A number of researchers have reported that vasectomy is a risk factor for testicular cancer. However, this conclusion is inconsistent with a number of other published articles. Hence, we conducted this meta-analysis to assess whether vasectomy increases the risk of testicular cancer.We identified all related studies by searching the PubMed, Embase, and Cochrane Library database from January 01, 1980 to June 01, 2017. The Newcastle-Ottawa Scale (NOS) checklist was used to assess all included non-randomized studies. Summarized odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the difference in outcomes between case and control groups. Subgroup analyses were performed according to the study design and country.p values > 0.05, respectively.A total of eight studies (2176 testicular cancer patients) were included in this systematic review and meta-analysis. Six articles were case-control studies, and two were cohort studies. The pooled estimate of the OR was 1.10 (95% CI: 0.93–1.30) based on the eight studies in a fixed effects model. Two subgroup analyses were performed according to the study design and country. The results were consistent with the overall findings. Publication bias was detected by Begg’s test and Egger’s test and Our meta-analysis suggested that there was no association between vasectomy and the development of testicular cancer. More high-quality studies are warranted to further explore the association between vasectomy and risk of testicular cancer. Testicular cancer accounts for 1% of male tumors. TesticuHowever, several studies showed that vasectomy was associated with testicular cancer,9 and prTherefore, we conducted this systematic review and meta-analysis to assess the association between vasectomy and risk of testicular cancer, aiming to provide further evidence and guidelines for the general public.A comprehensive electronic literature search of Pubmed, Embase, and Cochrane Library databases was conducted by two members to identify studies which assessed the association between vasectomy and the risk of testicular cancer. Separate searches were performed with the following search terms: (‘vasectomy’ or ‘deferentectomy’ or ‘vasoligation’ or ‘vasoligature’) AND (‘testicular neoplasms’ or ‘testicular cancer’). The detailed retrieval process is shown in We performed an initial screening based on the titles and abstracts. If uncertain, a subsequent full-text assessment was conducted. The second screening was a full-text review. Populations for this review and meta-analysis were broadly inclusive, involving any country and race. Studies were included if they met the following criteria: (i) the study design was a cohort, case-control study or randomized controlled trial; (ii) contained vasectomy and testicular cancer measures; (iii) studies that reported the odds ratio (OR) or relative risk (RR) relating vasectomy to testicular cancer outcome and the corresponding 95% confidence interval (CI) ; and (iv) the publication language was confined to English. Exclusion criteria were (i) duplicate literature; (ii) reviews, meeting summaries, and editorials comments; and (iii) studies that had no control group.Two researchers (Duan and Chen) independently extracted data from all eligible studies. Any differences were discussed or decided by the third reviewers (Deng). Data extraction was performed using a standardized data collection form. The following data were collected from each of the selected articles: the name of the first author, data source, study type, age, study period, publication year, length of follow-up, the number of patients and participants, OR, RR, 95% CIs and statistical adjustments for confounding factors.The Newcastle-Ottawa Scale (NOS) was applied to assess the quality of all studies. The NOS checklist contains three parameters of quality: (i) selected population, (ii) comparability of groups, and (iii) assessment of either the exposure or outcome of interest for case-control or cohort studies. Each study was assigned a score of 0–9. The studies scored greater than or equal to 7 were considered to be high quality articles.Q- and I2- statistic. If heterogeneity was not present , a fixed-effect model was used to calculate the combined OR values. Otherwise, a random-effect model was used. Subgroup analysis was performed according to the study design and country. All results in this analysis were considered as significant only with a two-tailed P < 0.05. Both the Begg’s test and the Egger’s test were performed using Stata 12.1  to determine whether publication bias existed.In the meta-analysis, RevMan analytical software package  was used to combine the extracted data. The pooled OR or RR and the corresponding 95% CIs were calculated to assess the relationship between vasectomy and risk of testicular cancer. Heterogeneity was assessed using the chi-square test based After screening the manuscripts, we included eight articles . The detailed retrieval process is shown in As shown in P = 0.28) based on eight studies in a fixed effects model with no significant heterogeneity   . One of P = 0.69) based on six case-control studies in a fixed effects model, without heterogeneity    . The poo = 0.03) P = 0.21), based on five USA studies in a fixed effects model without significant heterogeneity  (P = 0.88), based on three English studies in a fixed effects model with mild heterogeneity   . The poo = 0.19) .Both the Begg’s test and Egger’s test were conducted to assess publication bias, indicating no significant publication bias among all the included studies .1. To the best of our knowledge, this report presents the first systematic review and meta-analysis assessing the association between vasectomy and the risk of testicular cancer. A total of 11,141 participants in case-control studies and 908,927 in cohort studies  were included in our systematic review and meta-analysis. Our results showed that there was no significant association between vasectomy and the development of testicular cancer. Vasectomy, as a common method of permanent birth control, should not be forbidden unless there are more high quality papers reporting the positive association between vasectomy and testicular cancer. More studies are required to further explore the association between vasectomy and risk of testicular cancer.2. There were two studies reporting positive association between vasectomy and testicular cancer,9. Strad3. Several human immune system effects caused by vasectomy were reported in a number of studies. For example, 50% of the men with vasectomy were found to have circulating spermatozoal antibodies. The lev4. Potential bias was unavoidable. First, men who had a vasectomy were more proactive in seeking medical care if they sensed an abnormality in their bodies. Thus, t5. Our meta-analysis had several potential limitations. First, only British and American articles were included. This would limit the results of our research to other populations. Second, due to the limited data available in the original article, we could not perform more comprehensive and detailed subgroup analysis, such as subgroups based on the staging of testicular cancer, follow-up time, and age. Third, most of the included articles were not recent. More newly published studies are required.Our meta-analysis suggested that there is no association between vasectomy and the development of testicular cancer. More studies are required to further explore the association between vasectomy and the risk of testicular cancer.S1 File(DOC)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S1 Table(XLSX)Click here for additional data file.


