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Objective This study aims to investigate the significance of combined detection of HER2 gene amplification and chemosensitivity in gastric cancer. Methods Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and fluorescence reverse-transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of HER2 protein, HER2 gene amplification and the mRNA expression of ERCC1, TUBB3 and TYMS genes in 135 cases of gastric carcinoma. Results The expression rate of HER2 protein was 39.3% (53/135). Among these positive cases, patients with HER2 protein (3+) accounted for 9.6% (13/135), patients with HER2 protein (2+) accounted for 13.3% (18/135), and patients with HER2 protein (1+) accounted for 16.3% (22/135). The amplification rate of the HER2 gene was 35.8% (19/53). In the detection of the mRNA expression of ERCC1, TUBB3 and TYMS, 45 patients had low and moderate single gene expression, 50 patients had low and moderate double gene expression, 22 patients had low and moderate mRNA expression for ERCC1, TUBB3 and TYMS, and 18 patients had no low and moderate expression. Among the 53 patients with HER2 protein expression and 22 patients with low and moderate mRNA expression of ERCC1, TUBB3 and TYMS, 12 patients received chemotherapy and trastuzumab. Follow-up results revealed that HER2 gene status was positively correlated with the therapeutic effect of the combined treatment in patients with low mRNA expression of ERCC1, TUBB3 and TYMS. Among these patients, five patients with extensive HER2 (3+), HER2 cluster-specific amplification, and low mRNA expression of ERCC1, TUBB3 and TYMS had a total survival of up to 19.1 months. Conclusions The detection of HER2 in gastric cancer is highly heterogeneity, and the combined detection of HER2 protein expression, HER2 gene amplification and chemosensitivity can provide important reference markers for the benefit of antitumor drugs.

Gastric cancer (GC) is one of the most common malignant tumors in the world. As anti-angiogenic therapy shows efficacy in the treatment of GC, but only works in certain patients, the identification of potential beneficiaries are urgently required in order to apply appropriate treatments. The Lauren classification demonstrates numerous differences in etiology, epidemiology and pathology; however, the association between Lauren classification and pro-angiogenic factors remains unclear. The present study aimed to investigate the clinicopathological factors associated with Lauren classification and the prognostic significance of Lauren classification and vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) expression in GC. Paraffin-embedded GC tissues and clinical information of 255 patients with GC were collected. The clinicopathological factors associated with Lauren classification were evaluated by Logistic regression analysis. Kaplan-Meier survival and Cox regression analyses were used to examine the prognostic significance of Lauren classification and of VEGF and VEGFR-2 expression in patients with GC. The results demonstrated that there was no association between Lauren classification and VEGF and VEGFR-2 expression. Furthermore, results from survival analysis demonstrated that Lauren classification (P=0.001) and Tumor-Node-Metastasis stage (stage II, P=0.002; stage III, P

Summary Background The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. Methods In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0–3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with 125 iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. Findings Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72–207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153–201) in the irradiation group versus 147 days (124–170) in the control group (p=0·0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). Interpretation In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with 125 iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent. Funding National High-tech Research Foundation of China, National Basic Research Program of China, Jiangsu Provincial Special Program of Medical Science, National Scientific and Technical Achievement Translation Foundation, and National Natural Science Foundation of China.

Introduction Mammalian target of rapamycin complex 1 (mTORC1) is an evolutionary conserved multiprotein complex that functions as a key regulator of gene transcription, protein translation, and autophagy. No studies have assessed associations between functional single nucleotide polymorphisms (SNPs) in mTORC1 genes and risk of esophageal squamous cell carcinoma (ESCC). Methods In a case–control study of 1126 ESCC patients and 1131 cancer-free controls, we genotyped eight SNPs in mTORC1 ( mTOR rs1883965 G>A and rs2536 T>C, mLST8 rs3160 C>T and rs26865 G>A, RPTOR rs3751934 C>A, rs1062935 T>C, rs3751932 T>C and rs12602885 G>A) and assessed their associations with risk of ESCC. Results In the single-locus analyses, we found a significantly altered risk of ESCC associated with mTOR rs1883965 A variant genotypes (adjusted OR=1.27 and 1.26; 95% confidence interval=1.01–1.60 and 1.01–1.58 for GA and GA/AA, respectively, compared with GG) but not with other SNPs. In the combined analysis of the eight SNPs, we found individuals with two or more unfavorable genotypes exhibited an increased risk for ESCC (adjusted OR=1.35; 95% confidence interval=1.20–1.62), compared with those with less than two unfavorable genotypes. Such a cumulative effect was dose-dependent ( p trend = 0.004). In the multiple dimension reduction analysis, mTOR rs1883965 was consistently suggested as the strongest individual factor for ESCC risk, and the model including all SNPs yielded the lowest prediction error of 17.66% for model validation. Conclusions These findings suggest that functional SNPs of mTORC1 genes may individually or collectively contribute to ESCC risk. Further validation of these findings is warranted.

