Association of IL-10 polymorphisms with prostate cancer risk and grade of disease

Animal and in vitro models of prostate cancer demonstrate high IL-10 levels result in smaller tumors, fewer metastases, and reduced angiogenesis compared to controls. We sought to examine the hypothesis that genotypes correlated with low IL-10 production may be associated with increased prostate cancer risk among Finnish male participants from the Alpha-tocopherol Beta-carotene Cancer Prevention Study. DNA from 584 prostate cancer cases and 584 controls was genotyped for four IL-10 alleles, −1082, −819, −592, and 210. DNA from more of the controls than cases failed to amplify, resulting in 509 cases and 382 controls with genotype data for −1082; 507 and 384 for −819; 511 and 386 for −592; and 491 and 362 for 210. Odds ratios for the association between the IL-10 genotypes and risk of prostate cancer or, among cases only, high-grade disease were calculated using logistic regression. In this population, the −819 TT and −592 AA low expression genotypes were highly correlated. These two genotypes also were associated with increased prostate cancer susceptibility (OR = 1.92, 95% CI 1.07–3.43 for −819) and, among cases, with high-grade tumors (OR = 2.56, 95% CI 1.26–5.20 for −819). These data demonstrate genotypes correlated with low IL-10 production are associated with increased risk of prostate cancer and with high-grade disease in this population. The U.S. Government’s right to retain a non-exclusive, royalty-free license in and to any copyright is acknowledged.     

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。     

Association of IL-10 rs1800871 and rs1800872 Polymorphisms with Breast Cancer Risk: A Systematic Review and Meta-Analysis

Background: The rs1800871 and rs1800872 polymorphisms of interleukin 10 (IL-10) gene has been indicated tobe associated with breast cancer (BC) risk, but study results are still debatable. To derive a more precise evaluation, weperformed a comprehensive meta-analysis. Methods: Multiple electronic databases were searched to identify studiesassessing the IL-10 rs1800871 and rs1800872 polymorphisms with BC risk. Results: A total of 21 case-control studieswith 6054 cases and 6355 controls were included in this met-analysis. There was a significant association between thers1800871 polymorphism and BC risk (CT vs. TT: OR= 1.17, 95% CI 1.01-1.35, p=0.02; and CC+CT vs. TT: OR= 1.29,95% CI 1.00-1.66, p=0.04). Moreover, increased BC risks were also associated with the rs1800872 polymorphism (Cvs. A: OR= 1.29, 95% CI 1.04-1.60, p=0.01; CC vs. AA: OR= 1.54, 95% CI 1.03-2.30, p=0.03; CC+CA vs. AA: OR=1.43, 95% CI 1.01-2.01, p=0.03; and CC vs. CA+AA: OR= 1.23, 95% CI 1.01-1.51, p=0.04). A pooling of the studieswas also conducted by ethnicity, but failed to show an association of IL-10 rs1800871 and rs1800872 polymorphismwith BC risk in Asians and Caucasians. Conclusions: Our results are inconsistent with previous meta-analysis suggeststhat IL-10 rs1800871 and rs1800872 polymorphisms might contribute to BC susceptibility in overall population, butnot by ethnicity.     

Quantitative assessment of the influence of EPHX1 gene polymorphisms and cancer risk: a meta-analysis with 94,213 subjects

Purpose

Previous studies investigating the association between EPHX1 polymorphisms (Tyr113His and His139Arg) and cancer risk have yielded inconsistent results. This meta-analysis was performed to derive a more precise estimation of relationship between two EPHX1 polymorphisms and risk of different types of cancer.

Methods

Data were extracted from relevant studies detected by a systematic literature search. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association between EPHX1 polymorphisms and cancer risk.

Results

This meta-analysis carefully collected 99 studies on these two polymorphisms and cancer risk published up to March 2014, consisting of 45 studies (20,091 cases and 27,396 controls) for Tyr113His and 54 studies (19,437 cases and 27,289 controls) for His139Arg. The results in overall population did not show any significant association between these two polymorphisms and cancer risk for all genetic models. However, EPHX1 Tyr113His homozygote individuals have a significantly increased risk of cancer among Asians (homozygote model: OR =1.46, 95% CI=1.05–2.03; recessive model: OR =1.39, 95% CI =1.10–1.76) and mixed population (homozygote model: OR =1.17, 95% CI =1.02–1.34; recessive model: OR =1.17, 95% CI =1.02–1.33), but not Caucasians.