IFNG, such as IFNG +874 T/A(rs2430561), may be related to tuberculosis susceptibility, but this association has not been consistently observed. We performed an updated meta-analysis to evaluate the association between the IFNG +874 T/A (rs2430561) polymorphism and tuberculosis susceptibility. PubMed and SinoMed databases were searched up to October 2016, and odds ratios (OR) and 95% confidence intervals (CI) were used to assess the association strength. Based on search criteria for manuscripts reporting tuberculosis susceptibility and its relationship with the IFNG +874 T/A(rs2430561)polymorphism, 42 case-control studies from 39 different articles were retrieved. Significantly positive, decreased, and protective associations were found between the IFNG +874 T/A(rs2430561)polymorphism and tuberculosis risk in five genetic models. Moreover, in the stratified subgroup analysis, a protective relationship was detected in four different ethnicities and sources of the control groups. Furthermore, the IFNG +874 T/A(rs2430561)polymorphism played an important role in protecting individuals from both pulmonary tuberculosis and extra-pulmonary tuberculosis. Our meta-analysis suggests that the IFNG +874 T/A(rs2430561)polymorphism is potentially associated with tuberculosis susceptibility and may be used as a predictive biomarker. Further studies with larger sample sizes and consideration of gene-environment interactions should be conducted to elucidate the role of IFNG +874 T/A(rs2430561) polymorphism in tuberculosis susceptibility.Interferon-γ  is an important cytokine involved in providing resistance to mycobacterial diseases. Common variants of  Mycobacterium tuberculosis (MTB). Data from the global tuberculosis report estimated a worldwide incidence of 8.7 million cases, most of which occurred in Asia and Africa [M. tuberculosis, but only 10% of the infected individuals eventually develop clinical TB, indicating that the host's genetic and other factors  may play essential and complex roles in determining susceptibility and progression to tuberculosis [Tuberculosis (TB) is a chronic infectious disease caused by d Africa . One-thirculosis –4. An inrculosis , 6.IFNG) is the most extensively studied gene regarding tuberculosis susceptibility. Human IFNG is located on chromosome 12 (12q14) and has four exons spanning approximately 6 kb. Interferon-γ (IFN-γ), which is encoded by IFNG and produced by T helper 1 (Th1) lymphocytes, is upregulated and secreted as a major cytokine to activate macrophages, and is critical for the control of M. tuberculosis infection [Currently, the gene encoding interferon-γ (nfection . Cases onfection .IFNG and protection against TB in Sicilia (P < 0.05) [IFNG [Lio et al. first noted a significant association between the +874A/T polymorphism (rs2430561) in  < 0.05) . The SNP5) [IFNG . The +875) [IFNG . The spe5) [IFNG , 13. As IFNG+874 T/A (rs2430561) polymorphism and the risk of developing TB. However, the data were inconsistent, partly because of differences in study populations and case ascertainment criteria, or small sample sizes with a high rate of false-positives and limited power of detecting modest associations. Considering the important role of IFNG+874 T/A (rs2430561) polymorphism in TB development, we studied all eligible case-control studies that included characteristics such as ethnicity of the patients, types of tuberculosis, and control sources.Many epidemiologic studies, including meta-analyses , 15, sugIFNG (one), IFNG receptor gene polymorphisms (fifteen), and other genes (three), and lacked case-control study (five). Finally, 39 different articles [IFNG+874 T/A (rs2430561) polymorphism and TB susceptibility were included in our meta-analysis . A similar trend was found in the control group  polymorphism in different genetic models. For example, for the additive model (TA vs. AA), odds ratios (OR) = 0.71, 95% confidence intervals (CI) = 0.63-0.80, P-value of heterogeneity test (Ph) = 1×10-6, and in the dominant model, OR = 0.68, 95% CI = 0.60-0.77, Ph = 1×10-6  polymorphism in the five genetic models. For example, for the additive model (TT vs. AA), OR = 0.60, 95% CI = 0.44-0.81, Ph = 1×10-6 for PTB, and OR = 0.45, 95% CI = 0.27-0.75, Ph = 0.007 for EPTB  and extra-pulmonary tuberculosis (EPTB) risks and A rs243051 polymorTo improve our study, finally we made stratified subgroup analyses according to genotyping methods and sample size. Some positive associations were also found in this section Table .P = 0.269 for Begg's test and t = −0.87, P = 0.389 for Egger's test  analysis, z = 1.11, NRAMP1, IFNG, NOS2A, MBL, VDR, and certain TLR-associated genes as important for susceptibility to TB and malaria, and the list has been growing ever since [To understand the pathogenesis of TB and better predict individual risk, it is important to identify the SNPs that affect the function of genes contributing to TB susceptibility. Genome-wide association studies (GWAS) allow genotyping of frequent genetic polymorphisms in the genome without assuming the genomic location of the causal variants. As most of the genome has been surveyed, GWAS eliminates the disadvantages associated with the single polymorphism or candidate gene approach where only a few polymorphisms are investigated . Howeverer since –57.IFNG+874 T/A (rs2430561) polymorphism and the risk of developing TB. Since then, other researchers have reproduced their work on IFNG in different populations and for two disparate types of TB. However, the results were confounding, even within populations. Meta-analysis provides a means for effectively increasing the size of the sample by pooling data from individual correlation studies, thus enhancing the statistical power of the analysis to estimate genetic effects [Lio et al.  were the effects . We usedIFNG polymorphism and TB risk. Our analysis involved about 8,574 individuals with TB and 9,011 controls. The main discovery of our study was that the T-allele of the IFNG+874 T/A (rs2430561) polymorphism showed a protective effect for TB susceptibility, which was consistent with the observation that the presence of the T-allele correlates with high IFN-γ expression and increased resistance to M. tuberculosis infection, whereas the A-allele correlates with low expression. The highlight of our article is that we classified TB into PTB and EPTB, which assisted in the analysis of effective target sites for different types of TB, and thereby, we provided a novel concept compared to the previously published meta-analyses [To the best of our knowledge, this is the first systematic meta-analysis exploring the associations between analyses , 15.IFNG polymorphisms and TB. Therefore, it is necessary to evaluate the roles of specific environmental factors and lifestyles in disease prognosis.Although considerable efforts and resources have been invested in examining the possible associations between IFN gene polymorphisms and TB risk, certain inherent limitations exist. First, although we collected all eligible studies, the sample sizes of these studies were not large enough to provide adequate statistical power to evaluate the association between this polymorphism and TB risk, particularly for certain ethnicities. Thus, not only was there an increased likelihood of type I/II error, but also a lack of sufficient statistical power to evaluate the association between these polymorphisms and tuberculosis risk. Second, because of the complex nature of the immune system and the polygenic nature of complex diseases, such as TB, it has become