Genetic polymorphism and immune response to tuberculosis in indigenous populations: a brief review

We systematically reviewed studies of the immune response to tuberculosis and the genetic polymorphisms associated with Th1- or Th2-mediated cytokine expression in indigenous populations. A bibliographic search was performed on the Medline and ISI databases and included studies published between January 1980 and October 2011. The search terms were tuberculosis, American Indians, Amerindian, indigenous, Indians, native people, aboriginal, immun*, host immune, immune response, cytokine*, polymorphism*, and gene. Regardless of their design, studies that evaluated immunoglobulin, cytokine levels and genetic polymorphisms that altered cytokine expression were included. Thirteen studies met the inclusion criteria. The majority of studies were performed in Latin America, and five investigated the Warao ethnic group of Venezuela. Most of the investigations indirectly evaluated the immune response. Higher anergy to the tuberculin skin test, higher IgG4 and IgM levels, higher IL-5 production and lower TNF-α, IL-12p40 and IFN-γ production were found in the indigenous populations. The studies also reported a predominantly Th2-type response in these populations and a possibly higher susceptibility to tuberculosis. A better understanding of the relevant genetic polymorphisms and their role in immune regulation would help to clarify the immunogenetic mechanisms of TB infection in these populations. This information would be useful for identifying new treatments and preventing infection and progression to active disease.     

Ethnic differences in gastric cancer genetic susceptibility:Allele flips of interleukin gene

Polymorphisms in promoter regions of inflammatory cytokines have been widely studied,and potentially functional polymorphisms have been discovered.Conflicting results from meta-analyses of interleukin(IL)-1B and IL-10 polymorphisms show differences in gastric cancer susceptibilities between Caucasian and Asian populations.In particular,we note the suggestion of an allele flip in IL-1B and IL-10 gene polymorphisms.In Asian populations,the IL-1B-1464G/-511C/-31T haplotype indicates risk for gastric cancer,while the opposite haplotype,IL-1B-1464C/-511T/-31C is the risk-related allele in Caucasians.Furthermore,while IL-10-1082G/-819C/-592C is associated with gastric cancer in Asians,IL-10-1082A/-819T/-592T is linked to gastric cancer risk in Caucasians.These seemingly contradictory results may be attributed to distinct carcinogenic mechanisms underlying the different gastric cancer subtypes.The allele flip observed in IL-10 and gastric cancer appears to reflect allelic heterogeneity,similar to that observed in IL-1B.In this review,we focus on the allele flip phenomenon observed between different ethnic groups in an effort to resolve certain controversial results from recent studies on interleukin polymorphism.In addition,we re-emphasize the importance of stratifying gastric cancer subtypes based on anatomical site and Lauren classification to prevent false associations arising through dilution of true ones.     

Gene-diet interactions in gastric cancer risk: A systematic review

AIM: To conduct a systematic review of the published epidemiological studies investigating the association of the interactions between gene variants and dietary intake with gastric cancer risk.METHODS: A literature search was conducted in PubMed, EMBASE, and MEDLINE for articles published between January 2000 and July 2013, and 38 studies were identified. Previous studies included various dietary factors (e.g., fruits and vegetables, soybean products, salt, meat, and alcohol) and genetic variants that are involved in various metabolic pathways.RESULTS: Studies suggest that individuals who carry high-risk genetic variants and demonstrate particular dietary habits may have an increased risk of gastric cancer compared with those who do not carry high-risk genetic variants. Distinctive dietary patterns and variations in the frequency of genetic variants may explain the higher incidence of gastric cancer in a particular region. However, most previous studies have limitations, such as a small sample size and a retrospective case-control design. In addition, past studies have been unable to elucidate the specific mechanism in gene-diet interaction associated with gastric carcinogenesis.CONCLUSION: Additional large prospective epidemiological and experimental studies are required to identify the gene-diet metabolic pathways related to gastric cancer susceptibility.     