Conclusion

His/His genotype of EPHX1 Tyr113His polymorphism is a risk factor for developing caner for Asian and mixed population, while no evidence was found for the association between the EPHX1 His139Arg polymorphism and increased cancer risk.

Electronic supplementary material

The online version of this article (doi:10.1186/s13046-014-0082-9) contains supplementary material, which is available to authorized users.     

Lack of association between the 8-oxoguanine DNA glycosylase gene Ser326Cys polymorphism and gastric cancer: evidence from a meta-analysis

Objective: To evaluate the association of 8-oxoguanine DNA glycosylase gene (OGG1) Ser326Cys polymorphism with gastric cancer via a comprehensive meta-analysis. Methods: A total of 12 publications were identified before January 20, 2011 including 1,390 cases and 3,299 controls. A random-effects model was applied irrespective of between-study heterogeneity. Data and study quality were assessed in duplicate. Results: No significant association was found for either allele or genotype with gastric cancer (odds ratio [OR]=0.96; 95% confidence interval [95% CI]: 0.82–1.13; P=0.66), and this was also the case after combining 326Ser/Cys and 326Ser/Ser genotypes together (OR=0.87; 95% CI: 0.63–1.20; P=0.40), or 326Cys/Cys and 326Ser/Cys together (OR=1.03; 95% CI: 0.87–1.22; P=0.72). Subgroup analysis by ethnicity indicated that comparison of allele 326Ser versus 326Cys generated a weakly and non-significantl protective effect on gastric cancer in Asians (OR=0.90; 95% CI: 0.75–1.09; P=0.29) and Turks (OR=0.65; 95% CI: 0.37–1.14; P=0.13), but a non-significant risk effect in Europeans (OR=1.10; 95% CI: 0.78–1.54; P=0.60) and Brazilians (OR=1.13; 95% CI: 0.81–1.58; P=0.48). No publication bias was observed. Conclusions: Our results collectively suggest that the OGG1 Ser326Cys polymorphism might not be a potential candidate risk factor for the development of gastric cancer.     

The RAD51 gene family, genetic instability and cancer

Prostate cancer (CaP) is the most commonly diagnosed nonskin cancer and the second leading cause of cancer death in American men. Its etiology is not fully understood. Ethnicity/race and family history are associated with it, and incidence increases with age. As with other solid tumors, accumulation of mutations and decline in DNA repair during aging may lead to CaP. However, we believe that conducting a large population screening for every cancer susceptibility gene (e.g. DNA repair) is only meaningful, if we can predict to what extent genetic variants contribute to DNA-repair functional phenotype and CaP risk. This review focuses on the association between CaP and nucleotide excision repair (NER), because some of the DNA adducts generated by CaP-related carcinogens are removed by the NER pathway, and our previous data showed a significant association between lower NER capacity (NERC) and CaP risk. Many laboratories, including ours, have employed a variety of approaches to evaluate the functional significance of DNA-repair single-nucleotide polymorphisms (SNPs) in human cancer risk assessment. Genetic profiling and computational modeling that can predict NERC may have great potential for CaP-risk assessment, because the current NERC assay is quite labor intensive, costly, and therefore not suitable for population-based screening.     

Single nucleotide polymorphisms and haplotypes in the gene for vascular endothelial growth factor and risk of prostate cancer

Vascular endothelial growth factor (VEGF) plays a key role in the regulation of angiogenesis and has been related to cancer development and progression. To evaluate the role of VEGF single nucleotide polymorphisms (SNPs) and haplotypes in prostate cancer, we performed a case–control study including 702 prostate cancer patients and 702 male age-matched healthy control subjects. Seven VEGF candidate polymorphisms were determined by 5′-nuclease (TaqMan) assays. Furthermore, VEGF plasma levels and genotypes were analysed in a group of 64 healthy men. Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms upstream of the coding sequence (promoter and 5′-untranslated region) and two polymorphisms downstream of the coding sequence. None of the single polymorphisms or haplotypes was significantly associated with the presence of prostate cancer. In a multivariate regression analysis including age, VEGF genotypes and haplotypes as covariates and VEGF plasma level as dependent variable, none of the VEGF polymorphism or haplotypes was a significant predictor of VEGF plasma levels. The present data suggest that polymorphisms or haplotypes in the VEGF gene do not modify the risk of prostate cancer.     