increasingly evident that gene-gene interactions play a far more important part in an individual's susceptibility to tuberculosis than single polymorphisms would on their own . Specifi+874 T/A (rs2430561) polymorphism was greater than 0.95, which suggested that the data was trustworthy.In spite of these drawbacks, our meta-analysis provided several advantages. First, a substantial number of cases and controls were pooled from different studies, which significantly increased the statistical power of the analysis. Second, no publication bias was found and the Newcastle-Ottawa Scale (NOS) scores of the included studies indicated high quality. Third, our study contained the highest number of individuals so far, which conferred increased statistical power and credibility. The power of this meta-analysis of +874 T/A (rs2430561) polymorphism in IFNG may be associated with the risk of developing TB. Further studies that consider additional gene-environment interactions and are based on larger sample sizes should be conducted to elucidate the role of IFNG polymorphisms in the etiology and clinical characteristics of TB development.In conclusion, our present meta-analysis suggests that the http://www.sinomed.ac.cn/) databases through October 2016, using the keywords “tuberculosis,” “TB,” “polymorphism,” and “IFN-gamma.” One hundred and fifty-two articles were retrieved, 39 of which satisfied our inclusion criteria. We also screened references of the retrieved articles and reviewed all articles via a manual search.We searched the PubMed and SinoMed (IFNG+874 T/A (rs2430561) polymorphism; (ii) be case-controlled, and (iii) contain all three kinds of genotypes  for cases and controls. Studies were excluded if they (i) included no control population; (ii) did not report genotype frequency data, and (iii) were duplicated publications.For inclusion, studies were required to (i) assess the association between TB risk and The NOS  was seleTwo authors independently extracted the data that complied with the selection criteria. These data included the first author's last name, year of publication, country of origin, ethnicity of the study population, TB type, genotypes of both the case and control groups, source of control, HWE/ MAF in both case and control groups, and genotyping method. Ethnicity was categorized as Caucasian, Asian, African, and mixed population. The control subgroups were population-based (PB) and hospital-based (HB). The TB type included PTB and EPTB. All included studies were classified as larger (both number of case and control ≥ 100 samples) and medium-sized studies. The NOS score was also shown in this section.+874 T/A (rs2430561) single nucleotide polymorphism (SNP) in IFNG and TB risk. The statistical significance of the OR was determined with the Z-test. The heterogeneity assumption among studies was evaluated using a χ2-based Q-test. A P-value of > 0.10 for the Q-test indicated a lack of heterogeneity among studies. If significant heterogeneity was detected, the DerSimonian-Laird random-effects model was used; otherwise, the Mantel-Haenszel fixed-effects model was chosen [IFNG+874 T/A (rs2430561) polymorphism and tuberculosis risk by testing the allelic effect (T vs. A), additive model (TT vs. AA and TA vs. AA), dominant model (T carriers vs. AA), recessive model (TT vs. A carriers), and overdominant model (TA vs. AA + TT). A sensitivity analysis was performed by successively omitting studies to assess the stability of the results. The departure of frequencies of the IFNG+874 T/A (rs2430561) polymorphism from the expected under HWE was assessed by Pearson's χ2 test, and P < 0.05 was considered significant [P-value < 0.05 was considered significant [http://www.power-analysis.com/.Based on the genotype frequencies for cases and controls, OR with 95% CI were used to measure the strength of the associations between the A rs24305 single ns chosen . We invenificant . Publicanificant . All staIFNG+874 T/A (rs2430561) SNP was conducted using methods described in the retrieved literature, such as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), polymerase chain reaction-amplification refractory mutation specific (PCR-ARMS), polymerase chain reaction-allele specific primers (PCR-ASP), polymerase chain reaction-sequence specific primer (PCR-SSP), polymerase chain reaction-allele-specific oligonucleotide (PCR-ASO), and amplification refractory mutation system-multi gene/multi primer polymerase chain reaction (ARMS-MG/MP-PCR).Genotyping of the


Whether hypothyroidism is an independent risk factor for cardiovascular events is still disputed. We aimed to assess the association between hypothyroidism and risks of cardiovascular events and mortality.We searched PubMed and Embase from inception to 29 February 2016. Cohort studies were included with no restriction of hypothyroid states. Priori main outcomes were ischemic heart disease (IHD), cardiac mortality, cardiovascular mortality, and all-cause mortality.Fifty-five cohort studies involving 1,898,314 participants were identified. Patients with hypothyroidism, compared with euthyroidism, experienced higher risks of IHD (relative risk (RR): 1.13; 95% confidence interval (CI): 1.01–1.26), myocardial infarction (MI) , cardiac mortality , and all-cause mortality ; subclinical hypothyroidism  was also associated with higher risks of IHD and cardiac mortality. Moreover, cardiac patients with hypothyroidism, compared with those with euthyroidism, experienced higher risks of cardiac mortality  and all-cause mortality .Hypothyroidism is a risk factor for IHD and cardiac mortality. Hypothyroidism is associated with higher risks of cardiac mortality and all-cause mortality compared with euthyroidism in the general public or in patients with cardiac disease.The online version of this article (doi:10.1186/s12916-017-0777-9) contains supplementary material, which is available to authorized users. Thyroid hormones have wide effects on the body and play an important role in homeostasis of the cardiovascular system . AbnormaWhether hypothyroidism  and overt hypothyroidism (OHypo) in this article), SCH or OHypo, is an independent risk factor for cardiovascular events or mortality has conflicting opinions. It is also conflicting whether adults with hypothyroidism and preexisting cardiovascular disease might be at particularly high cardiovascular risk –5. AlthoThis meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist  to measure thyroid function and follow persons prospectively; to assess ischemic heart disease (IHD), mortality or other cardiovascular events; and to provide risk estimates or sufficient data to calculate risk estimates associated with hypothyroidism compared with euthyroidism; (2) to be cohort studies published as original articles; and (3) to be independent. For multiple publications of the same study design, we included the estimates from the most recent or informative reports.Data were extracted by one reviewer (YN) and independently checked by another three reviewers ; the data included the first author’s name, publication year, location, female proportion, mean age, mean follow-up years, sample size, study design, study population, number of cardiovascular events and mortality, risk estimates, categories and definitions of hypothyroidism, thyroid treatment, and covariates adjusted for in the multivariable analyses. Primary authors were contacted by email if the study did not provide the data needed. We used the Newcastle-Ottawa scale to evaluate the quality of cohort studies. In the present