Association of IL-17 polymorphisms with gastric cancer risk in Asian populations

AIM: To investigate associations between the IL-17 rs2275913 GA and rs763780 TC polymorphisms and susceptibility to gastric cancer in Asian populations. METHODS: We reviewed studies published up to 2014 on IL-17 polymorphisms with gastric cancer susceptibility systematically. Relevant articles were identified in the MEDLINE, Science Citation Index, Cochrane Library, Pub Med, EMBASE, CINAHL and Current Contents Index databases. We used version 12.0 STATA statistical software to evaluate the statistical data. Two reviewers abstracted the data independently. Odds ratios(ORs) and 95% confidence intervals(95%CIs) were calculated. RESULTS: Seven independent, case-control studies were chosen for the meta-analysis, which included 3210 gastric cancer patients and 3889 healthy controls. The overall estimation showed a positive association between the IL-17 rs2275913 GA polymorphism and the occurrence of gastric cancer for five genetic models(all P 0.05) and similar results were observed for the IL-17 rs763780 TC variation with four genetic models(all P 0.05), but not for the dominant model(P 0.05). Subgroup analysis by country revealed that the rs2275913 GA and rs763780 TC polymorphisms may be the main risk factor for gastric cancer in Chinese and Japanese populations. CONCLUSION: The IL-17 gene may be significantly correlated with gastric cancer risk in Asian populations, especially those carrying the rs2275913 GA and rs763780 TC polymorphisms.     

Preliminary analysis of single-nucleotide polymorphisms in IL-10, IL-4, and IL-4Rα genes and profile of circulating cytokines in patients with gastric Cancer

Background

Gastric Cancer is highly prevalent and deadly worldwide. In Colombia, it is the most lethal form of cancer. Some single-nucleotide polymorphisms in IL-10, IL-4, and IL-4Rα genes have been associated with an anti-inflammatory environment and a Th2 profile in detriment of the antitumor Th1 response. This research sought to detect single-nucleotide polymorphisms in promoter sequences, like ??1082 (G/A), ??592 (C/A), and???819 (C/T), as well as ??590 (C/T) of the IL-10 and IL-4 genes, respectively; in addition to the IL-4Rα mutation variants, Ile50Val and Q576R, together with circulating levels of IL-4, TNF-α, IL-10, and IFN-γ in patients with gastric carcinoma in Cúcuta, Colombia.

Methods

In a cross-sectional study, 17 patients and 30 healthy individuals were genotyped for the six polymorphisms mentioned through PCR-RFLP of DNA obtained from peripheral blood cells and serum samples were analyzed by sandwich ELISA to quantify cytokines. Statistical difference between groups was determined along with the association between the presence of polymorphisms and the risk of gastric cancer, as well as the mortality in patients, using Mann-Whitney U test and logistic regression analysis, respectively.

Results

An association between the ??1082 (G/A) and the risk of gastric cancer was found (OR?=?7.58, range 0.77–74.06, P?=?0.08). Furthermore, patients had a significant increase in IL-4 serum levels (P?<?0.01) compared to healthy individuals, both variables showed a higher estimated risk of mortality in patients, although without statistical association (P?>?0.05).

Conclusion

We infer that two possible biomarkers (one immunological and one genetic) could be considered in association with gastric cancer in our population, which should be confirmed by subsequent studies involving a greater number of individuals.

     

A candidate gene approach of immune mediators effecting the susceptibility to and severity of upper gastrointestinal tract diseases in relation to Helicobacter pylori and Epstein-Barr virus infections

This review focuses on immunogenetic aspects of diseases of the upper gastrointestinal tract in which infectious agents may play a role in the aetiopathogenesis, such as Helicobacter pylori, Epstein-Barr virus (EBV) and HIV. Gastric adenocarcinoma is a common cancer all around the world, with declining incidences in Europe and high incidences in Asia and central and south America. Together with gastric atrophy and peptic ulcer disease, gastric adenocarcinoma belongs to the commonest upper gastrointestinal tract diseases. These diseases are multifactorial and factors such as smoking and dietary habits contribute to the pathogenesis. More recently, scientists have turned their eyes on the host. Functional polymorphisms in the genes regulating the host immune system may contribute to the susceptibility to and progression of disease. In multifactorial and polygenetic diseases, candidate gene studies of single nucleotide polymorphisms (SNPs) detect small to moderate relative risks. Unfortunately, only a few functional SNPs have been identified. The candidate gene approach can be seen as a useful first step in exploring causal pathways between genetic determinants and complex diseases such as those mentioned above. To date, little is known about the immunogenetics of upper gastrointestinal tract diseases. We review the literature on H. pylori, EBV and gene polymorphisms that affect key immune mediators influencing the pathogenesis of the inflammatory response, such as the genes that code for the IL-1 family, TNF-alpha, lymphotoxin alpha, and IL-10. IL-1, IL-10, lymphotoxin alpha and TNF-alpha polymorphisms increase the risk of upper gastrointestinal pathogenesis in H. pylori-infected patients, whereas IL-1 and TNF-alpha polymorphisms confer risk in EBV-infected patients.     

