Population-based Subgroup Research Articles

Vitamin D Deficiency Prevalence in Pakistan: Common, Important, and Neglected: A Comprehensive Meta-Analysis

Abstract Vitamin D is crucial for normal body metabolism. Two important vitamin D sources are synthesis in the lower layers of the skin (90%) and diet (10%). This systematic review and meta-analysis attempted to determine the incidence of vitamin D deficiency in Pakistan by using the findings of numerous cross-sectional studies. For subgroup analysis, a population-based subgroup analysis and a geographical location-based subgroup analysis were done. Different search techniques were utilized on various databases using the terms “vitamin D deficiency,” “Pakistan,” and “prevalence.” The article names and abstracts were scrutinized, and associated complete texts were evaluated. The articles that satisfied the inclusion requirements were chosen for the meta-analysis. The I 2 test was used to determine heterogeneity. They were combined with the random-effect method. Out of 429 articles, 37 studies, with a total sample size of 19,338, were selected for the final analysis. The highest and lowest reported percentages observed were 100% and 15%, respectively. The overall pooled prevalence reported was 78% (95% CI = 74.2–82%). In subgroup analysis, children/adolescents showed a higher pooled prevalence of 84% (95% CI = 76.1–93.6%), and among province-wise subgroup analysis, Punjab province has shown a higher pooled prevalence of 84% (95% CI: 74–94%). Meta-analysis of the data showed a higher proportion of the population with deficient states. Interventions in public health are essential to address the high incidence of vitamin D insufficiency. Vitamin D levels can be increased, and related health concerns can be minimized through dietary supplementation, recommended sun exposure, and awareness initiatives.

Meta-Analysis of Vitamin D Receptor Gene Polymorphisms in Childhood Asthma.

We conducted the systematic review to investigate the potential relationship between the vitamin polymorphisms of D receptor (VDR) gene and childhood asthma. Relevant studies researching on VDR polymorphisms and asthma susceptibility were searched throughout Embase, PubMed, China Science and technology journal database (CQVIP), etc. till 12 April, 2021. We calculated the pooled odds ratios (OR) and its 95% confidence interval (CI) using RevMan 5.3 software and Stata 11.0. FokI (rs2228570) could significantly affect childhood asthma risk across co dominant model (Ff vs. FF: OR (95%CI) = 0.82 (0.65, 1.02), P = 0.071) and dominant model (ff+Ff vs. FF: OR (95%CI) = 0.77 (0.63, 0.95), P = 0.016), especially among Caucasians in additive model (f vs. F: OR (95%CI) = 0.63 (0.43, 0.92), P = 0.015) and dominant model (ff+Ff vs. FF: OR (95%CI) = 0.67 (0.51, 0.88), P = 0.004). TaqI (rs731236) was significantly related with childhood asthma in additive model (t vs. T: OR (95%CI) = 0.45 (0.23, 0.89), P = 0.022), co dominant model (Tt vs. TT: OR (95%CI) = 0.36 (0.17, 0.77), P = 0.009), and dominant model (tt+Tt vs. TT: OR (95%CI) = 0.36 (0.15, 0.87), P = 0.024) among Asian, as well as population-based subgroup in co dominant model (Tt vs. TT: OR (95%CI) = 0.53 (0.31, 0.94), P = 0.029). However, no evidence supported the role of ApaI (rs7975232) and BsmI (rs1544410) polymorphisms in childhood asthma. FokI and TaqI polymorphisms were found to be related with the susceptibility of childhood asthma. However, it seems that ApaI and BsmI polymorphisms are not related with childhood asthma susceptibility.

Effect of miR-196a2 rs11614913 Polymorphism on Cancer Susceptibility: Evidence From an Updated Meta-Analysis.