analyses, we regarded a study awarded a total score of ≥6 as a high-quality study .Hypothyroidism was categorized as SCH and OHypo. Their definitions varied across studies. Generally, SCH was defined as elevated thyroid-stimulating hormone (TSH) levels and normal free tetraiodothyronine (FT4) levels. OHypo was defined as elevated TSH but decreased FT4 levels . In thisThe primary outcomes were IHD, cardiac mortality, cardiovascular mortality, and all-cause mortality as defined by International Classification of Diseases-10-CM (ICD-10-CM) diagnosis codes. For IHD (I20–I25), we included angina pectoris, myocardial infarction (MI), and chronic ischemic heart disease. For cardiac mortality, we included deaths caused by IHD, progressive heart failure (HF), arrhythmia, or cardiac arrest . For cardiovascular mortality, we included deaths from diseases of the circulatory system (I00–I99). We used both cardiac and cardiovascular mortality for the following two reasons: first, both of them had been discussed in different meta-analyses previously; second, the related data of both outcomes were available from considerable original cohort studies. Therefore, it is necessary to analyze both of them in one meta-analysis to achieve comprehensive comparison to the previous meta-analyses. The secondary outcomes were stroke, HF, MI, atrial fibrillation (AF), and total cardiovascular events.I2 statistic to assess heterogeneity among studies. The formula is {(Q-df)/Q × 100%}, where Q is the chi-squared statistic and df is its degrees of freedom [I2 < 50%, low heterogeneity; 50–75%, moderate heterogeneity; >75%, high heterogeneity [The available risk estimates that were extracted were mostly hazard ratios (HRs), while those in partial studies were rate ratios (RRs) –15, inci freedom . We use ogeneity , 27.n ≥ 10) [I2 ≥ 50% (moderate or high heterogeneity), we used the hetred command in Stata to evaluate the change in between-study heterogeneity as one or more outlier studies were excluded from the calculations, a method which was developed by Patsopoulos [Several predefined subgroup analyses were intended to explore potential sources of heterogeneity in primary outcomes (metan command); where enough studies (n ≥ 10)  were avan ≥ 10) , we intesopoulos . If avaiP < 0.05.If there were at least 10 studies included in each outcome of the meta-analysis, publication bias or small study bias was assessed with a funnel plot by using Egger’s regression asymmetry test (metabias6 command) , 32. StaOf 3889 reports identified, we excluded 3775 studies that were unrelated to our theme and 59 studies after detailed evaluation. Fifty-five cohort studies met the inclusion criteria. Figure Additional file Additional file Thirteen studies with 615,596 individuals and 16,862 events analyzed with IHD. Twelve studies’ risk estimates were adjusted for age, ten adjusted for sex, and more than half adjusted for smoking, BMI, hypertension, or diabetes, but only three adjusted for RT.I2: 40.2%; P = 0.066; Fig. P = 0.65; Additional file Overall, patients with hypothyroidism experienced a higher risk of IHD compared to euthyroidism , with evidence of low heterogeneity . Sensitivity analysis by hetred command in Stata found that two outlier studies might be the source of heterogeneity [I2: 37.9%; P = 0.17; Table Evidence synthesis for cardiac mortality showed a statistically strong association with hypothyroidism . In sensitivity analyses, the risk estimates did not change after analyzing with studies removing RT at baseline or with high-quality studies. No publication bias was found (Egger test: P = 0.92). In meta-regression and subgroup analyses, the pooled RRs of each group or subgroup were almost similar to the total.The summary RR of cardiovascular mortality associated with hypothyroidism was 1.11 . In subgroup and meta-regression analyses, we observed evidence for heterogeneity by study population (P = 0.009). The RR for all-cause mortality in convenience samples was significantly higher than that in population-based studies; also, the risk of all-cause mortality in cardiac patients with hypothyroidism was significantly higher than that in cardiac patients with euthyroidism . We observed that SCH was also associated with a higher risk of all-cause mortality .The pooled RR value of all-cause mortality was 1.25 . No publication bias was found (Egger test: P = 0.44).In sensitivity analyses, the pooled RR value changed little after inclusion of large cohorts, studies without RT at baseline, or high-quality studies. Sensitivity analyses by hetred command in Stata found eight outlier studies , 35–37. I2: 52.3%; P = 0.03). After excluding one outlier study [I2: 0.0%; P = 0.43).For stroke, nine studies were included, reporting 27,196 events among 761,993 participants. All studies adjusted for age, eight adjusted for sex, most adjusted for cardiovascular risk factors, and only one adjusted for RT. The overall RR of stroke was 1.09 . After excluding one outlier study [Of eight studies analyzed with HF, there were 23,033 events among 599,876 participants. Seven studies adjusted for age, all adjusted for sex, most adjusted for cardiovascular risk factors, and only two adjusted for RT. Evidence synthesis for HF did not show a significant association with hypothyroidism . The same results were obtained after using fixed-effect models, inclusion of large cohorts, studies without RT at baseline, or high-quality studies.Seven studies involving 588,182 participants were analyzed reporting a total of 13,263 MI. Six studies adjusted for age, four adjusted for sex, most adjusted for cardiovascular risk factors, and none adjusted for RT. Hypothyroidism was significantly associated with higher risk of MI . After excluding one outlier study [I2: 0.0%; P = 0.85), but the RR was still not statistically significant.For AF, four studies were included, reporting 18,259 events among 616,608 individuals. All studies adjusted for age and sex, most adjusted for cardiovascular risk factors, and only one adjusted for RT. The pooled RR value of AF was 1.02 . Similar results were observed in the sensitivity analyses.Eight studies involving 579,969 participants were analyzed reporting a total of 45,545 total cardiovascular events. Six studies adjusted for age, six adjusted for sex, most adjusted for cardiovascular risk factors, and none adjusted for RT. The pooled RR for total cardiovascular events was 1.16 (95% CI: 0.97–1.38; Fig. In this analysis of 1,898,314 participants from 55 cohort studies, hypothyroidism is associated with higher risks of IHD, MI, cardiac mortality, and all-cause mortality. These associations mostly persist in sensitivity analyses, indicating the stability of our results. In subgroup analyses, we also observe that SCH is significantly associated with higher risks of cardiac mortality Table  and IHD Our study is the first meta-analysis to evaluate risks of cardiovascular events and mortality in hypothyroidism with no restriction of hypothyroid states and study population. In subgroup analyses, our results are generally consistent with previous meta-analyses showing modest higher risks of IHD and cardiac mortality associated with SCH or SCH with TSH levels ≥10.0 mIU/L –9, 39. HPrevious meta-analyses show conflicting results of risk of all-cause mortality in SCH. Some –10, but However, our findings could not indicate that hypothyroidism is an independent risk factor. RT might be one of the important confounders, for only a small number of cohort studies adjusted for RT (Additional file We find no significant