Human genetic variation and the risk of hepatocellular carcinoma development

Our understanding of the patho-physiology of hepatocellular carcinoma (HCC) is still much fragmented making difficult the improvement of the clinical outcome for the majority of HCC patients. Discovery of single nucleotide polymorphisms (SNPs) associated with individual susceptibility to HCC may enable the persons at risk to adapt their lifestyle and legitimate implementation by their doctors of surveillance programs facilitating early detection and subsequent management of the disease. To shed light on the influence of human genetic variation on HCC, we conducted a review of the meta-analyses of candidate SNPs and genome wide association studies (GWAS) performed for HCC by search of PubMed and Google Scholar databases. Genetic variations occurring in pathways historically considered as instrumental for liver tumorigenesis (TP53/MDM2, HLA, glutathione-S-transferases/cytochrome P540, TNFα/TGFβ, etc…) are discussed. An immense majority of the data has been produced in Eastern Asia (China, Japan, Korea). These meta-analyses indicate that the TP53, the MDM2 SNP309 G and the GSTT1 null genotype contribute to an increased risk of HCC both in Asians and Caucasians. Significant differences of odds ratios are, however, commonly observed between Eastern-Asians and other populations. Amazingly, GWAS studies performed so far exclusively with HCC patients from Eastern Asia produced drastically different outcomes pointing at unrelated biological pathways. The small magnitude of the risk associated with the genetic variants raises the question of their future utility as markers in clinical practice. An assessment of their impact on tumor progression (vascular invasion, metastases) remains, however, to be done and may prove to be more useful for clinicians. Finally, the evaluation of these variants is not available for various populations of the world and particularly for Subsaharan Africans who are especially affected by HCC.     

Association between interleukin-1β-511C/T polymorphism and reflux esophagitis in Japan

Background Interleukin-1β (IL-1β) gene polymorphisms are related to hypochlorhydria and increase the risk of gastric cancer in the presence of Helicobacter pylori infection. However, little information is available about the genetic risk factors of reflux esophagitis. In this study we investigated its association with the IL-1β polymorphisms. Methods We examined 48 patients with reflux esophagitis and 96 control subjects, 89 with gastric cancer. IL-1β-511C/T genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results The frequency of IL-1β-511T alleles was significantly higher in reflux esophagitis patients (57.3%) than in controls (41.1%) (P = 0.0215, χ² = 5.289). The frequency of IL-1β-511T/T genotypes was also significantly higher in reflux esophagitis patients (31.3%) than in controls (15.6%). The odds ratio and the 95% confidence interval were 4.000 and 1.393–11.486, respectively. The frequency of IL-1β-511T/T genotypes was significantly higher in reflux esophagitis patients (31.3%) than in gastric cancer patients (21.4%). The odds ratio and the 95% confidence interval were 2.961 and 1.054–8.316, respectively. Conclusions IL-1β-511T was associated with reflux esophagitis having hyperacidity. Differences of genetic background regarding gastric acid secretion may exist between Japanese and Caucasians.     

Genetic variants A1826H and D2937Y in GAG-β domain of versican influence susceptibility to intestinal-type gastric cancer

Purpose

Versican regulates adhesion, migration, proliferation, and survival of cells, and plays an important role in cancer development. A case–control association study was performed to test genetic association of versican polymorphisms with susceptibility to gastric cancer.

Methods

In this study, 1,101 unrelated Korean subjects including 612 gastric cancer patients and 489 healthy controls were genotyped for all 21 exonic polymorphisms in the versican gene (VCAN) encoding amino acid changes in versican. Cancer susceptibility associations with the polymorphisms were assessed using multivariate logistic regression analysis with adjustment for age and gender and with control for multiple testing.

