1.
The pathogenesis of chronic obstructive pulmonary disease (COPD) is not fully understood, and environment and genetic factors have been investigated. Moreover, cytokine genes play an important role in COPD pathogenesis. However, the molecular mechanism of COPD induced by the factors is still unknown. The present study was undertaken to clarify a role of interleukin (IL)-12 16974A/C and IL-27 4730T/C, -964A/G, and 2905T/G polymorphisms in Chinese subjects with COPD. Polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) and sequence analyses were used to type IL-12 and IL-27 polymorphisms in 120 patients with COPD and 100 healthy controls. There were significant differences in the genotype and allele distribution of -964A/G and 2905T/G polymorphisms of the IL-27 gene among cases and controls in a Chinese population. When compared with the control group, subjects with AG genotype of the IL-27 -964A/G had a 2.22-fold decreased risk of COPD (odds ratio [OR] = 0.450, 95% confidence interval [CI]: 0.245-0.826; p = 0.009), and subjects with TG genotype of the IL-27 2905T/G had a 2.85-fold decreased risk of COPD (OR = 0.351, 95% CI: 0.137-0.899; p = 0.024). Compared with the TAT haplotype, the TGG haplotype was associated with a significantly decreased risk of COPD (OR = 0.29, 95% CI: 0.108-0.784; p = 0.010). Even after Bonferroni corrections, significant associations with COPD were observed for the AG genotype of the IL-27 -964A/G and the TGG haplotype of the IL-27 gene. Our data suggest that polymorphisms in the IL-27 gene may play a role in the development of COPD in Chinese population. 相似文献
2.
AbstractObjective: To investigate the association of caveolin-1 (CAV1) genetic variants (C239A (rs1997623), G14713A (rs3807987), G21985A (rs12672038), T29107A (rs7804372)) with esophageal squamous cell carcinoma (ESCC) susceptibility. Methods: A total of 427 patients with ESCC and 427 healthy controls were genotyped using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Results: There were significant differences between patients and controls in distributions of their genotypes and allelic frequencies in G14713A and T29107A polymorphisms. Furthermore, haplotype analysis revealed that haplotypes CAAT and CAGT were associated with high risk for ESCC, while haplotype CGGA was protective against ESCC. Stratified analysis showed the associations between the SNPs (G14713A and T29107A) and ESCC risk were noteworthy among female patients and patients who never smoke or drank alcohol. Conclusions: Genetic polymorphisms of CAV1 G14713A and T29107A might affect an individual’s susceptibility in developing ESCC, making them efficient potential genetic biomarkers for early detection of ESCC. 相似文献
3.
The potent tumor suppressors P16 and RB1 are the key regulators of cell cycle machinery in eukaryotes. Polymorphisms in these
genes play an important role in the outcome of various diseases including cancer. In the present study, we evaluated the association
of p16 and RB1 polymorphisms with cervical cancer susceptibility in Indian population. We screened 150 histologically confirmed
cervical cancer cases along with equal number of healthy controls with normal cervical cytology. PCR-RFLP method was employed
for genotyping of SNPs in p16 C540G (rs11515), C580T (rs3088440) in the 3′-UTR of exon 3 and RB1 A153104G (rs4151580) located
in the intron 18 and confirmed by direct sequencing. Both patients and controls were screened for HPV infection. In this case–control
study 84.67% (127/150) of cases were found to be positive for HPV DNA sequence. Women carrying p16 C540G carrier genotypes
540 (CG/GG) may have protective effect for the development of cervical cancer ( P = 0.0001, OR = 0.31, 95% CI = 0.17–0.56). And SNP at C580T of p16 gene was found to be negatively associated with the risk
of cervical cancer ( P = 0.0004, OR = 0.04, 95% CI = 0.002–0.63). p16 (540C/580T) has emerged as a major risk haplotype ( P = 0.033, OR = 1.47, 95% CI = 1.05–2.07) whereas p16 (540G/580T) as a chief protective haplotype ( P = 0.014, OR = 0.39, 95% CI = 0.18–0.83) for the development of cervical cancer among Indian women. Contrary to this, SNP
at A153104G of RB1 gene showed statistically significant association ( P = 0.035, OR = 1.69, 95% CI = 1.06–2.68) with increased susceptibility for the development of cervical cancer. Our results
suggest that single nucleotide polymorphisms in p16, RB1 genes may affect the susceptibility to cervical cancer collectively. 相似文献
4.