Genetic variability of the fatty acid synthase pathway is not associated with prostate cancer risk in the European Prospective Investigation on Cancer (EPIC)

A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk.     

Age-specific association of steroid hormone pathway gene polymorphisms with breast cancer risk

BACKGROUND: Breast cancer (BC) is a complex disease, and the incidence rates for BC increase with age. Both environmental factors and genetics have an impact on the risk of BC. Although the effects of environmental factors may vary with age, it has been assumed generally that the penetrance of single nucleotide polymorphisms (SNPs) is constant throughout life. In the current study, the results demonstrated that certain SNPs exhibit BC risk associations that vary considerably with age. METHODS: SNPs in 12 steroid hormone pathway genes were investigated for associations with BC risk in white women who were enrolled in an age-matched, case-control (1:2 for cases and controls, respectively) study that consisted of a discovery set (n = 5000 women) and an independent validation set (n = 1583 women). RESULTS: Significant age-related trends were identified and confirmed for SNPs in 4 genes associated with BC risk. The cytosine/cytosine (C/C) genotype of cytochrome P450 XIB2 (CYP11B2) was associated with decreased risk at younger ages (ages 30-44 years) but an increased risk at older ages (ages 55-69 years). The homozygous cytosine-guanine (CG/CG) genotype of uridine phosphorylase glycosyltransferase 1A7 (UGT1A7) was associated with increased risk at younger ages but decreased risk at older ages. Associations in cytochrome P450 19 (CYP19) and progesterone receptor (PGR) were confined to middle age (ages 45-54 years). CONCLUSIONS: The identification of age-specific genetic associations may have profound implications for future etiologic studies of BC and for the use of SNP genotyping to accurately predict the risk of BC in women.     

Genetic association of cytokine DNA polymorphisms with head and neck cancer

Mutations in oncogenes or tumor suppressor genes, as well as environmental factors such as tobacco chewing or smoking, poor oral hygiene, ill-fitting dental appliances, infection by certain HPV types, or alcohol abuse, seem to be involved in the multifactorial process of carcinogenesis in head and neck. Recently, several genetic association studies have indicated that common DNA polymorphisms in low penetrance genes may affect the susceptibility of an individual to malignancy. Cytokines are an important group of proteins that regulate and mediate inflammation and angiogenesis. Tumor growth, invasion and metastasis are facilitated when there is a deregulation in their production. Cytokines include interleukins (ILs), tumor necrosis factors (TNFs) and certain growth factors (GFs). A number of genetic association studies have recently investigated the putative correlation between functional DNA polymorphisms in cytokine genes and head and neck carcinomas. This review discusses the findings of such studies in oral, nasopharyngeal and esophageal squamous cell carcinomas. Extensive research has indicated that functional polymorphisms affecting gene expression of IL-4,-6,-8,-10 as well as TNF-α are strongly associated with increased risk for oral cancer. Gene expression of TNF-α seems to be associated also with esophageal carcinomas, while for nasopharyngeal cancer the picture is yet unclear. It is generally believed that such genetic association studies will gradually increase our knowledge regarding the predisposed manifestation and advancement of these malignancies in the head and neck region.     

MTHFR polymorphisms and pancreatic cancer risk: lack of evidence from a meta-analysis

Objective: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported tobe associated with pancreatic cancer, but the published studies had yielded inconsistent results.We thereforeperformed the present meta-analysis. Methods: A search of Google scholar, PubMed, Cochrane Library andCNKI databases before April 2012 was conducted to summarize associations of MTHFR polymorphisms withpancreatic cancer risk. Assessment was with odds ratios (ORs) and 95% confidence intervals (CIs). Publicationbias were also calculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C)were involved in this meta-analysis. Overall, C667T(TT vs. CC : OR = 1.61, 95%CI = 0.78 - 3.34; TT vs. CT :OR = 1.41, 95%CI = 0.88-2.25; dominant model: OR = 0.68, 95%CI = 0.40-1.17; recessive model: OR = 0.82,95%CI = 0.52-1.30) and A1298C(CC vs. AA:OR=1.01, 95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14;dominant model: OR=1.01, 95%CI = 0.47-2.20; recessive model: OR = 1.01, 95%CI = 0.80-1.26) did not increasepancreatic cancer risk. Conclusion: This meta-analysis indicated that MTHFR polymorphisms (C667T andA1298C) were not associated with pancreatic cancer risk.     