Results

Two amino acid changes in GAG-β domain of versican encoded by two almost fully correlated (r ² = 0.97) nonsynonymous single-nucleotide polymorphisms in VCAN were associated with gastric cancer. The association was evident in intestinal-type but not in diffuse-type gastric cancer. The minor-allele homozygote of rs188703 (G > A, R1826H) or rs160277 (G > T, D2937Y) was significantly associated with a twofold decreased susceptibility to intestinal-type gastric cancer when compared with the other genotypes (adjusted odds ratio = 0.52 or 0.51, P = 0.0098 or 0.0087, respectively).

Conclusions

The intestinal-type gastric cancer susceptibility is associated with two amino acid changes of versican in the GAG-β domain, which is critical for enhancement of cell proliferation and activation of EGFR signal pathway by versican, and changes from the major to minor alleles may impair the function to decrease susceptibility to cancer.     

Genetics in rheumatoid arthritis beyond HLA genes: What meta-analyses have shown?

Objective

Rheumatoid arthritis (RA) is a complex disorder with many genetic and environmental factors to account for disease susceptibility. Individual genetic association studies usually suffer from small sample size leading to biased results of polymorphisms association with RA liability. Therefore, meta-analyses seem to resolve this limitation, up to a point, increasing the power of statistical analyses. In this review, we summarize the current knowledge of non-HLA genetic factors contributing to RA predisposition based on meta-analyses.

Methods

Using the key words: rheumatoid arthritis, meta-analysis, and polymorphism, we searched the PubMed database for the associated articles. Up to the middle of November 2012, seventy-nine articles fulfilled the criteria and highlighted the current findings on the genetic factors contributing to RA susceptibility.

Results

The association with RA was confirmed for 32 gene polymorphisms, being population specific in some cases. However, meta-analyses did not confirm an association in case of 16 gene variants, previously studied in individual studies for their association with RA.

Conclusions

The use of bioinformatics tools and functional studies of the summarized implicated genes in RA pathogenesis could shed light on the molecular pathways related to the disorder, helping to the development of new drug targets for a better treatment of RA.     

Interleukin 12B gene polymorphisms and susceptibility to rheumatoid arthritis: a data synthesis

The aim of this study was to investigate the association of two common interleukin 12B (IL-12B) polymorphisms (rs3212227 and rs6887695) with rheumatoid arthritis (RA) susceptibility through meta-analyses. A systematic literature search of PubMed, Web of Science, Cochrane Library, and Embase databases was conducted on articles published before 28 February 2016. Then odds ratio (OR) with 95 % confidence interval (CI) was used to quantify the strength of association for homozygote, heterozygote, dominant, and recessive genetic models. Nine articles with a total of 17 case–control studies (12 for IL-12B rs3212227 polymorphism and 5 for IL-12B rs6887695 polymorphism) met our inclusion criteria. The pooled results demonstrated that IL-12B rs3212227 (homozygote model: OR?=?0.96, 95 % CI?=?0.81–1.15; heterozygote model: OR?=?1.07, 95 % CI?=?0.93–1.23; dominant model: OR?=?1.05, 95 % CI?=?0.91–1.20; recessive model: OR?=?0.93, 95 % CI?=?0.79–1.10) and rs6887695 (homozygote model: OR?=?1.01, 95 % CI?=?0.84-1.21; heterozygote model: OR?=?1.14, 95 % CI?=?0.86–1.51; dominant model: OR?=?1.14, 95 % CI?=?0.87–1.48; recessive model: OR?=?1.01, 95 % CI?=?0.85–1.21) polymorphisms may not be associated with RA risk. Our meta-analyses demonstrated that IL-12B rs3212227 and rs6887695 polymorphisms do not confer susceptibility to RA.     

Relationship between IL-1β gene polymorphism and gastric mucosal IL-1β levels in patients with Helicobacter pylori infection

Background Interkeukin-1 (IL-1) gene cluster polymorphisms that are thought to enhance the production of IL-1β are associated with an increased risk of gastric cancer. To determine the role of host genetic factors in Helicobacter pylori infection, we examined the relationship between gastric mucosal IL-1β levels and IL-1B polymorphisms in patients with H. pylori infection.Methods Biopsy tissues obtained from 99 patients were homogenized and gastric mucosal IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA). Single-base polymorphisms at positions −511 and −31 in IL-1B were analyzed.Results The IL-1β level in the antrum was significantly higher in genotype IL-1B-511C/C than in H. pylori-negative patients (P < 0.05). The IL-1B polymorphism did not influence the degree of gastric neutrophil and mononuclear cell infiltration, or gastric atrophy. IL-1β levels in the corpus, but not those in the antrum, correlated to the severity of gastric atrophy.Conclusions These findings indicate that IL-1B polymorphisms enhance IL-1β production in the antrum; however, other factors might regulate the production of IL-1β in the corpus of the stomach, regardless of IL-1B polymorphisms, and high IL-1β production may be associated with the grade of gastric atrophy in the corpus mucosa in patients with H. pylori infection.     