Background: MiR-196a2 rs11614913 polymorphism has been studied in a wide range of cancers throughout the years. Despite a large number of epidemiological studies performed in almost all ethnic populations, the contribution of this polymorphism to cancer risk is still inconclusive. Therefore, this updated meta-analysis was performed to estimate a meticulous correlation between miR-196a2 rs11614913 variant and cancer susceptibility. Methods: A systematic study search was carried out using PubMed, ScienceDirect, CNKI, EMBASE, Scopus, and Google Scholar databases following PRISMA guidelines to find necessary literature up to December 15, 2021. Pooled odds ratios with corresponding 95% confidence intervals were estimated using RevMan 5.4 based on ethnicities, cancer types, control sources, and genotyping methods. Results: A total of 152 studies, including 120 135 subjects (53 818 patients and 66 317 controls; 140 studies, after removing studies that deviated from HWE: 51 459 cases and 62 588 controls), were included in this meta-analysis. Quantitative synthesis suggests that the miR-196a2 rs11614913 genetic variant is significantly correlated with the reduced risk of overall cancer in CDM2, CDM3, RM, and AM (odds ratio < 1 and P < .05). It is also observed from ethnicity-based subgroup analysis that rs11614913 polymorphism is significantly (P < .05) linked with cancer in the Asian (in CDM2, CDM3, RM, AM) and the African population (in CDM1, CDM3, ODM). Stratified analysis based on the cancer types demonstrated a significantly decreased correlation for breast, hepatocellular, lung, and gynecological cancer and an increased association for oral and renal cell cancer. Again, the control population-based subgroup analysis reported a strongly reduced correlation for HB population in CDM2, RM, and AM. A substantially decreased risk was also observed for other genotyping methods in multiple genetic models. Conclusions: MiR-196a2 rs11614913 variant is significantly correlated with overall cancer susceptibility. Besides, rs11614913 is correlated with cancer in Asians and Africans. It is also correlated with breast, gynecological, hepatocellular, lung, oral, and renal cell cancer.

A Systematic Review and Meta-Analysis for the Association of Gene Polymorphisms in RAN with Cancer Risk.

As an important component of miRNA processing genes, RAN gene encodes the ras-related nuclear protein, which is a unique member of the Ras superfamily of GTPases. The mutations in RAN gene are very likely to play a critical role in pathology-related changes to miRNA transport and expression and thus participate in tumor genesis and development. Currently, accumulating studies have explored the association between RAN SNPs and cancer risk. However, the results are conflicting. In the present study, we performed a systematic review for the association of RAN SNPs with overall cancer risk. Meanwhile, a meta-analysis was conducted based on available data, aiming at clarifying the association between RAN SNPs and cancer susceptibility. After literature search and data extraction, 17 studies containing four RAN SNPs were involved in the systematic review. And 12 studies with two highly studied SNPs (RAN rs14035 C>T and rs3803012 A>G) were included in the final meta-analysis, consisting of 7662 cases and 9807 controls. The results showed that the rs14035 polymorphism was linked to a decreased cancer risk in overall subjects and hospital-based (HB) subgroup, while the rs3803012 polymorphism conferred to an increased cancer risk in overall subjects and population-based (PB) subgroup. Our findings suggested that the two SNPs had the potential to be predictive biomarkers for cancer risk. The study would provide novel clues for the identification of miRNA-related genetic biomarkers applied to predicting cancer susceptibility.

Flunarizine Induced Parkinsonism in Migraine Group: A Nationwide Population-Based Study.

Background: Flunarizine (Fz) is a first-line prophylactic medication that is widely used in migraine. However, Fz has been recognized as a potential cause of drug-induced parkinsonism for a long time. However, to our knowledge, there has been no population-based subgroup analyses for Fz-induced parkinsonism (FIP) in migraine patients. Methods: Data were obtained from the Taiwan’s National Health Insurance Research Database. The study comprised 6,470 migraine patients who were divided into two groups, based on their exposure or non-exposure to Fz. Results: During the study period (2000–2012), the incidence rate of parkinsonism was 1.92 and 8.72 per 1,000 person-years in the control and Fz -treated groups, respectively. In the study population, the adjusted hazard ratio was 4.07 (95% confidence interval CI: 2.84–5.85). In 45–64-year old subjects and ≥ 65-year old subjects, the risk of FIP was 3.18 times (95% CI = 1.63–6.20) and 4.89 times (95% CI = 3.09–7.72) more than that in the controls. The Fz-treated subjects with comorbidities also had a higher risk (4.54, 95% CI: 3.14-6.57). An average annual cumulative Fz dose > 445 mg was accompanied by the greatest risk of FIP; Fz use for >60 days is a cut-off point for predicting future FIP. Conclusion: At the population level, this study showed a complete picture of FIP in migraine patients. FIP is associated with older age, history of comorbidities, exposure to high-dose of Fz, and longer duration of exposure to Fz.

Subgroups of IBS patients are characterized by specific, reproducible profiles of GI and non-GI symptoms and report differences in healthcare utilization: A population-based study.