Tumor necrosis factor alpha (TNF-α) is a vital cytokine involved in inflammation, immunity, and cellular organization. The
TNFA-308G/A (rs1800629) and -238G/A (rs361525) polymorphisms are two widely investigated variants for their associations with
risk of cervical cancer, but the results are conflicting. Here, we performed a meta-analysis to pool the data and evaluate
the between-studies heterogeneity. All the case–control studies published from January 1989 to October 2010 on the association
between the two polymorphisms of TNFA and cervical cancer risk were identified by searching the electronic literature Medline. The cervical cancer risk associated
with the two polymorphisms of TNFA gene was estimated for each study by OR together with its 95% CI, respectively, by using the Review Manager 4.2 software. It was showed that the variant homozygote
-308AA was associated with a significantly increased risk of cervical cancer (AA vs. GG: OR = 1.41, 95% CI = 1.03–1.92, P = 0.033; AA vs. GA/GG: OR = 1.39, 95% CI = 1.02–1.90, P = 0.036), and the effect was more evident among Asians (AA vs. GA/GG: OR = 3.67, 95% CI = 1.25–10.81, P = 0.018). We also found that the variant genotypes -238GA/AA was associated with a significantly decreased risk of cervical
cancer (GA/AA vs. GG: OR = 0.55, 95% CI = 0.41–0.74, P < 0.001). The results suggested that TNFA-308G/A and -238G/A may contribute to cervical cancer susceptibility. 相似文献
5.
Context: Polymorphisms of IL-32 related closely to tumoregenesis. Materials and methods: Two IL-32 polymorphisms (rs12934561 and rs28372698) and mRNA expression were conducted by SNP genotype assay and real-time PCR in 423 lung cancer patients and 437 controls. Results: T allele of rs28372698 associated significantly with poor prognosis in moderate and well-differentiated lung cancer patients. TT genotype of rs12934561 related closely to poor survival status in squamous carcinoma. IL-32 mRNA expression decreased in lung cancer. Discussion and conclusion: Our study indicates the importance of IL-32 polymorphism and mRNA expression in susceptibility and influence of survival status in lung cancer. 相似文献
6.
This study investigated the association between IL-27 gene polymorphisms and susceptibility to epithelial ovarian cancer in a Chinese population and discusses the risk factors associated with survival time. We collected data on 229 patients diagnosed with epithelial ovarian cancer, from 15 to 77 years of age with a long clinical follow-up period. Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the genotype of IL-27 gene polymorphisms. Ovarian cancer-specific survival (OCSS) according to genotype of IL-27 gene polymorphisms was explored by Kaplan–Meier analysis and Cox proportional hazards modeling. Significant differences for genotype frequencies of both SNP sites were found between cases and controls. Both allele G frequencies were significantly greater among the cases (rs153109: 0.404 vs. 0.303, P = 0.001, odds ratio [OR]?=?1.333, 95% confidence interval [CI]?=?1.133–1.567; rs17855750: 0.146 vs. 0.083, P = 0.001, OR?=?1.766, 95% CI?=?1.258–2.481). Haplotype analysis showed haplotypes AG, GT and GG were associated with increased ovarian cancer susceptibility while AT was a protective haplotype. Advanced FIGO stage (stages III?+?IV) and non-optimal cytoreductive surgery (residual tumor ≥1 cm) were poor prognostic factors in the univariate analysis ( P = 0.003, P = 0.049). However, FIGO stage was found to be the only independent significant prognostic factor by Cox proportional hazards analysis ( P = 0.042). IL-27p28 mRNA expression was significantly decreased in ovarian cancer patients ( P?<?0.0001), while no significant relationship was found between IL-27p28 mRNA expression and polymorphism of rs153109 and rs17855750 ( P?=?0.193 and P?=?0.146, respectively). Our study suggests that IL-27 gene polymorphisms may be involved in the susceptibility to epithelial ovarian cancer, but not in survival in a clinic-based Chinese population. Haplotype analysis of these two SNPs seems to be an important mark to predict the disease susceptibility. Advanced FIGO stage, as the only significant, independent risk factor, predicts poor clinical outcomes for patients diagnosed with epithelial ovarian cancer. The decreased expression of IL-27p28 mRNA in ovarian cancer might indicate the antitumor activities of this novel cytokine. 相似文献
7.