XPC polymorphisms may alter DNA repair capacity, thus leading to genetic instability and carcinogenesis. Numerous studies have investigated the associations of XPC Lys939Gln (rs2228001) and Ala499Val (rs2228000) polymorphisms with cancer susceptibility; however, the findings are inconclusive. We searched literature from MEDLINE and EMBASE for eligible publications that assessed the associations between these two polymorphisms and cancer risk. We also assessed genotype-mRNA expression correlation data from HapMap for rs2228001 and rs2228000 in normal cell lines derived from 270 subjects with different ethnicities. The final analysis included 62 published studies of 25,708 cases and 30,432 controls for the Lys939Gln and 34 studies with 14,877 cases and 17,888 controls for the Ala499Val. Overall, Lys939Gln was significantly associated with an increased overall cancer risk (Gln/Gln vs. Lys/Lys: OR = 1.16, 95% CI = 1.07 − 1.25, p

Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome-wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer-free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk. We also used false-positive report probabilities (FPRP) for assessing significant findings. We found that only the rs1883965A variant genotypes were associated with an increased risk of gastric cancer (AG vs. GG: adjusted odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.00–1.59; AA vs. GG: adjusted OR = 1.85, 95% CI = 0.67–5.16 and dominant model: adjusted OR = 1.28, 95% CI = 1.03–1.61). Patients with ≥1 risk genotypes of mTOR had significant increased risk (adjusted OR = 1.25, 95% CI = 1.04–1.49), compared with those having zero risk genotypes. In the stratified analysis, the risk effect of the rs1883965 AG/AA genotypes was evident in subgroups of ever-smokers, non-gastric cardia adenocarcinoma and clinical stage I + II, which were noteworthy findings as evaluated by FPRP. The MDR analysis identified smoking status and rs1883965 as the strongest two-factors for gastric cancer risk. These data support the hypothesis that functional polymorphisms of mTOR may contribute to gastric cancer risk. Clearly, our results require validation in larger studies with different ethnic populations. © 2013 Wiley Periodicals, Inc.

Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is an anti apoptotic and pro-oncogenic signaling molecule involved in the process of immunity, carcinogenesis and tumor progression. Single nucleotide polymorphisms (SNPs) at microRNA-binding sites may change messenger RNA target gene function, thus leading to cancer susceptibility and tumor progression. In this study of 1584 cervical cancer cases and 1394 cancer-free female controls, we investigated associations between three potentially functional SNPs in TNFAIP8 family genes and cervical cancer risk as well as platinum resistance and clinical outcomes in Eastern Chinese women. We found that the TNFAIP8-rs11064 variant GG genotype was associated with an increased risk of cervical cancer compared with AA/AG genotypes (adjusted odds ratio = 2.16, 95% confidence interval = 1.16-4.03, P = 0.015). Further in vitro and ex vivo functional experiments demonstrated that the TNFAIP8-rs11064 variant G allele weakened the binding affinity of miR-22 to the TNFAIP8 3'-untranslated region (UTR) in four cancer cell lines, resulting in increased production of the TNFAIP8 protein in the patients' cervical tissues. In the survival subset, the high TNFAIP8 protein expression was significantly associated with both resistance to cisplatin and nedaplatin, recurrence and death from cervical cancer. Taken together, in the absence of information on human papillomavirus (HPV) infection, the TNFAIP8-rs11064 SNP may function by affecting the affinity of miR-22 binding to the 3'-UTR of TNFAIP8 and regulating TNFAIP8 expression, thus contributing to cervical cancer risk. Additionally, the increased TNFAIP8 protein expression may predict platinum resistance and clinical outcomes in cervical cancer patients. Larger, prospective studies with detailed HPV infection data are warranted to validate our findings.