In a previous clinical sample of IBS patients, subgroups characterized by profiles of GI and non-GI symptoms were identified. We aimed to replicate these subgroups and symptom associations in participants fulfilling IBS diagnostic criteria from a population-based study and relate them to healthcare utilization. An Internet-based health survey was completed by general population adults from United States, Canada, and UK. Respondents fulfilling IBS diagnosis (Rome III and IV) were analyzed for latent subgroups using Gaussian mixture model analysis. Symptom measures were derived from validated questionnaires: IBS-related GI symptoms (Rome IV), extraintestinal somatic symptoms (PHQ-12), and psychological symptoms (SF-8). A total of 637 respondents fulfilled Rome III criteria (average age 46years, range 18-87, 66% females) and 341 Rome IV criteria (average age 44, range 18-77, 64% female) for IBS. Seven subgroups were identified in the Rome III cohort, characterized by profiles of GI symptoms (constipation-related, diarrhea-related, and mixed, respectively), and further distinguished by the presence or absence of non-GI comorbidities. The Rome IV cohort showed five similar but less distinct subgroups with a preponderance of mixed symptom profiles. Higher severity of non-GI comorbidities was associated with more frequent healthcare visits and medication usage. In line with previous findings in a clinical IBS cohort, we were able to identify population-based subgroups characterized by a combination of GI symptoms with the additional distinction made by varying severity of non-GI symptoms and with differences in healthcare utilization.

Predictive value of excision repair cross-complementing group 2 gene Lys751Gln and Asp312Asn polymorphisms in melanoma risk.

Epidemiological studies have assessed the association between excision repair cross-complementing group 2 (ERCC2) Lys751Gln and Asp312Asn polymorphisms and melanoma risk with conflicting results. Relevant articles were searched from PubMed, Embase, and Web of Science with a time limit of 3 September 2016. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. We performed this meta-analysis with 12 studies including 6157 cases and 8873 controls for Lys751Gln and nine studies including 5037 cases and 7542 controls for Asp312Asn polymorphism. Overall, no significant associations were found under all the models for Lys751Gln polymorphism, and significant associations were found for Asp312Asn polymorphism for AA versus GG (OR=1.12, 95% CI=1.00-1.26) and for the recessive model (OR=1.11, 95% CI=1.00-1.24). In the stratification analyses by source of control: for Lys751Gln polymorphism, significant associations were found for CC versus AA (OR=1.19, 95% CI=1.04-1.36) and the recessive model (OR=1.15, 95% CI=1.02-1.30); for Asp312Asn polymorphism, significant associations were found for AA versus GG (OR=1.31, 95% CI=1.11-1.53) and the recessive model (OR=1.29, 95% CI=1.11-1.50). This meta-analysis suggested that both the Lys751Gln and Asp312Asn polymorphisms were risk factors for melanoma risk in population-based subgroup.

Association between Krüppel like factor 6 intervening sequence 1-27 G > A and cancer susceptibility: A meta-analysis.

It has been reported that Krüppel like factor 6 intervening sequence (KLF6 IVS) 1-27 G > A might be associated with cancer susceptibility. Here, we conducted a meta-analysis to summarize and clarify this association. A systematic search of studies on the association between KLF6 IVS 1-27 G > A, and cancer susceptibility was conducted in databases. Odds ratios and 95% confidence intervals were used to pool the effect size. Seven articles were included in our meta-analysis. Overall and in prostate cancer, population-based subgroup overall and Caucasian subgroup overall, no evidence was found for the association between KLF6 IVS 1-27 G > A polymorphism and cancer susceptibility in any genetic model and the results showed stability in sensitivity analyses. KLF6 IVS 1-27 G > A may not be associated with cancer susceptibility, especially the susceptibility of unselected prostate cancer. However, there was insufficient data to fully confirm the association between KLF6 IVS 1-27 G > A and familial prostate cancer, sporadic prostate cancer, gastric cancer, and cancers from different ethnicity, and the results should be interpreted with caution.

Association between ERα gene Pvu II polymorphism and breast cancer susceptibility: A meta-analysis.