Xeroderma pigmentosum group G ( XPG) protein plays an important role in the DNA repair process by cutting the damaged DNA at the 3′ terminus. Previous studies have indicated some polymorphisms in the XPG gene are associated with stomach cancer susceptibility. We performed this hospital‐based case–control study to evaluate the association of four potentially functional XPG polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C and rs873601G>A) with stomach cancer susceptibility. The four single nucleotide polymorphisms (SNPs) were genotyped in 692 stomach cancer cases and 771 healthy controls. Logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association of interest. Of the studied SNPs, XPG rs873601G>A polymorphism was found to significantly associate with stomach cancer susceptibility (AA versus GG/AG: OR = 1.31, 95% CI = 1.03–1.66, P = 0.027). Combined analysis of all SNPs revealed that the individuals with two of risk genotypes had a significantly increased stomach cancer risk (OR = 1.52, 95% CI = 1.13–2.06). In the stratification analysis, the association between the rs873601AA genotype and stomach cancer risk was observed in older group (>59 year), as well as patients with non‐cardia stomach cancer. Further combined analysis indicated men, smokers, or non‐drinkers more than one risk genotypes had a significantly increased stomach cancer risk. Our results indicate that XPG rs873601G>A polymorphism may be associated with the risk of stomach cancer. Further prospective studies with different ethnicities and large sample sizes are needed to validate our findings. 相似文献
8.
Cervical cancer is emerging as a leading cause of morbidity and mortality in women worldwide. Toll-like Receptor (TLR) gene
polymorphisms may contribute to subsequent inter-individual variability in cancer susceptibility. The present study aimed
to identify the role of TLR 3 (c.1377C/T) [rs3775290] and TLR 9 (G2848A) [rs352140] gene polymorphisms in the risk of developing
cervical cancer in North India. Peripheral blood samples were collected from 200 histopathologically confirmed cervical cancer
patients from North India and 200 unrelated, cancer-free, age-matched healthy female controls of similar ethnicity. Genomic
DNA was extracted using the salting-out method, and genotyped for TLR 3 and TLR 9 using polymerase chain reaction-based restriction
fragment length polymorphism (PCR-RFLP). Our data demonstrated a lack of association between TLR 3 (c.1377C/T) and TLR 9 (G2848A)
gene polymorphisms and the risk of developing cervical cancer. TLR 3 CT + TT was marginally associated ( P = 0.061; age-adjusted OR = 1.46; 95% CI = 0.98–2.16) with cervical cancer susceptibility. The AA genotype of TLR 9 showed
borderline significance ( P = 0.053) conferring a marginal increased risk (OR = 2.63, 95%CI = 0.99–7.01) for advanced cancer stages (III + IV). Further,
TLR 3 and 9 polymorphisms did not have a significant role in modulation of risk due to tobacco usage in cervical cancer patients.
Our study suggests only marginal role of TLR 3 and 9 gene polymorphisms in cervical cancer susceptibility in North India;
however, future studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity
in cervical cancer etiology in women worldwide. 相似文献
9.
AbstractObjective: We investigated the clinical significance of ERp57 in the progression of cervical cancer. Methods: mRNA and protein expression of ERp57 in cervical neoplasias were examined. Results: ERp57 mRNA expression was significantly decreased in cervical cancers. Immunohistochemistry revealed that ERp57 expression in 123 cervical cancers was down-regulated compared to cervical intraepithelial neoplasias or normal tissues ( p?<?0.001). Low ERp57 expression was significantly associated with worse overall survival (HR?=?12.19, p?=?0.018). Conclusions: Low ERp57 expression independently predicts a poor outcome for patients with cervical cancer, supporting the notion that ERp57 may be a promising novel cancer target. 相似文献
10.