Association of folate metabolism-related genetic polymorphisms with susceptibility to breast cancer: A protocol for a systematic review and meta-analysis

Background:Breast cancer has recently become one of the most common causes of cancer-related deaths, and several studies have suggested that genetic polymorphisms in the folate metabolism pathway may be associated with susceptibility to breast cancer, although their results have been inconsistent or inconclusive. Therefore, the aim of this meta-analysis was to obtain accurate, consistent conclusions regarding the potential associations of genetic polymorphisms in the folate metabolism pathway with the risk of breast cancer, based on case-controlled studies.Methods:From the beginning of database establishment through May 2021, we indexed and searched domestic and foreign databases, including the Chinese National Knowledge Infrastructure, Web of Science, VIP and BioMedical Database of China, PubMed, EMBASE, Wanfang database, and the Cochrane Library. To determine the effects of folate metabolism-related genetic polymorphisms on breast cancer risk, we used Stata version 16.0 to analyze all data and calculated variable odds ratios and 95% confidence intervals.Results:The findings of the current meta-analysis are going to be presented to peer-reviewed journals for publication when the analysis is completed.Conclusion:The meta-analysis will summarize the association of genetic polymorphisms in the folate metabolism pathway with breast cancer.Registration number:May 26, 2021.osf.io/25r48. (https://osf.io/25r48/).     

Role of environmental and genetic factor interaction in age-related disease development: the gastric cancer paradigm

The association of Helicobacter pylori (Hp) infection with gastric cancer is well known and might be considered a paradigmatic example of the role that interaction among environmental factors and individual background might play in inducing age-associated disease. To evaluate the role of interaction of Hp infection with genetic background, gastric cancer and chronic gastritis patients as well as random selected controls were typed for five inflammation-related polymorphisms of IL-1 and IL-10 cytokine genes. No association among IL-10 or IL-1 variants with an increased risk of gastric cancer was found, whereas an Hp-independent association of IL-1beta -511T positive genotypes to an increased risk of chronic gastritis was found (Hp-/511T+ OR 1.89, 95% CI: 1.01-3.54; Hp+/-511T+ OR 1.83, 95% CI: 1.05-3.19). Stratification of gastric cancer group according to Hp infection does not allow finding a statistically significant association of Hp+ to the higher histological grading (G3) of gastric cancer (OR 1.54, 95% CI: 0.46-5.11). Our findings seem to confirm that cytokine genetic variants might contribute to determining the background for inflammaging in which H. pylori infection might facilitate cancer development.     

CLPTM1L Genetic Polymorphisms and Interaction With Smoking and Alcohol Drinking in Lung Cancer Risk: A Case–Control Study in the Han Population From Northwest China

Genetic variants of cleft lip and palate trans-membrane 1-like (CLPTM1L) genes in the p15.33 region of chromosome 5 were previously identified to influence susceptibility to lung cancer. We examined the association of single nucleotide polymorphisms (SNPs) in CLPTM1L genes with lung cancer and explored their potential effects on the relationship between environmental risk factors (smoking, drinking) and lung cancer in a Chinese Han population.We genotyped 9 single nucleotide polymorphisms (SNPs) of CLPTM1L in a case–control study with 228 lung cancer cases and 301 controls from northwest China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression.We identified that the minor alleles of rs451360, rs402710, and rs31484 in CLPTM1L were associated with a 0.52-fold, 0.76-fold, and 0.70-fold decreased risk of lung cancer in allelic model analysis, respectively. In the genetic model analysis, we found rs402710 and rs401681 were associated with decreased lung cancer risk. Further stratification analysis showed that rs380286 displayed a significantly decreased lung cancer risk (OR = 0.65, P = 0.041) in the non-drinkers. In addition, Haplotype “GTTATCTGT” was found to be associated with decreased lung cancer risk (OR = 0.50, P = 0.033).Our results verified that genetic variants of CLPTM1L contribute to lung cancer susceptibility in the northwest Chinese Han population. Additionally, we found that consumption of alcohol may interact with CLPTM1L polymorphisms to contribute to overall lung cancer susceptibility.     