BRCA1 and VDR gene polymorphisms are associated with prostate cancer risk in Mexican men

Prostate cancer (PC) is a polygenic disease with broad differences across ethnicities. BRCA1/2 and VDR have exhibited a featured genetic contribution to PC development in European populations. Nonetheless, its contribution in Latino populations specifically among Mexican men, where 70% of PC cases are detected in advanced stages, is still unknown. The contribution of seven polymorphisms in BRCA1/2 and VDR genes to PC susceptibility was evaluated in 370 incident PC cases and 759 age-matched (±5 years) controls belonging to the Mexican population. Based on Gleason score at diagnosis, PC cases were classified as well-differentiated PC (Gleason <7) and moderate or poorly differentiated PC (Gleason ≥7). Age at diagnosis was used to divided PC cases in earlier (<60 years) and late-onset PC (≥60 years). Prostate and breast cancer family histories were obtained through interview. Our results provided evidences about the contribution of BRCA1-rs1799966 (OR_{CC genotype} = 2.30; 95% confidence interval [CI] = 1.36-3.91) to the moderate or poorly differentiated PC risk, independently of the family history of prostate, breast or ovary cancer. Further, VDR-rs2238135-G allele was associated with early-onset PC (OR_{G allele} = 2.05; 95% CI = 1.06-3.95), and marginally with moderate or poorly differentiated PC risk. The present study revealed the crucial role of BRCA1 in PC aggressiveness risk, outstanding the gender imbalance regarding the breast cancer risk in women.     

Lack of radiation dose response for patients with low-risk clinically localized prostate cancer: a retrospective analysis

The need for dose escalation for patients with low-risk clinically localized prostate cancer remains controversial. In this study, we report our pooled institutional experience of low-risk patients treated with a range of “standard” radiation doses to assess outcome in regard to biochemical failure and to determine whether a dose-response relationship exists within this conventional dose range.

Patients with low-risk clinically localized prostate cancer (T1 or T2a, Gleason grade ≤6, and prostate-specific antigen ≤10 ng/mL) treated at Joint Center for Radiation Therapy-affiliated institutions between October 1989 and September 1997 were retrospectively analyzed for freedom from biochemical failure. The dose was prescribed volumetrically with 95% normalization to between 5760 and 6900 cGy (6100 and 7300 cGy ICRU reference point dose). Patients were stratified into 3 groups with relatively equal numbers of patients (<6660, 6660, and >6660 cGy). To ensure that any differences in biochemical failure between patients at the lower and higher ends of the dose range used were not masked by analysis of the entire cohort, patients receiving ≤6500 cGy or ≥6800 cGy were subsequently analyzed separately. Biochemical failure was defined per the ASTRO consensus definition. The log-rank test was used to assess for differences in follow-up and time to biochemical failure. A Kaplan-Meier plot of time to biochemical failure for the initial 3 subgroups was generated.

A total of 264 patients were identified. Sixteen patients whose dose was not recorded in the database were excluded from analysis. The median follow-up was 35 months. No significant differences were found in baseline prostate-specific antigen, Gleason grade, or clinical stage among the groups. The overall actuarial rate of 5-year freedom from biochemical failure was 80.2%. By dose level, the 5-year biochemical failure-free rate was 79.2%, 78.4%, and 84.5% for <6660 cGy, 6660 cGy, and >6660 cGy, respectively. These differences were not significant. Subsequently, 45 patients receiving ≤6500 cGy were compared with 23 patients receiving ≥6800 cGy. The difference between these groups was not significant. The 5-year freedom from biochemical failure rate for the patients receiving ≤6500 cGy was 89.9%.

Within a range of doses considered standard for treatment of low-risk clinically localized prostate cancer during an 8-year period, no improvement in biochemical freedom from failure was noted with the higher doses. The overall 5-year rate of freedom from biochemical failure is consistent with that reported by others with standard and escalated external beam doses used in this low-risk population. A prospective randomized study is necessary to define the optimal dose in this patient population.     