ObjectiveInterleukin-1 beta (IL-1β) is a crucial cytokine that has been implicated in cancer and metastasis development. However, its possible mechanistic role in cervical cancer remains unclear. This study aimed to investigate the functions of exogenous IL-1β in cervical cancer cell proliferation and migration. MethodsHeLa cell proliferation and migration were measured using MTT and Transwell assays. A lentivirus-mediated packaging system was used to construct an IL-1β overexpressing cell line. MEK/ERK signal transduction was inhibited by pretreatment with the MEK inhibitor PD98059. qRT–PCR and Western blotting were used to test the expression of relevant genes. ResultsExogenous IL-1β promoted the proliferation and migration of HeLa cells. In addition, overexpression of IL-1β in HeLa cells promoted cell proliferation. Mechanistically, exogenous IL-1β increased the phosphorylated MEK and ERK levels in HeLa cells and the expression of JUN, RELB, and NF-κB2. Alternatively, blockade of MEK inhibited the promoting proliferation effects of IL-1β and the expression of JUN, RELB, and NF-κB2. ConclusionsOur data suggest that exogenous IL-1β regulates HeLa cell functions by regulating the MEK/ERK signaling pathway and by targeting JUN, RELB, and NF-κB2. Our study uncovered a potential association across IL-1β, cervical tumor development, and cancer progression. 相似文献
11.
Lung cancer is one of the leading causes of death from cancer. Both immune cells and tumor cells play a key role in lung cancer
immunity by secretion of cytokines and developing type-2 cell-mediated immune response. IL-13 is an immunoregulatory cytokine
affecting tumor immunosurveillance by deviation of immune response from Th1 to Th2. In the present study we sought to determine
the association of single nucleotide polymorphisms (SNPs) of IL-13 gene at positions +2044 (G/A) and −1055 (C/T) and lung cancer. One hundred forty one patients and 113 controls were recruited;
control group was subdivided into smoker and nonsmoker individuals for serum detection. Genotyping was carried out by PCR-RFLP
assay and IL-13 detection by ELISA method. No statistically significant difference was found in the frequency of genotypes,
alleles, and haplotypes at positions +2044 (G/A) and −1055 (C/T) of IL-13 gene between lung cancer patients and controls. Serum level of IL-13 was not detectable in both groups. The results of this
study reveal that although +2044 (G/A) and −1055 (C/T) SNPs in IL-13 are implicated in some pulmonary processes, they do not confer susceptibility to lung cancer in Iranian population. 相似文献
13.
Earlier studies suggest that end-stage renal disease (ESRD) is associated with inflammatory state and have become a major
cause of morbidity and mortality worldwide. This study speculated the role of interleukins (IL)-2, -4, and -6 cytokines gene
polymorphism with risk of susceptibility to ESRD. Polymorphism in IL-2 (−330 T/G, polymerase chain reaction [PCR]-restriction
fragment length polymorphism), IL-4 (intron-3, variable number of tandem repeat, variable number tandem repeats analysis),
and IL-6 (-174 G/C, amplification refractory mutation system, i.e. ARMS-PCR) were genotyped in 193 ESRD patients and 180 controls.
Significant difference was observed in genotype frequencies of IL-4 and IL-6 between ESRD patients and control group ( p < 0.001 and p = 0.032, respectively). Patients had higher frequency of homozygous B2B2 genotype (IL-4) than controls (62.7% vs 46.7) and
GG genotype of IL-6 (73.1% vs 60.6%). The genotypic frequencies of IL-2 were comparable in patients and controls ( p = 0.102). Significant association of IL-4 was also observed in patients with glomerulonephritis ( p = 0.001). Combination of low IL-4 and high IL-6 genotypes were significantly associated with ESRD showing the highest risk,
i.e. >threefolds risk (odds ratio=3.48, 95%CI=1.88–6.42; p < 0.001) among the four possible combinations taking high IL-4 and low IL-6 as reference. Our study suggests that polymorphism
in IL-4 and IL-6 may be associated with susceptibility to ESRD. Further, combined analysis implicated a higher risk in ESRD
patients with low IL-4 and high IL-6 producing genotypes. This study provided the basis for defined anti-inflammatory approaches
to limit renal disease progression. 相似文献
14.