Background:Estrogen has played an important role in the development of breast cancer. ER-α PvuII gene polymorphism is in close association with the occurrence risk of breast cancer, but no consensus has been achieved currently.Methods:PubMed, Embase, China National Knowledge Infrastructure (CNKI) database, Wanfang database, and VIP database were retrieved to collect the case–control studies on association between ERα gene Pvu II polymorphism and breast cancer risk published before September 1, 2017. Newcastle–Ottawa Scale (NOS) was used to assess the quality of the literatures, Stata 14.0 software was applied for meta-analysis, and the pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated. The subgroup analysis was performed to assess the confounding factors, followed by assessment of publication bias and sensitivity analysis.Results:A total of 26 studies were enrolled in the analysis based on inclusion criteria, which included 15,360 patients and 26,423 controls. The results demonstrated that ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in 3 genetic models (C vs T, OR = 0.962, 95% CI = 0.933–0.992, P = .012; CC vs TT, OR = 0.911, 95% CI = 0.856–0.969, P = .003; CC vs TT/CT, OR = 0.923, 95% CI = 0.874–0.975, P = .004). Subgroup analysis was conducted on the basis of ethnicity and source of controls, whose results illustrated that ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in Asians rather than in Caucasians (CC vs TT, OR = 0.862, 95% CI = 0.750–0.922, P = .038; CC vs TT/CT, OR = 0.851, 95% CI = 0.755–0.959, P = .008). In population-based subgroup rather than in hospital-based subgroup, ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in the allele model, homozygous model, dominant model, and recessive model (C vs T, OR = 0.943, 95% CI = 0.911–0.977, P = .001; CC vs TT, OR = 0.878, 95% CI = 0.817–0.944, P = .000; CC/CT vs TT, OR = 0.936, 95% CI = 0.881–0.994, P = .031; CC vs TT/CT, OR = 0.902, 95% CI = 0.847–0.960, P = .001).Conclusion:ERα gene Pvu II polymorphism exerts an important function in the progression of breast cancer.

OncomiR-27a rs895819 variant and breast cancer risk: An updated meta-analysis

Recently the functional variant of precursor form of microRNA-27a (miR-27a: rs895819; n.40A>G) has been related to several cancers including breast cancer (BC), albeit with conflicting evidence. The current updated meta-analysis aimed to explore the possible association between this variant and BC risk based on more stratification analysis, correlation with the clinico-pathological and prognostic parameters and including more recent publications. Searches were carried out in PubMed and other databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate BC risk. In silico analysis of the structural and functional impact of the studied variant was also executed.A total of 12 eligible studies with 5441 BC patients and 6250 controls were enrolled. Overall analysis revealed no association between the rs895819 polymorphism and BC risk. However, on stratified analysis by ethnicity, a decreased risk was observed in the Caucasian population [OR (95% CI); G vs. A: 0.894 (0.823–0.970), AG vs. AA: 0.843 (0.753–0.943), and AG/GG vs. AA: 0.850 (0.763–0.947)]. Subgroup analysis revealed a protective effect of G variant in patients with familial BC [G vs. A: 0.89 (0.83–0.97)], among population-based subgroup [G vs. A: 0.92 (0.86, 0.98)], patients´ young age [G vs. A: 0.85 (0.78, 0.94)] and BRCA1/2 negative mutations [G vs. A: 0.89 (0.82, 0.96)]. No association with patients' age, pathological cancer type, or HER2 hormonal receptors was detected. However, patients with AG/GG genotypes were shown to be more likely to have tumor tissue with positive estrogen receptors under a dominant model (AG/GG vs. AA: OR = 1.59, 95% CI = 1.09–2.33). In conclusion overall miR-27a (rs895819) polymorphism was not associated with BC risk. However, the rs895819*G variant may confer protection against cancer in Caucasian and familial BC. Well-designed studies with larger cohorts in diverse ethnic populations are warranted.

Milk/dairy products consumption and gastric cancer: an update meta-analysis of epidemiological studies.

The relationship between dairy consumption and gastric cancer risk has not been well studied. We therefore performed a update meta-analysis to evaluate the relationship. Published cohort and case-control studies were identified via computer searches and reviewing the reference lists of the key articles. Random effects meta-analysis was used to pool effects from 5 cohort and 29 case-control studies. The odds ratio for the overall association between dairy consumption and gastric cancer was 1.20 (95%confidence interval: 1.04–1.39). The combined risk estimate was similar for population-based case-control studies (odds ratio = 1.27, 95%confidence interval: 1.00–1.61), but was reduced for hospital-based studies (odds ratio = 1.22; 95%confidence interval: 0.95–1.57) and cohort studies (odds ratio = 0.99; 95%confidence interval: 0.77–1.28). There was high heterogeneity in overall analyses. In the population-based subgroup analyses, the odds ratio was 0.96 (95%confidence interval: 0.69–1.34) when considering five studies assessing exposure two or more years before interview, and the association strengthened (odds ratio = 1.91, 95%confidence interval: 1.60–2.28) when dairy consumption was evaluated one year or less prior to interview. In conclusion, we found adverse effect of dairy consumption associated with gastric cancer.