Causal role of Helicobacter pylori infection in gastric cancer

Gastric cancer is the second most frequent cancer in the world, accounting for a large proportion of all cancer cases in Asia, Latin America, and some countries in Europe. Helicobacter pylori(H pylori) is regarded as playing a specific role in the development of atrophic gastritis, which represents the most recognized pathway in multistep intestinal-type gastric carcinogenesis. Recent studies suggest that a combination of host genetic factors, bacterial virulence factors, and environmental and lifestyle factors determine the severity of gastric damage and the eventual clinical outcome of H pylori infection. The seminal discovery of H pylori as the leading cause of gastric cancer should lead to effective eradication strategies. Prevention of gastric cancer requires better screening strategies to identify candidates for eradication.     

CD24 genetic variants contribute to overall survival in patients with gastric cancer

AIM: To investigate the role of single nucleotide polymorphisms(SNPs) in CD24 gene in susceptibility and overall survival of gastric cancer(GC).METHODS: We genotyped 3 tagging SNPs of CD24-P-534 in the promoter region, P170 in the coding region of exon 2 and P1527 in the 3′ untranslated region- using polymerase chain reaction-restriction fragment length polymorphism in specimens from 679 histologically-confirmed GC cases, 111 gastric atrophy(GA) cases and 976 tumor-free controls. Serumimmunoglobulin G antibodies to Helicobacter pylori(H. pylori) of all subjects were detected by enzyme-linked immunosorbent assay. CD24 expression was evaluated by immunohistochemistry in 131 GC specimens. Correlations between SNPs and risk of GC or GA were shown by P values and odd ratios(ORs) with 95% confidence intervals(95%CI) compared with the most common genotype of each SNP using the unconditional logistic regression model after adjusting for age, sex and H. pylori infection. Survival within each SNP group was plotted by Kaplan-Meier method and compared by log-rank test(recessive model). Hazard ratios with 95%CIs were computed by Cox regression model after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy.RESULTS: All of the three loci were in Hardy-Weinberg equilibrium in the control group. Median followup time for the 600 GC patients included in the survival analysis was 36.2 mo(range, 2.1-66.7 mo; 95%CI: 34.3-36.5 mo). Patients with the P-534 A/A genotype had significantly shorter survival(HR = 1.38, 95%CI: 1.01-1.88, P = 0.042) than did the C/C or C/A genotype carriers after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. This trend was more evident in patients who lived longer than 2.5 years(HR = 7.55, 95%CI: 2.16-26.32, P = 0.001). The P170 T/T genotype was associated with a shorter lifespan than the non-T/T genotypes, but not significantly so. None of the three genetic variants was found to be associated with risk of GC(including tumor stage, grade and distant metastasis) or with risk of gastric atrophy. Furthermore, no difference of CD24 expression was found among the genotypes.CONCLUSION: The P-534 site in CD24 gene affects the overall survival of gastric cancer and may serve as a prognostic marker for gastric cancer.     

Circulating IL-1β levels, polymorphisms of IL-1B, and risk of cervical cancer in Chinese women

Purpose

Long-term human papillomavirus (HPV) infection is a prerequisite for cervical cancer. IL-1β and IL-1Ra expression levels play an important role in cervical carcinogenesis. Several functional genetic variants in IL1B and IL-RN have been reported to be associated with IL-1β expression and cancer susceptibility. In the current study, we hypothesized that plasma IL-1β levels, IL-1B and IL-RN polymorphisms were candidate biomarkers for cervical cancer.

Methods

We measured plasma IL-1β levels and genotyped IL-1B and IL-RN polymorphisms in a case–control study of 404 cervical cancer cases and 404 controls in Chinese women.