Interleukin-13 (IL-13) is a TH2 cytokine with direct and indirect immunoregulatory functions on cancer cells. The cytokine
has been reported to have some polymorphic variations at the gene level associated with some immune related diseases including
asthma and allergy. In the present study, association of three IL13 gene polymorphisms at positions −1512 A/C and −1055 C/T in the promoter and +2044 G/A in exon-4 was investigated in Iranian
women with breast cancer and healthy controls. Genotyping of IL13 gene polymorphisms were performed by PCR–RFLP methods. Serum level of IL-13 was assessed by ELISA. Haplotypes were constructed
from genotypic data using Arlequin 3.1 software package. Haplotype analysis revealed higher frequency of a three-locus haplotype,
ACA (−1512A/−1055C/+2044A), in normal women than breast cancer patients ( P < 0.025). Haplotype CCA, from the other hand, was observed with more frequency among patients than controls ( P < 0.03). No statistically significant differences were found in the frequency of genotypes and alleles between patients and
control group. No association was observed between investigated genotypes and other prognostic factors including tumor type,
lymph node involvement and tumor size. IL-13 serum level was undetectable in both patients and control subjects. Despite observing
no association between breast cancer and the single SNPs, results of this investigation suggest that the presence of CCA haplotype
of IL13 gene may be associated with susceptibility of Iranian women to breast cancer. 相似文献
15.
Cancer cervix is one of the leading causes of cancer-related mortality among women worldwide. It is believed that the host genetic factors such as inflammation-induced cytokines may play a role in cervical carcinogenesis. The interleukin-1β (IL-1β) gene contains several single nucleotide polymorphisms. One of them, C-511T, which in the promoter region has been associated with increased IL-1β production and with increased risk of developing cancers. We assessed the association between the IL-1β C-511T polymorphism and cervical cancer risk in a case-control study among 100 histopathologically confirmed Egyptian women with cervical cancer and 50 age-matched, cervical cytology negative, healthy controls by polymerase chain reaction-restriction fragment length polymorphism. Plasma levels of IL-1β were assayed by enzyme-linked immunosorbent assay. There was significant increase in the mean plasma IL-1β level in cervical cancer cases (43.40 ± 25.95 pg/ml) when compared with controls (30.51 ± 18.28 pg/ml, P = 0.002). The plasma levels above the 75th percentile of controls (IL-1β ≥ 45.74 pg/ml) were significantly associated with a 2.49-fold increased risk of cervical cancer. The significant increase in IL-1β concentration in cervical cancer cases was observed only among cervical cancer cases carrying C-511T variant genotypes. T/T genotype of IL-1β polymorphism was significantly higher in cervical cancer cases compared with controls (57 vs. 38%; OR = 2.16; P = 0.028) and the T allele carriage was significantly associated with cervical cancer risk (OR = 2.00, 95% CI = 1.19-3.38, and P = 0.008). In conclusion, plasma IL-1β level and IL-1β C-511T polymorphism may be considered as candidate biomarkers for cervical cancer in Egyptian women. 相似文献
16.
AbstractObjective: To determine the relationships between variants in adiponectin gene ( ADIPOQ) with advanced forms of age-related macular degeneration (AMD) susceptibility. Methods: A total of 189 advanced AMD patients and 168 controls were recruited. Seven tagging single-nucleotide polymorphisms in ADIPOQ were genotyped by the SNaPshot method. Results: Alleles or genotypes of rs822396 distributed significantly differently in advanced AMD patients and controls. The minor allele G at rs822396 was associated with an increased risk of advanced AMD in a dominant model. Furthermore, haplotype analysis revealed that haplotypes AGGACCT and TGACCCC were significantly increased the advanced AMD susceptibility, whereas haplotypes AGAACGC, TGAACGT and TGACAGC had protective effects. Conclusion: ADIPOQ genetic variant rs822396 might affect an individual’s susceptibility to AMD, making it efficient genetic biomarkers for early detection of AMD. 相似文献
17.