association between hypothyroidism and risks of stroke, HF, or AF. One previous IPD meta-analysis focused on risk of stroke in SCH . The autHigher risks of IHD, MI, and cardiac mortality with hypothyroidism might be associated with the known effects of thyroid hormone on the circulatory system. Altered endothelial function, increased atherosclerosis, and altered coagulability have been reported to be associated with hypothyroidism and may accelerate the development of IHD .A retrospective cohort study of patients from the United Kingdom General Practitioner Research Database found that levothyroxine therapy in SCH was associated with fewer IHD events in younger individuals . HoweverThe strengths of this meta-analysis include strict inclusion criteria, many more cohort studies included than ever before, and predefined sensitivity and subgroup analyses. There is no publication bias, which favors stability of the findings. Moreover, we do not restrict hypothyroid states and study population, thus realizing a full-scale assessment of the effects of hypothyroidism.There are some limitations. Firstly, heterogeneity is observed in some outcomes. However, we have found all sources of heterogeneity, and sensitivity analyses confirm the stability of our results. Secondly, the absence of IPD might influence the accuracy of the results. Thirdly, thyroid function testing was mostly performed at baseline, which would weaken the accuracy of the results regarding the possible change of thyroid function during follow-up. Another limitation is the different TSH values used across studies to define thyroid disease.Our analyses suggest that hypothyroidism or SCH is a risk factor for IHD and cardiac mortality. Moreover, hypothyroidism is associated with higher risks of cardiac mortality and all-cause mortality compared with euthyroidism in both the general public and cardiac patients. Our analyses offer more reliable evidence of higher risks of IHD events and mortality in patients with hypothyroidism, and highlight that cardiac patients with hypothyroidism should be considered seriously for higher risk of cardiac mortality and all-cause mortality. However, more high-quality prospective cohort studies and randomized controlled trials are needed to draw firmer conclusions.


SerCys+SerSer  genetic models. Sensitivity analyses showed the results were not robust, cumulative meta-analyses and trial sequential analysis indicated the results didn't not need more studies to identification. Subgroup analyses showed there was a significant association in Caucasian, laryngeal squamous cell carcinoma, studies agreement with Hardy-Weinberg equilibrium, and alcohol drinkers subgroups under the corresponding contrasts. In addition, the results of Egger’s test were contradictory.All eligible studies were searched from the online databases including PubMed, Web of Science, China Knowledge Resource Integrated Database, and Wanfang databases up to February 10, 2017. After study selection and data extraction, the meta-analysis was performed using STATA 12.0 software and TSA software version 0.9 Beta.hOGG1 Ser326Cys polymorphism may be associated with increased risk of HNSCC, especially in Caucasians, alcohol drinkers and the patients with laryngeal squamous cell carcinoma.Our meta-analysis results indicated that  Head and neck squamous cell carcinoma (HNSCC), involving the oral cavity, pharynx, and larynx, constitutes 12% of all malignant neoplasms worldwide –12. Of thOGG1) is a DNA glycosylase or AP lyase, which has been investigated to play a vital role in preventing carcinogenesis by repairing oxidative damage to DNA . TSA showed that the overall results might be conclusive, as their cumulative z-curves crossed both the conventional boundary and the trial sequential monitoring boundary providing firm evidence , alcohol drinkers and controls agreement with HWE under corresponding models. We did not find any significant association in other subgroups by control source, smokers, and genotyping method. Table p = 0.048), CysCys vs. SerSer (p = 0.04), and CysCys vs. (SerCys+SerSer) (p = 0.02) genetic models; however, the publication bias was not detected in the CysSer vs. SerSer (p = 0.15) and (CysCys+ CysSer) vs. SerSer (p = 0.14) genetic models.Funnel plots based on the trim and fill method indicated obvious publication bias Figure . Egger’shOGG1 Ser326Cys polymorphism might be associated with increased risk of HNSCC, and the TSA results also provided firm evidence. However, the results changed into nonsignificant after adjusting the publication bias by trim and fill method; sensitivity analysis and cumulative meta-analysis suggested the pooled ORs and corresponding 95%CIs were not robust. Minelli et al. [hOGG1 Ser326Cys polymorphism was significantly associated with LSCC. However, only four studies focused on LSCC, that might reduce the reliability of the results. As we know, smoking and alcohol consumption have been identified as major risks for HNSCC [hOGG1 Ser326Cys polymorphism and HNSCC in smokers and alcohol drinkers, respectively. Interestingly, we found no significant association between hOGG1 Ser326Cys polymorphism and HNSCC in smokers but statistically significant relationship in alcohol drinkers. By carefully reading relevant papers, we found that the smokers were not stratified by smoking magnitude; nevertheless, it’s known that the power of influence of heavy smoking must be different from that of occasionally smoking. These results suggest that when designing a case-control study of genetic polymorphism and the risk of cancer relating to other factors, such as smoking- or alcohol-related cancer, researchers should stratify the smokers and drinkers based on magnitude, for giving a more reliable conclusion.The present meta-analysis including 3,875 HNSCC cases and 4,696 controls indicated that i et al.  thought hOGG1 Ser326Cys polymorphism increased HNSCC risk under all comparisons. The meta-analysis from Wei et al [hOGG1 Ser326Cys polymorphism and HNSCC under CysCys vs. SerSer model. Our meta-analysis incorporated 13 studies, which showed that hOGG1 Ser326Cys polymorphism was associated with the elevated risk of HNSCC under CysCys vs. SerSer and CysCys vs. (CysSer + SerSer) contrasts. Moreover, we extracted the data of oral cavity, larynx, and nasopharynx cancers as well as the data of smokers and alcohol drinkers to performe relevant subgroup analyses. Relatively speaking, our paper was more scientific than previous studies on this topic, because it was the first one containing subgroup analyses based on the tumor sites, smokers, and alcohol drinkers. Third, we used cumulative meta-analysis and TSA to explore the results and found the relevant original studies didn’t need to be conducted continuously. Fourth, we assessed the methodological quality of included studies.Comparing with the previous meta-analyses , 24, ourMeta-analysis is a retrospective analysis ; therefohOGG1 Ser326Cys polymorphism may contribute to the occurrence of HNSCC, especially in Caucasians, alcohol drinkers and the patients with LSCC. However, due to the aforementioned limitations, the results of current meta-analysis should be treated with caution.In summary, our meta-analysis suggests that This meta-analysis was reported in accordance with the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guideline .hOGG1 Ser326Cys polymorphism and risk of HNSCC; (ii) the study design was a cohort or case-control study; and (iii) the data of genotype distributions in case and control groups were available. The