Background Serine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in the folate metabolic pathway that plays an important role in biosynthesis by providing one carbon unit. SHMT1 C1420T may lead to the abnormal biosynthesis involved in DNA synthesis and methylation, and it may eventually increase cancer susceptibility. Many epidemiologic studies have explored the association between C1420T polymorphism and the risk of non-Hodgkin lymphoma (NHL), but the results have been contradictory. Therefore, we performed this meta-analysis to evaluate the relationship. Methods The meta-analyses were conducted to evaluate the effect of SHMT1 C1420T polymorphism on NHL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. Results Eight studies encompassing 3232 cases and 4077 controls were included. A statistically significant association was found between SHMT1 C1420T polymorphism and NHL risk under the allelic comparison (T vs. C: OR = 1.09, 95% CI 1.01–1.17); a borderline association was found between SHMT1 C1420T polymorphism and NHL risk under the homozygote model (TT vs. CC: OR = 1.18, 95% CI 1.00–1.39) and the dominant model (CT+TT vs. CC: OR = 1.10, 95% CI 1.00–1.21). Conclusion SHMT1 C1420T polymorphism may be associated with NHL risk, which needs to be validated in large, prospective studies.

ERCC2 is indispensable for nucleotide excision repair pathway and its functional polymorphisms may be associated with cancer risk. In a large case-control study of 1126 esophageal squamous cell carcinomas (ESCC) patients and 1131 controls, we genotyped two SNPs in ERCC2 (rs238406 G > T and rs13181 T > G) and assessed their associations with ESCC risk. We found a significantly elevated ESCC risk associated with the rs238406 T variant genotypes (adjusted OR = 1.30 and 1.24, 95% CI = 1.02–1.66 and 1.03–1.49 for TG and TG/TT, respectively, compared with GG), particularly in the subgroup of those smoked more than 16 pack-years. Multivariate logistic regression analysis suggested a possible multiplicative gene-environment interaction between rs238406 genotypes and smoking (Pinteraction = 0.026) on ESCC risk. Although no significant risk associations were observed for rs13181, further mini meta-analysis with our and 18 other published studies of 5,012 cases and 8,238 controls found evidence of an association between the rs13181 variant G allele and esophageal cancer risk (TG/GG vs. TT, OR = 1.17; 95% CI = 1.02–1.33). Interestingly, we consistently found a significant correlation between variant genotypes of these two SNPs and ERCC2 mRNA expression. These findings suggest that potentially functional SNPs in ERCC2 may contribute to ESCC risk.

Affiliations numbers 1 and 3 for multiple authors are incorrect. The correct affiliation number 1 is: Cancer Institute, Fudan University Cancer Center, Shanghai, China. The correct affiliation number 3 is: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

BACKGROUND: Caspase 7 (CASP7) is an important regulator and executioner in the apoptosis pathway and plays a crucial role in cancer development and progression. However, few studies have evaluated associations between functional single nucleotide polymorphisms (SNPs) in the 3' untranslational region (UTR) of CASP7 and risk of gastric cancer. METHODS: In a case-control study of 1117 patients with gastric cancer and 1146 cancer-free controls with frequency matching on age and sex, we genotyped four potentially functional SNPs (rs4353229T>C, rs10787498T>G, rs1127687G>A and rs12247479G>A) located in the microRNA binding sites of the CASP7 3' UTR by using Taqman assays and evaluated their associations with risk of gastric cancer by using logistic regression analyses as well as multifactorial dimension reduction (MDR) analysis. RESULTS: In the single-locus analysis, only the CASP7 rs4353229 TT genotype was associated with 0.83-fold decreased risk (95% confidence interval [CI] = 0.70-0.98) of gastric cancer under a recessive model, compared with the CT/CC genotypes. In the combined analysis of all four SNPs, we found that the risk of gastric cancer decreased by 19% in those carrying any of the risk genotypes (adjusted odds ratio = 0.81, 95% CI = 0.68-0.96), compared with those carrying zero risk genotypes, and this risk was more evident in subgroups of younger age (

BACKGROUND: The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis. CONCLUSIONS/SIGNIFICANCES: In the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13-1.78), P = 0.003 and 1.29 (1.07-1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64-0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04-1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies.

markdownabstract__Background:__ Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations. __Methods:__ We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities. __Results:__ The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity. __Conclusions:__ Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.

Interleukin 6 (IL6) encodes a cytokine protein, which functions in inflammation, maintains immune homeostasis and plays important roles in cervical carcinogenesis. Single nucleotide polymorphisms (SNPs) in IL6 that cause variations in host immune response may contribute to cervical cancer risk. In this two-stage case-control study with a total of 1,584 cervical cancer cases and 1,768 cancer-free female controls, we investigated associations between two IL6 SNPs and cervical cancer risk in Eastern Chinese women. In both Study 1 and Study 2, we found a significant association of the IL6-rs2069837 SNP with an increased risk of cervical cancer as well as in their combined data (OR 1.27 and 1.19, 95% CI 1.08-1.49 and 1.04-1.36, P = 0.004 and 0.014 for dominant and additive genetic models, respectively). Furthermore, rs2069837 variant AG/GG carriers showed significantly higher levels of IL6 protein than did rs2069837 AA carriers in the target tissues. Using multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses, we observed some evidence of interactions of the IL6 rs2069837 SNP with age at primiparity and menopausal status in cervical cancer risk. We concluded that the IL6-rs2069837 SNP may be a marker for susceptibility to cervical cancer in Eastern Chinese women by a possible mechanism of altering the IL6 protein expression. Although lacked information on human papillomavirus (HPV) infection, our study also suggested possible interactions between IL6 genotypes and age at primiparity or menopausal status in cervical carcinogenesis. However, larger, independent studies with detailed HPV infection data are warranted to validate our findings.