目的:研究高海拔地区藏族妇女宫颈组织中P21Ser31Arg的多态性,并分析其与宫颈癌遗传易感性的相关性。方法:选择2015年7月~2016年6月收治的200例宫颈癌患者、100例宫颈上皮内瘤样病变(CIN)患者、100例宫颈炎患者及100例正常宫颈患者为研究对象,采用限制性酶切片段长度多态性分析(PCR-RFLP)方法检测各组患者宫颈组织中P21Ser31Arg三种基因型Ser/Ser、Ser/Arg及Arg/Arg的分布情况并比较其构成差异,进一步分析其多态性与宫颈癌患者年龄、癌症分型及分化程度的相关性。结果:四组患者宫颈组织中均检测到三种基因型,Ser/Arg、Ser/Ser及Arg/Arg三种基因型的构成比分别为53.38%、34.88%及11.75%。四组患者宫颈组织中P21Ser31Arg的三种基因型分布整体比较及各组两两比较,差异均无统计学意义(P0.05)。200例宫颈癌患者中,不同年龄组及不同分型组患者的P21Ser31Arg基因型分布比较,差异无统计学意义(P0.05);而不同分化程度组浸润性鳞癌患者的三种基因型分布比较,差异具有统计学意义(P0.05)。结论:未发现P21Ser31Arg多态性与高海拔地区藏族妇女宫颈癌的遗传易感性有关,而可能与宫颈癌患者的分化程度相关。 相似文献
18.
Background: Data from previous studies on the role of inflammatory cytokines as biomarkers for diabetic kidney disease (DKD) are contradictory. The association of a particular inflammatory cytokine single nucleotide polymorphism (SNP) with susceptibility to DKD has not been consistently replicated. We aimed to investigate the utility of inflammatory cytokines as biomarkers for DKD in type 2 diabetes mellitus (T2DM) patients. Association of inflammatory cytokine gene SNPs with the development of DKD was also explored. Subjects and Methods: One hundred and fifty-nine Kuwaiti subjects were recruited in this study, including 50 T2DM patients without DKD, 67 diabetic DKD patients and 42 healthy subjects. Plasma levels of interleukin-6 (IL-6), IL-10, interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were measured by enzyme-linked immunosorbent assays. Nine SNPs, including 2 SNPs in IL-6, 3 SNPs in IL-10, 1 SNP in IFN-γ and 3 SNPs in TNF-α, were genotyped using TaqMan SNP genotyping assays. Results: Diabetic DKD patients showed higher IL-6, IL-10, IFN-γ and TNF-α levels than those without DKD. Diabetic DKD patients had a significantly higher frequency of IL-10???1082?A allele than those without DKD (p?=?0.001). No significant association of IL-6???174/?597 haplotypes with DKD risk was detected (p?=?0.188). Distribution of IL-10???592/?819/?1082 haplotypes differ significantly between T2DM patients with/without DKD (p?=?0.014). Diabetic DKD patients had a significantly lower frequency of IL-10???592C/?819C/?1082G haplotype than those without DKD (p?=?0.002). Conclusions: Although inflammatory cytokine genotypes and, more importantly, haplotypes may have the potential to identify those patients at risk of DKD, hence, improving DKD predisposition prediction, further investigations regarding their real clinical significance is warranted in a large cohort of patients. 相似文献
19.
AbstractContext and objective: The findings showed that the low-affinity IgE receptor plays a pivotal role in allergic immune response and it is a pharmacogenetic predictor in asthma disease. This study aims to investigate the association of genetic variations: rs28364072 and rs7249320 with asthma and its severity in north Indian children. Methods: Case-control-based genetic association study was performed among 550 children. Results: Statistical analysis demonstrated significant association between asthma and genotypes frequency of both the SNPs. Conclusions: Our data indicate that the studied variations are strongly associated with asthma susceptibility and might be risk factor among north Indian asthmatic children. 相似文献
20.
AbstractThis study aims to evaluate whether the c.1471G?>?A and c.1686C?>?G genetic polymorphisms of XRCC1 gene influencing gastric cancer susceptibility. A total of 813 subjects with Chinese Han ethnicity were enrolled. Our data suggest that the allele and genotype frequencies are significantly different from gastric cancer patients with cancer-free controls. We find that c.1471G?>?A and c.1686C?>?G genetic polymorphisms statistically increase the risk of gastric cancer. Our findings indicate these two genetic polymorphisms are related with the susceptibility to gastric cancer, and could be used as molecular markers for detecting gastric cancer in Chinese Han ethnicity. 相似文献
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