language was restricted to English and Chinese.Each study included in the present meta-analysis was required to meet all the following criteria: (i) the study focused on the association between A comprehensive electronic search was performed in PubMed, Web of Science, CNKI  and Wanfang database up to February 10, 2017. The following search terms were used: (“human oxoguanine glycosylase 1” OR “hOGG1” OR “human 8-oxoguanine glycosylase 1”) AND  AND (“cancer” OR “carcinoma”) AND (“polymorphism” OR “variant”). We also conducted a manual search of references cited in include studies and previously meta-analyses , 45 for Two authors independently selected included studies and extracted essential data was extracted from all eligible studies, which contained surname of the first author, year of publication, country of study performed, ethnicity of descent, source control, HWE of control, tumor site, sample size, number of genotype distribution, genotyping method, and relevant methodological information. A cross-check over these data was performed by these two authors; any disagreements would be settled through discussion until reaching a final consensus.I2 value [2I < 25% indicating the homogeneity was good, the fixed effect model was used; otherwise, random-effects model was applied. The OR and its 95% CI were calculated to estimate the overall and subgroup results. Subgroup analysis was used to explore and explain the diversity of the results in different researches using the following factor as stratifying variables: ethnicity, tumor site, source of control, smokers, alcohol drinkers, agreement with HWE in control group, and genotyping method. TSA was performed using diversity-adjusted information size based on α = 0.05, β = 0.20 (power at 80%), information size with estimate, and case and control event proportion calculated from meta-analysis, through TSA software version 0.9 Beta [All the data analyses were applied using the STATA 12.0 software. HWE test of control group was performed by chi-square test. Heterogeneity among the included studies was tested by the I2 value . If I2 <0.9 Beta –40.The sensitivity analysis was conducted by deleting every included study each time to investigate the influence of overall results . The cum


N = 11762 participants) were included for this meta-analysis. Elevated neutrophils-to-lymphocytes ratio have a close relationship with the poor Overall Survival of colorectal cancer with the pooled HR being 1.92 . This meta-analysis indicated that elevated neutrophils-to-lymphocytes ratio, platelet-to-lymphocytes ratio or platelet counts may be a cost-effective and noninvasive serum biomarker for poor prognosis for patients with colorectal cancer.Recently, several studies have reported that inflammatory response and elevated platelet counts may be associated with the poor prognosis of colorectal cancer. This meta-analysis was designed to analyze and evaluate the prognostic role of elevated preoperative or pretreatment neutrophils-to-lymphocytes ratio, platelet-to-lymphocytes ratio or platelet counts in patients with colorectal cancer. We searched PubMed, EMBASE, Cochrane Library and Web of Science to April, 2016. A total of 23 studies ( The colorectal cancer (CRC) is one of the increasingly common malignancies worldwide. According to the report from GLOBOCAN 2012, the incidence rate of CRC is at the third place becoming one of the most common cancers . At presHopefully, in recent years, several reviews have reported that elevated platelet counts and NLR may be associated with the poor prognosis of gastric cancer, lung cancer, renal cancer and gynecologic malignancies –9. BesidN = 11762 participants) were included in this meta-analysis, of which 16 studies including 8691 participants were included for NLR . For the cut-off value of NLR equal to 5, the pooled HR in patients with elevated NLR was significant higher than patients with normal NLR   and prognosis, of which five studies including 956 participants were for OS and three studies  includin2I ≥ 50%, P ≤ 0.05), a random effect model was used to estimate the pooled HR. The combined HR indicated that elevated PLR had a statistically significant association with the OS of patients with colorectal cancer  , a fixed effect model was used to estimate the association between elevated PLT and OS. The pooled HR with no significant heterogeneity indicated that elevated PLT had an obvious association with overall survival   for OS, NLR  for DFS and PLR did not reveal any obvious evidence of asymmetry Figure . HoweverThe relation between inflammation and malignancies was identified in the 19th century by Rudolf Virchow . GrowingPlatelet plays an important role in the development and progression of malignancies as well. Great interest has been given in the prognostic role of thrombocytosis for patients with malignancies recently, as previously mentioned. However, the true mechanism or association between thrombocytosis and malignancies had not been clarified. There were several possible explanations for the association between elevated platelet counts and poor prognosis of malignancies. First, platelet might protect tumor cells from cytolysis, thereby promoting metastasis, by surface shielding them from immune system detection, and this seems to be the main mechanism of platelet protection . SecondlP = 0.03] for OS and 1.49  for DFS. By sensitivity analysis, we found that the study from Son, Z.Q 2014 had a significant impact for the results [P = 0.006] for OS and 1.93  for DFS. What is more, for the association between NLR  and OS, meta-analysis also showed no significant correlation, with the pooled HR being 1.19 . Likewise, when the study from He, Wen-zhuo. 2013 [P = 0.02]. Another cause of the results may be the small number patients or only a few studies for the analyses. The sensitivity analysis did not draw any different conclusions for other analyses in this meta-analysis.We perform this meta-analysis for purpose of demonstrating the indicative significance of NLR, PLR and elevated platelet counts for prognosis in patients with colorectal cancer. Our results statistically supported the conclusions that elevated NLR or PLT had a significant association with the poor prognosis in colorectal cancer, which was consist with the conclusions in gastric cancer, lung cancer and gynecologic malignancies , 7, 9. I results . When thuo. 2013  was reje9/L to 400 × 109/L. Based on the various discordance, we chose 5, 150 and 400 × 109/L as the cut-off value of NLR, PLR and PLT respectively with decreasing the number of studies included. The second limitation is the variation of the clinical stages, for that the prognosis of patients with cancer is associated with clinical stages. The majority of studies included showed no significant difference in clinical stages with the P value of Chi-squared test more than 0.05. But there were many studies had significant differences in clinical stages for NLR [P value less than 0.05. Besides, the incidence or significance of the association between different clinical stages and prognosis for PLT was also different. The incidence of thrombocytosis was associated with clinical stages and increased to 12.2% and 20.6% in patients with stage III and IV disease respectively [Nevertheless, there were several limitations for this meta-analysis. The main limitation is the inconsistency of the cut-off values of NLR, PLR and platelet counts. For NLR, some studies used the cut-off values with 4, 2.9, 2.8, and 2.6 and so on. For example, Shen, L.J  suggeste for