BACKGROUND: Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair; its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus contribute to cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: In a hospital-based case-control study of 1115 esophageal squamous cell carcinoma (ESCC) cases and 1117 cancer-free controls, we genotyped three potentially functional SNPs of ERCC5 (SNPs, rs2296147T>C, rs2094258C>T and rs873601G>A) and estimated crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for their associations with risk of ESCC using unconditional logistic regression models. We also calculated false-positive report probabilities (FPRPs) for significant findings. We found that compared with the TT genotype, ERCC5 rs2296147 C variant genotypes were associated with a significantly lower ESCC risk (CT: adjusted OR = 0.76, 95% CI = 0.63-0.93, CT/CC: adjusted OR = 0.80, 95% CI = 0.67-0.96); however, this risk was not observed for the other two SNPs (rs2094258C>T and rs873601 G>A), nor in further stratification and haplotype analysis. CONCLUSIONS/SIGNIFICANCES: These findings suggested that ERCC5 polymorphisms may contribute to risk of ESCC in Eastern Chinese populations, but the effect was weak and needs further validation by larger population-based case-control studies.

Background Xeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive. Methodology/Principal Findings In this meta-analysis of 47,639 cancer cases and 51,915 controls, by searching three electronic databases (i.e., MEDLINE, EMBASE and CNKI), we summarized 43 case-control studies from 29 publications on four commonly studied polymorphisms of XPF (i.e., rs1800067, rs1799801, rs2020955 and rs744154), and we did not find statistical evidence of any significant association with overall cancer risk. However, in stratification analyses, we found a significant association of XPF-rs1799801 with a reduced cancer risk in Caucasian populations (4,845 cases and 5,556 controls; recessive model: OR = 0.87, 95% CI = 0.76–1.00, P = 0.049, P = 0.723 for heterogeneity test, I2 = 0). Further genotype-phenotype correlation analysis showed that the homozygous variant CC genotype carriers had higher XPF expression levels than that of the TT genotype carriers (Student’s t test for a recessive model: P = 0.046). No publication bias was found by using the funnel plot and Egger’s test. Conclusion This meta-analysis suggests a lack of statistical evidence for the association between the four XPF SNPs and overall risk of cancers. However, XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies.

Background mTOR is an important intracellular mediator involved in the PI3K/AKT signalling pathway and a critical regulator of cell growth and proliferation in response to environmental and nutritional conditions. We evaluated potentially functional polymorphisms in the 5′ untranslated region (UTR) of the mTOR gene associated with the risk of gastric cancer. Methods In this case–control study with 1123 patients and 1113 healthy controls matched for age and gender, we genotyped four potentially functional single nucleotide polymorphisms (SNPs) located in 5′ UTR of the mTOR gene and evaluated their association with risk of gastric cancer. Findings In individual polymorphism analysis, the rs1034528 G > C was associated with 1.21-times increased risk of gastric cancer under a dominant model (adjusted odds ratio 1.21, 95% confidence interval [CI] 1.01–1.46). When the four polymorphisms were combined, the risk of gastric cancer increased in a dose-dependent manner as the number of risk genotypes increased (ptrend = 0.001). Patients with three or four risk genotypes had a significantly higher risk of gastric cancer than those with 0–2 risk genotypes (adjusted odds ratio 1.41, 95% CI 1.15–1.73). Stratification analysis indicated that the combined effect of risk genotypes was more evident in subgroups of older age (>59 years), men, smokers, non-drinkers, patients with gastric cardia adenocarcinoma, and those with clinical stage III and IV disease. Further analysis using mRNA expression data from the HapMap project suggested that both CG and CC carriers of rs1034528 G > C were associated with non-significantly decreased expression of mTOR mRNA in normal cell lines from 45 Chinese patients (p = 0.97 for CG carriers, p = 0.38 for CC carriers). Interpretation Functional mTOR variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate these findings.

Background MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma. Methods In this case–control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women. Results We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma. Conclusions The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.