Association between miR-146a single nucleotide polymorphism and genetic susceptibility to hepatocellular carcinoma: a meta-analysis

Objective: To investigate the association between miR-146a single nucleotide polymorphism and genetic susceptibility to hepatocellular carcinoma (HCC). Methods: PubMed, Web of Science, Cochrane Library, Wanfang Data, and Google Scholar were searched for case-control studies on the association between miR-146a single nucleotide polymorphism and genetic susceptibility to HCC published up to October, 2016 in Chinese or English. The Q-statistics test was used to evaluate the heterogeneity of these articles. Results: A total of 18 articles with 5 610 cases and 7 531 controls were included for the meta-analysis. There was no significant association between miR-146a single nucleotide polymorphism and genetic susceptibility to HCC. The odds ratio (OR), 95% confidence interval (95% CI), and P values for the five genetic models were as follows: the allele model C/G (OR = 0.99, 95% CI 0.88-1.06, P = 0.440); the heterozygous model CG/GG (OR = 0.99, 95% CI 0.90-1.10, P = 0.898); the homozygous model CC/GG (OR = 0.91, 95% CI 0.75-1.10, P = 0.314); the dominant model CC+CG/GG (OR = 0.97, 95% CI 0.79-1.19, P = 0.759); the recessive model CG+GG/CC (OR = 1.05, 95% CI 0.94-1.18, P = 0.405). A subgroup analysis of race, source of control population, and Hardy-Weinberg equilibrium were performed in these five genetic models, and miR-146a single nucleotide polymorphism increased the susceptibility to HCC only in the control population-based subgroups of the recessive model CG+GG/CC (OR = 1.20, 95% CI 1.02-1.40, P = 0.024). There was no association between miR-146a rs2910164 polymorphism and susceptibility to HCC in all the other subgroups. A stratified analysis of HBV infection revealed that miR-146a rs2910164 polymorphism increased the risk of HBV-positive HCC (OR = 1.26, 95% CI 1.10-1.49, P = 0.001). Conclusion: There is no significant association between miR-146a rs2910164 polymorphism and the risk of HCC, but miR-146a rs2910164 polymorphism may increase the risk of HBV-positive HCC.

Quantitative assessment of the association between XRCC1 Arg399Gln and Arg194Trp polymorphisms and risk of cutaneous melanoma.

Accumulating evidence has suggested that the XRCC1 Arg399Gln and Arg194Trp polymorphisms might be related to cutaneous melanoma susceptibility. However, epidemiologic findings have been inconsistent. We have assessed reported studies by meta-analysis to perform a more precise estimation of the association between the XRCC1 two polymorphisms (Arg399Gln, Arg194Trp) and risk of cutaneous melanoma. A total of seven eligible articles were selected for this meta-analysis, including 3454 cases and 3811 controls for the XRCC1 Arg399Gln polymorphism and 1256 cases and 1575 controls for the XRCC1 Arg194Trp polymorphism. Overall, no significant associations were found in all genetic models when the studies were pooled into the meta-analysis for the Arg399Gln and Arg194Trp polymorphisms. When stratified by source of control, significant associations were found for the Arg399Gln polymorphism in the population-based subgroup under AA versus GG [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.08-1.88]; the dominant model AA/GA versus GG (OR=1.25, 95% CI=1.04-1.51); and the recessive model AA versus GA/GG (OR=1.31, 95% CI=1.01-1.68). No significant associations were found for the Arg194Trp polymorphism in the subgroup analysis. This meta-analysis suggested that the XRCC1 Arg399Gln polymorphism was a risk factor for cutaneous melanoma in population-based subgroup.

Programmed Cell Death-1 Polymorphisms Decrease the Cancer Risk: A Meta-Analysis Involving Twelve Case-Control Studies.