NLR , 59, PLR for NLR , 29, 59 ectively . As 2014ectively . Moreoveectively . FinallyTaking the limitations above into account, further researches need to clear the association between elevated NLR, PLR and platelet counts and prognosis in patients with different clinical stages.Despite many difference and influencing factors, we could cautiously draw a conclusion that elevated NLR, PLR and platelet counts may have a close association with worse survival in colorectal cancer patients, with consideration of the evident statistical significance. Elevated NLR, PLR and platelet counts may be used as three prognostic indicators for early identification of CRC patients with worse prognosis, and then more attention and adjuvant therapy could be given to these patients.9/L), NLR  or PLR  were reported or can be obtained; (5) The outcomes including OS or DFS were reported; (6) Sufficient data (HR and 95%CI on OS or DFS) were provided.The including criteria of this meta-analysis were as follows: (1) All of randomized, controlled trials (RCTs), observational prospective or retrospective studies were included; (2) Included people with a diagnosis of colorectal cancer; (3) Included patients received operation or other adjuvant therapy; (4) Pretreatment platelet counts  Trials on animals; (2) Abstracts, letters, editorials, expert opinions, reviews, case reports; (3) Patients having other primary tumors; (4) Studies without sufficient data; (5) The cut-off value did not meet our including criteria.We searched PubMed, EMBASE, Cochrane Library and Web of Science to April, 2015. We also hand searched the citation lists of included studies and previously identified systematic reviews to identify further relevant trials. our searching terms and procedures were as follows: (1)“thrombocytosis”, “platelet count*”; (2) “neutrophil lymphocyte ratio”; “neutrophil to lymphocyte ratio”, NLR; (3) “platelet lymphocyte ratio”, “platelet to lymphocyte ratio”, PLR; (4) “colorectal cancer”, “rectal cancer”, “colonic cancer”; (5) “prognosis”, “survival”, “outcome”; (1 OR 2 OR 3) AND 4 AND 5. Other related terms, including references of some literatures we read, were also searched in English. Two assessors independently screened the titles and abstracts of each study. Once relevant studies became certain, the full texts were obtained for further evaluation.Two reviewers assessed the quality of all the included studies using the 9-star Newcastle-Ottawa Scale (NOS)  independData for the analysis were extracted independently by two reviewers, and disagreement was resolved by their discussion. In addition, the extracted contents including study demographics, published years, country, trial design, outcome and clinical stage were extracted using a standardized form.Data collected were input into RevMan 5.2 software for analysis .P value and 2I. 2I ≥ 50% or P ≤ 0.05 was deemed to represent significant heterogeneity [2 ≤ 50% and P ≥ 0.05), a fixed effects model was used. Finally, publication bias was assessed by Begg's and Egger's test. If the shape of funnel plots revealed no obvious evidence of asymmetry, we considered that there was no obvious publication bias. All statistical analyses were performed using standard statistical procedures provided in RevMan 5.2 [In this meta-analysis, the impact of NLR, PLR or PLT on patients’ prognosis was measured by estimating the Hazard Ratio (HR) between elevated NLR, PLR or PLT groups and normal NLR, PLR or PLT groups. The associated 95% confidence intervals (CI) were also measured. The heterogeneity between studies was evaluated with ogeneity , 74, andvMan 5.2 .


Stratified analysis revealed that tea, especially green tea, had a protective effect among female and rectal cancer patients. Particularly, the dose-response analysis showed that there was a significant inverse association between an increment of 1 cup/day of tea consumption and colorectal cancer risk in the subgroup of the green tea drinking  and female . Our findings indicate that tea consumption has an inverse impact on colorectal cancer risk, which may have significant public health implications in the prevention of colorectal cancer and further similar researches.It is well known that the tea extracts, mainly polyphenols as chemo-preventive elements, could act as cancer progression blockers. Although the association between tea consumption and colorectal cancer risk has been widely investigated, the results still remain inconsistent. We conducted a dose-response meta-analysis to evaluate their relationships by enrolling qualified 29 literatures. The summary odds ratio (OR) of colorectal cancer for the highest  Colorectal cancer (CRC) is one of the most common malignances occurred in the digestive system. Although the diagnosis and treatment of CRC have been improved in the last decades, the incidence of CRC presents an upward trend , more seEmerging evidences have demonstrated that dietary factors, including tea intake, could contribute to the prevention of CRC . Many stIn the last decades, many epidemiologic studies have evaluated the connection between tea consumption and CRC morbidity and mortality. Nevertheless, the findings have not reached a consensus currently. Some of the inconsistencies were contributed by the discrepancy in tea-drinking habits, types of tea source and the amount of consumption . BesidesIn this study, we performed a dose-response meta-analysis of cohort studies and case-control studies with the aims: (a) to estimate the association between tea consumption and CRC risk; (b) to examine the relevance degree of tea consumption and CRC risk according to study designs, study populations, genders, cancer subtypes, tea source and different degrees of adjustment for confounding factors; and (c) to evaluated the dose-response patterns of tea consumption on the risk of CRC.n = 1) or CRC risk (n = 4), no quantitative analysis on tea consumption (n = 12) and no odds ratios/relative risks (ORs/RRs) or 95% confidence internals (CIs) (n = 1). Three additional articles were included from the further reference review [Figure e review . Totallyrisk n = , no quane review , includivs. the lowest classes of tea consumption are shown in Figure P = 0.001, I2 = 43.4%), showing inversely relationship between tea drinking and CRC risk.The multivariable-adjusted ORs/RRs for each study were extracted and the combined ORs for the highest Subsequently, we performed stratified analysis to evaluate the relationship between tea consumption and CRC risk Table . When weP = 0.627, Figure Pnonlinear = 0.003) and female  without heterogeneity.A total of 10 studies including 5 cohort studies and 5 case-control studies, offering the number of cases and controls or person-years and ORs/RRs with 95% CI for at least 3 quantitative exposure levels, were enrolled for the dose-response meta-analysis. No significant evidence supported the association of an increase in tea consumption of 1 cup/day and CRC risk . Besides, the exclusion of another 9 studies not controlled for alcohol drinking revealed an OR of 0.87 . Furthermore, exclusion of any single study presented the similar overall results, with a range from 0.92 (95% CI = 0.86–0.98) to 0.95 (95% CI = 0.89–1.01).We designed a sensitivity analysis to investigate potential sources of heterogeneity. We excluded 9 studies without adjusted for smoking or passive smoking, and analyzed the rest studies. The result yielded a pooled OR = 0.94 (95% CI = 0.87–1.00) with marginal heterogeneity (2) was increased from 0.019 to 0.030 when we analyzed the influence