Cancer of the uterine cervix may be significantly associated with a gene polymorphism coding for increased IL-10 production.

The purpose of our prospective, case-controlled study was to investigate the hypothesis that women who are genetically programmed to produce high or medium levels of IL-10 were more likely to develop cancer of the uterine cervix than individuals genetically predisposed to low IL-10 production. The population was recruited from patients attending gynecological clinics at 2 hospitals in Harare, Zimbabwe. Laboratory tests were performed in the Departments of Immunology, Chemical Pathology and Medical Microbiology, Medical School, University of Zimbabwe, and simultaneously at the Department of Biological Sciences, University of Manchester, United Kingdom. Included in our study were 77 women with histologically proven cancer of the uterine cervix and 69 age- and parity-matched healthy women. All of the patients and healthy controls were from the Shona ethnic group that inhabits northern Zimbabwe. DNA was purified from cervical cytobrush samples obtained from women with cervical cancer. Control DNA was extracted from urine or peripheral blood samples from the healthy women. The Qiagen DNA extraction kit was used. Detection of allele A and/or G at -1082 in the promoter region of the IL-10 gene was carried out using the ARMS-PCR technique. Polymorphism in the amplified products was detected by gel electrophoresis in the presence of ethidium bromide and were bands visualized under UV light. The data comprise 77 women who developed invasive cervical cancer and 69 healthy women matched for age and parity. Patients with cancer were significantly (p = 0.001) more likely to be predisposed to produce higher (A/G) levels of IL-10. The genotype encoding for high (G/G) production of IL-10 was only observed in one cancer patient. The prevalence of low producers of IL-10 in the cancer group was significantly lower than in the healthy women. There were no high producers amongst the healthy women. These data suggest that the genetically acquired ability to produce higher levels of IL-10 may be a significant factor in the development of cervical cancer.     

Fine mapping of 11q13.5 identifies regions associated with prostate cancer and prostate cancer death

BackgroundChromosomal region 11q13–14 associates with prostate cancer (PrCa). Previously, we identified a rare intronic mutation on EMSY (11q13.5) that increases the risk of aggressive PrCa and associates with familial PrCa. Here, we further study the genetic structure and variants of the PrCa susceptibility region 11q13.5.MethodsThis study included 2716 unselected hospital-based PrCa cases, 1318 cases of a screening trial and 908 controls of Finnish origin. We imputed single nucleotide polymorphisms (SNPs) and structural variants from the 1000 Genomes Project and validated the associations of the variants in two PrCa patient sets by genotyping. Genetic structure was studied with haplotype analysis.ResultsTwo independent regions at 11q13.5 were associated with PrCa risk. The most significant association was at EMSY (rs10899221, odds ratio (OR) 1.29–1.40, P = 3.5 × 10^?4–0.002) near the previously identified mutation. Correlated intronic SNPs rs10899221 and rs72944758 formed with other EMSY variants common and rare haplotypes that were associated with increased risk (P = 4.0 × 10^?4) and decreased risk (P = 0.01) of PrCa, respectively. The other associated region was intergenic. Among the six validated variants, rs12277366 was significant in both patient sets (OR 1.15–1.17, P = 0.01). Haplotypes associated with an increased risk (P = 0.02) and a decreased risk (P = 0.02) were identified. In addition, the intergenic region was strongly associated with PrCa death, with the most significant association at rs12277366 (OR = 0.72, P = 4.8 × 10^?5).ConclusionsThese findings indicate that 11q13.5 contributes to PrCa predisposition with complex genetic structure and is associated with PrCa death.     

Lack of association between vitamin D receptor gene FokI and BsmI polymorphisms and prostate cancer risk: an updated meta-analysis involving 21,756 subjects