Results

The mean plasma IL-1β levels in cervical cancer cases (42.19 ± 31.55 pg/ml) was significantly higher than those in controls (34.86 ± 22.68 pg/ml, P = 0.0002), and plasma IL-1β levels above the 75% quartiles in controls (IL-1β ≥ 46.94 pg/ml) were associated with a 1.74-fold significantly increased risk of cervical cancer [95% confidence interval (CI), 1.28–2.36], compared with those of lowest quartile. Multivariate logistic regression analyses revealed that the variant genotypes, IL-1B T-31C TC/CC and C-511T CT/TT, were associated with a significantly increased risk of cervical cancer [adjusted odds ratio (OR), 1.60; 95% CI, 1.16–2.21 for ?31TC/CC, and adjusted OR, 1.52; 95% CI, 1.10–2.09 for ?511CT/TT, respectively), especially among subjects having higher levels of IL-1β. However, IL-RN VNTR polymorphism was not associated with cervical cancer risk in the current study. Furthermore, the significant differences of IL-1β concentration between cervical cancer cases and controls were observed only among subjects carrying T-31C or C-511T variant genotypes.

Conclusion

Functional IL-1B genotypes may modify plasma IL-1β concentrations to contribute to the etiology of cervical cancer in Chinese women; however, further perspective studies are warranted to test the causal effects of IL-1β concentration in cervical carcinogenesis.     

Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population

AIM: To investigate the association between the tag single nucleotide polymorphisms (TagSNPs) of NOD1 and NOD2 and the risk of developing gastric cancer.METHODS: We conducted a hospital-based case-control study including 296 incident gastric cancer patients and 160 gastritis controls. Eight TagSNPs in the NOD1 and NOD2 genes were selected from the Hapmap database using the haploview software and genotyped by the Sequenom MassArray system. The serum levels of anti-Helicobacter pylori (H. pylori) IgG were measured by enzyme-linked immunosorbent assay to indicate H. pylori infection. The odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression, including sex and age as confounding factors.RESULTS: The NOD1 rs2907749 GG genotype showed a decreased risk for gastric cancer (OR 0.50, 95% CI: 0.26-0.95, P = 0.04) while the rs7789045 TT genotype showed an increased risk (OR 2.14, 95% CI: 1.20-3.82, P = 0.01). An elevated susceptibility to gastric cancer was observed in the subjects with H. pylori infection and the NaOD1 rs7789045 TT genotype (OR 2.05, 95% CI: 1.07-3.94, P = 0.03) or the NOD2 rs7205423 GC genotype (OR 2.52, 95% CI: 1.05-6.04, P = 0.04). Haplotype analysis suggested that the distribution of AGT (rs2907749, rs2075820 and rs7789045) in NOD1 between the cases and control groups was significantly different (P corrected: 0.04), and the diplotype AGT/AGT was associated with an elevated gastric cancer risk (OR 1.98, 95% CI: 1.04-3.79, P = 0.04). The association of the NOD1 rs7789045 TT genotype and the diplotype AGT/AGT was significant with H. pylori-related diffuse-type gastric cancer (OR 3.00, 95% CI: 1.38-6.53, P = 0.01; OR 4.02, 95% CI: 1.61-10.05, P < 0.01, respectively).CONCLUSION: Genetic polymorphisms in NOD1 and NOD2 may interact with H. pylori infection and may play important roles in promoting the development of gastric cancer in the Chinese population.     

IRGM gene polymorphisms and risk of gastric cancer

OBJECTIVE: The study aimed to assess the possible association of polymorphisms in the autophagy gene IRGM (rs13361189 and rs4958847) with the risk of gastric cancer. METHODS: A total of 102 patients with gastric adenocarcinoma, 52 with chronic gastritis and 351 healthy controls were included in this study. IRGM allelic variants were genotyped by quantitative real‐time polymerase chain reaction. The association between polymorphisms and gastric cancer risk was estimated by odds ratios (OR) and 95% confidence interval (CI). RESULTS: A significant difference was found for rs4958847 A allele. Carriers of the A allele were protected against gastric cancer (OR = 0.58, 95% CI 0.35–0.97, P = 0.038). Moreover, the presence of this allele seems to play an important role in decreasing the risk for the intestinal type of gastric cancer (OR = 0.47, 95% CI 0.23–0.94, P = 0.03). In contrast, the rs13361189 IRGM polymorphism was not associated with susceptibility to gastric cancer. None of the targeted polymorphisms were associated with chronic gastritis. CONCLUSION: IRGM rs4958847 polymorphism influences susceptibility to gastric cancer, mainly for the intestinal type.