Programmed cell death-1 (PD-1) plays an important inhibitory role in anti-tumor responses, so it is considered as a powerful candidate gene for individual’s genetic susceptibility to cancer. Recently, some epidemiological studies have evaluated the association between PD-1 polymorphisms and cancer risk. However, the results of the studies are conflicting. Therefore, a meta-analysis was performed. We identified all studies reporting the relationship between PD-1 polymorphisms and cancers by electronically searches. According to the inclusion criteria and the quality assessment of Newcastle-Ottawa Scale (NOS), only high quality studies were included. A total of twelve relevant studies involving 5,206 cases and 5,174 controls were recruited. For PD-1.5 (rs2227981) polymorphism, significantly decreased cancer risks were obtained among overall population, Asians subgroup and population-based subgroup both in TT vs. CC and TT vs. CT+CC genetic models. In addition, a similar result was also found in T vs. C allele for overall population. However, there were no significant associations between either PD-1.9 (rs2227982) or PD-1 rs7421861 polymorphisms and cancer risks in all genetic models and alleles. For PD-1.3 (rs11568821) polymorphism, we found different cancer susceptibilities between GA vs. GG and AA vs. AG+GG genetic models, and no associations between AA vs. GG, AA+AG vs. GG genetic models or A vs. G allele and cancer risks. In general, our results firstly indicated that PD-1.5 (rs2227981) polymorphism is associated a strongly decreased risk of cancers. Additional epidemiological studies are needed to confirm our findings.

Quantitative assessment of the influence of X-ray repair cross-complementing group 3 rs861539 polymorphism and cutaneous melanoma susceptibility.

Previous studies evaluating the association between X-ray repair cross-complementing group 3 (XRCC3) rs861539 polymorphism and cutaneous melanoma susceptibility reported conflicting findings. To draw a more precise association between XRCC3 rs861539 polymorphism and cutaneous melanoma susceptibility, we searched PubMed, EMBASE and Web of Science for case-control studies. A total of eight case-control studies including 3463 cases of melanoma and 4216 controls were included in the meta-analysis. Overall, no significant associations were found between XRCC3 rs861539 polymorphism and cutaneous melanoma susceptibility under all four genetic models (TT vs CC: OR 0.99, 95% CI 0.86-1.14; TC vs CC: OR 0.92, 95% CI 0.83-1.01; dominant model: OR 0.94, 95% CI 0.85-1.03; recessive model: OR 1.05, 95% CI 0.92-1.19). In the subgroup by source of control, no significant associations were found in hospital-based and population-based subgroup. This meta-analysis suggested that the XRCC3 rs861539 polymorphism was not a risk factor for cutaneous melanoma susceptibility.

Interleukin-1B 31 C>T polymorphism combined with Helicobacter pylori-modified gastric cancer susceptibility: evidence from 37 studies.

Gastric cancer is one of the most common malignancies worldwide. Interleukin-1-beta (IL-1β) is a pro-inflammatory cytokine and potent inhibitor of gastric acid secretion. Some studies provided evidence of the association between IL-1B 31 polymorphism and gastric cancer risk while other studies did not. Therefore, we conducted a comprehensive meta-analysis to reassess the association. A systematic literature search of the PubMed and EMBASE databases identified 37 studies with 6108 cases and 8980 controls for this meta-analysis. The crude odd ratios (ORs) and the 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Meta-regression was used to determine the major source of heterogeneity across the studies. The pooled analysis did not suggest the significant association of IL-1B 31 C>T polymorphism with gastric cancer risk. Stratified analysis was performed by ethnicity, source of control, genotype method, and indicated a significantly increased gastric cancer risk associated with IL-1B 31T variant in the population-based subgroup (heterozygous model: OR = 1.22, 95% CI = 1.03-1.45). Moreover, stratified analysis by Helicobacter pylori infection status indicated that IL-1B 31 polymorphism increased gastric cancer risk in infection-positive subgroup (homozygous model: OR = 1.35, 95% CI = 1.02-1.78; heterozygous model: OR = 1.31, 95% CI = 1.04-1.66; recessive model: OR = 1.29, 95% CI = 1.04-1.61). The study suggested that IL-1B 31 polymorphism might confer susceptibility to gastric cancer in the presence of H. pylori infection, indicating a gene-environment interaction in gastric carcinogenesis.