The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. The polymorphisms in the VDR gene have been hypothesized to alter the risk of prostate cancer. However, studies investigating the association between VDR polymorphisms (BsmI and FokI) and prostate cancer (PCa) risk report conflicting results , therefore, we conducted a meta-analysis to re-examine the controversy. Published literatures from PubMed, Embase, Google Scholar, and China National Knowledge Infrastructure (CNKI) were searched (updated to March 9, 2013). According to our inclusion criteria, studies that observed the association between VDR BsmI and FokI polymorphisms and PCa risk were included. The principal outcome measure was the odds ratio (OR) with 95 % confidence interval (CI) for PCa risk associated with VDR BsmI and FokI polymorphisms. Thirty-four studies involving 10,267 cases and 11,489 controls were recruited. Overall, we did not find evidence to support an association between any of the VDR polymorphisms and PCa risk. For BsmI, the pooled OR was 0.894 (95 % CI 0.773 to 1.034) for the Bb vs. bb genotypes, 1.002 (95 % CI 0.869 to 1.157) for the BB vs. bb genotypes, 0.922 (95 % CI 0.798 to 1.065) for the dominant model (BB/Bb vs. bb), and 1.018 (95 % CI 0.936 to 1.107) for the recessive model (BB vs. Bb/bb). ORs for the FokI polymorphisms were similar. The results suggest that the VDR BsmI and FokI polymorphisms are not related to PCa risk. Further large and well-designed studies are required to confirm this conclusion.     

Integrated models for the prediction of late genitourinary complaints after high-dose intensity modulated radiotherapy for prostate cancer: Making informed decisions

Background and purpose

To develop predictive models for late radiation-induced hematuria and nocturia allowing a patient individualized estimation of pre-treatment risk.

Materials and methods

We studied 262 PCa patients treated with curative intensity modulated radiotherapy to the intact prostate or prostate bed. A total of 372 variables were used for prediction modeling, among which 343 genetic variations. Toxicity was scored using an in-house developed toxicity scale. Predictor selection is achieved by the EMLasso procedure, a penalized logistic regression method with an EM algorithm handling missing data and crossvalidation avoiding overfit. Model performance was expressed by the area under the curve (AUC) and by sensitivity and specificity.

Results

Variables of the model predicting late hematuria (36/262) are bladder volume receiving ?75 Gy, prostatic transurethral resection and four polymorphisms. (AUC = 0.80, sensitivity = 83.3%, specificity = 61.5%). The AUC drops to 0.67 when the genetic markers are left out. The model that predicts for late nocturia (29/262) contains the minimal clinical target volume (CTV) dose, the CTV volume and three polymorphisms (AUC = 0.76, sensitivity = 75.9%, specify = 67.4%). This model is a better predictor for nocturia compared to the nongenetic model (AUC of 0.60).

Conclusions

We were able to develop models that predict for the occurrence of late radiation-induced hematuria and nocturia, including genetic factors which might improve the prediction of late urinary toxicity.     

Association of Promoter Region Polymorphisms of IL-10 Gene with Susceptibility to Lung Cancer: Systematic Review and Meta-Analysis

Objective: Epidemiological studies have suggested that the promoter region polymorphisms of interleukin-10 (IL-10)gene may be associated with an increased risk of lung cancer. However, those studies results are controversial. Thus, acomprehensive meta-analysis was performed to evaluate the association of promoter region polymorphisms of IL-10gene with susceptibility to lung cancer. Methods: a comprehensive search of PubMed, EMBASE, and CNKI databaseswas performed to find all eligible studies up to September 15, 2018. The pooled odds ratios (ORs) with 95% confidenceintervals (CIs) were used to assess the strength of such association. Results: A total number of 19 case-control studies with4084 cases and 6,131 controls were selected. The overall meta-analysis results showed that the -592A>C polymorphismwas significantly associated with lung cancer risk under four genetic models, i.e., allele (CT vs. TT: OR= 1.17, 95% CI1.01-1.35, p=0.02), homozygote (CC vs. AA: OR= 1.64, 95% CI 1.29-2.02, p≤0.001), heterozygote (CA vs. AA: OR=1.26, 95% CI 1.06-1.50, p≤0.001), and dominant (CC+CA vs. AA: OR= 1.31, 95% CI 1.11-1.54, p=0.001). However,there was no significant association between -819T>C and -1082A>G polymorphisms of IL-10 and lung cancer risk.Similarly, subgroup analyses by ethnicity detected significant association between IL-10 -592A>C and lung canceramong Asians and Caucasians. Conclusions: Our meta-analysis suggests that the IL-10 -592A>C polymorphism mightbe risk factor for lung cancer, especially among Asian and Caucasians. In contrast, the IL-10 -819T>C and -1082A>Gpolymorphisms are not significantly associated with increased risk of lung cancer.