GSTT1 Null Genotype Significantly Increases the Susceptibility to Urinary System Cancer: Evidences from 63,876 Subjects

GSTT1 gene plays an important role in detoxification and clearance of reactive oxygen species(ROS). A null variant in this gene has been demonstrated to confer cancer susceptibility. Although many studies have demonstrated the association between GSTT1 null polymorphism and urinary system cancer susceptibility, several publications reported opposite conclusions. For better understanding the effects of this polymorphism on the risk of urinary system cancer, a updated meta-analysis was performed with a total of 26,666 cases and 37,210 controls extracted from 117 studies, by following the latest meta-analysis guidelines (PRISMA). The results suggested that the GSTT1 null genotype was significantly associated with an increased risk of urinary system cancer (OR=1.13, 95%CI=1.05-1.22). Furthermore, stratified analyses by the type of cancer, ethnicity, source of control and quality score presented a significantly increased risk associated with GSTT1 null genotype in bladder and prostate cancer subgroup, Caucasians and Indians subgroup, population-based(PB) subgroup, medium quality and low quality subgroup. Overall, our meta-analysis suggested that GSTT1 null genotype is a potential cancer susceptibility variant. Well-designed and large-cohort studies are needed to confirm the association between GSTT1 null genotype and urinary system cancer risk.

Association Between COX-2 Polymorphisms and Lung Cancer Risk.

BackgroundMultiple relevant risk factors for lung cancer have been reported in different populations, but results of previous studies were not consistent. Therefore, a meta-analysis is necessary to summarize these outcomes and reach a relatively comprehensive conclusion.Material/MethodsSTATA 12.0 software was used for all statistical of the relationship between COX-2 polymorphisms and lung cancer risk. Inter-study heterogeneity was examined with the Q statistic (significance level at P<0.1). The publication bias among studies in the meta-analysis was analyzed with Begg’s funnel plot and Egger’s test. Hardy-Weinberg equilibrium was tested in all controls of the studies.ResultsCOX-2 rs20417 polymorphism had a significant association with reduced risk of lung cancer under homozygous and recessive models, and similar results were observed in white and population-based subgroups under 2 and 3 contrasts, respectively. Additionally, rs2066826 polymorphism manifested a strong correlation with increased risk of lung cancer under 5 genetic models.ConclusionsIn COX-2 gene, rs20417 may have a certain relationship with reduced risk of lung cancer, while rs2066826 may increase the risk of lung cancer.

Quantitative assessment of the association between DNMT3B-579G>T polymorphism and cancer risk.

DNA methyltransferase 3B (DNMT3B) has been discovered to play an important role in tumorigenesis. However, the association between DNMT3B-579G>T and the cancer risk has not been demonstrated. The aim of this study is to provide a precise quantification for the association between DNMT3B-579G>T and the cancer susceptibility. We performed a systematic literature review and assessed the methodological quality of included case-control designed studies based on Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated to assess the strengths of the association. We identified 18 studies for pooled analyses. Overall, the results demonstrated that the DNMT3B-579G>T polymorphism was significantly associated with a subtly decreased cancer risk (GT vs TT: OR = 0.78, 95%CI: 0.70-0.87, P< 0.01; GT + GG vs TT: OR = 0.81, 95%CI: 0.68-0.97, P= 0.02), especially in the Asian population and in colorectal cancer subgroup. In addition, when stratified for source of controls, the results of population-based subgroup showed the GT genotype might have a significantly decreased cancer risk, but not hospital-based subgroups. DNMT3B-579G>T polymorphism might contribute to the susceptibility of cancers especially in the Asian population and for colorectal cancer.

Meta-analyses of gene methylation and smoking behavior in non-small cell lung cancer patients.

Aberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCLC). However, inconsistent findings existed among the recent association studies between cigarette smoking and gene methylation in lung cancer. The purpose of our meta-analysis was to evaluate the role of gene methylation in the smoking behavior of NSCLC patients. A total of 116 genes were obtained from 97 eligible publications in the current meta-analyses. Our results showed that 7 hypermethylated genes (including CDKN2A, RASSF1, MGMT, RARB, DAPK, WIF1 and FHIT) were significantly associated with the smoking behavior in NSCLC patients. The further population-based subgroup meta-analyses showed that the CDKN2A hypermethylation was significantly associated with cigarette smoking in Japanese, Chinese and Americans. In contrast, a significant association of RARB hypermethylation and smoking behavior was only detected in Chinese but not in Japanese. The genes with altered DNA methylation were likely to be potentially useful biomarkers in the early diagnosis of NSCLC.