of those five factors in the meta-regression. As shown in vs. lowest level of tea consumption and CRC risk with P = 0.070 of Egger test.The factors including study design, region, tea sources, gender and publish year were taken into consideration for meta-regression analysis, but none of them showed significant source of heterogeneity . The estIn recent years, the association of tea consumption and CRC development has been widely investigated, but the findings remain controversial. A cohort study performed in the United States suggested that there seemed no inverse association between tea consumption and CRC . In contIt is well known that CRC, as one of the major causes of mortality of death in the world, is mainly caused by genetic and environmental factors. Immigration epidemiological studies have reported that after the residents in low-incidence countries moved to high-incidence regions, the morbidity of colorectal cancer increased rapidly , which pMany studies, including animal and cell experiments, have revealed the anti-cancer effect of tea extracts on cancer development and progress , 40. RecThe latest meta-analysis on the relationship between tea consumption and CRC risk was reported by Wang et al. , which oIn the present study, we enrolled all available case-control studies and cohort studies, which involved CRC risk and tea consumption. In our study, only 46,467 participants were included in case–control studies, whereas 1,595,540 subjects in cohort studies. We know that the conclusion from cohort studies is considered preferable to that from case–control studies owning to their scientific and strict evidence. Additionally, more protective effects of tea consumption were identified in the subgroup of the Asians, green tea drinking and female. In the further dose-response analysis, we identified a significant association without heterogeneity between an increment of 1 cup/day of tea consumption and colorectal cancer risk in the subgroup of the female population. These findings were mainly on account of the increasing tea consumption and healthier lifestyle in the female worldwide . Considen = 29), whose data was substantial and significantly increased the statistical power of the analysis. Besides, a significant dose-response association between tea consumption level and CRC risk further strengthened the association. However, our study still has several limitations. First, heterogeneity cannot be fully eliminated, neither in overall nor in subgroups analysis. This might be for the different range of the highest and the lowest categories for tea consumption among enrolled studies. Second, the methods of calculating the tea consumption were different among all studies. Though we converted the amount of tea consumption to cups/day before performing the analysis, there still might remain some bias, resulting in the deviation of risk estimate values and confounding factors. Third, several studies only provided one or two reports while some included almost 6 reports. The bias of the quality and quantity of cases in included reports could influence the final results. Fourth, most of the included studies only displayed the results without providing the detailed calculation methods or the raw data  which may cause bias in results of the dose-response analysis. Fifth, the analysis methods and software and the limitation of our knowledge may account for the statistical bias. Above all, these results should be considered with caution.A strength of this study was that we enrolled all relevant studies  searched and retrieved potential studies. Our research was designed, conducted and reported according to the standards of quality for reporting mate-analyses.vs. non/lowest level of tea consumption. For those on which a dose-response analysis can be conducted, we resolved all disagreements by consensus.Studies were selected for meta-analysis have to achieve the following criteria: (a) designed by case-control or cohort study; (b) evaluated the associations between tea consumption and CRC risk; (c) all CRC cases were either histopathologically or cytologically confirmed; (d) provided the quantity of CRC cases and controls or person-years; (e) supplied relative risks (RRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs), especially for highest vs. lowest intake and 95% CIs and adjustment confounding variables. The evaluation system based on the Newcastle-Ottawa Scale was used to evaluate the study quality [The data extraction was conducted by two reviewers (Y.C. and M.D.) referring to the MOOSE  guidelines , and dis quality  by two iP < 0.05 was considered significant. The summary ORs were calculated by pooling RRs or ORs for highest vs. lowest categories of tea consumption from each study. The method designed by Greenland and Longnecker [2 test and I2 statistics, and the I2 statistic from 0 to 30% was considered as no or marginal heterogeneity, 30–75% as moderate heterogeneity and over 75% as significant heterogeneity [2) and its percentage were used to measure the heterogeneity degree and the extent of the explained heterogeneity of the characteristics, respectively. we removed one study once a time and conducted a sensitive analysis for the rest. Begg's funnel plots and the Egger's test were used to evaluate the publication bias with the significant set to P < 0.10 [All analyses were conducted by Stata version 11.0 . All statistical tests were two-sided, and a ngnecker  and Orsingnecker  (generalngnecker , 1 timesngnecker . The posogeneity . The fixogeneity . We furtP < 0.10 , 58.


EGFR-mutations and ALK-rearrangements. Oncology-wide gene pathway analysis revealed an association between contrast enhancement (imaging) and the targetable VEGF-signalling pathway. Although the need of independent validation remains a concern, radiogenomic biomarkers showed potential for prognosis prediction and targeted treatment selection. Quantitative imaging enhanced the potential of multiparametric radiogenomic models. A wealth of data has been compiled for guiding future research towards robust non-invasive genomic profiling.With targeted treatments playing an increasing role in oncology, the need arises for fast non-invasive genotyping in clinical practice. Radiogenomics is a rapidly evolving field of research aimed at identifying imaging biomarkers useful for non-invasive genotyping. Radiogenomic genotyping has the advantage that it can capture tumor heterogeneity, can be performed repeatedly for treatment monitoring, and can be performed in malignancies for which biopsy is not available. In this systematic review of 187 included articles, we compiled a database of radiogenomic associations and unraveled networks of imaging groups and gene pathways oncology-wide. Results indicated that ill-defined tumor margins and tumor heterogeneity can potentially be used as imaging biomarkers for 1p/19q codeletion in glioma, relevant for prognosis and disease profiling. In non-small cell lung cancer, FDG-PET uptake and CT-ground-glass-opacity features were associated with treatment-informing traits including  Considerable progress had been made in developing targeted therapies for genomic subtypes in cancer, but patient selection for these therapies can be challenging. Radiogenomics (sometimes imaging genomics) is a new, rapidly evolving field of research aimed at developing tools for non-invasive genotyping by identifying imaging biomarkers for genomic subtypes –3. RadioRadiogenomics yields considerable advantages for genotyping. Firstly, tumor genetic heterogeneity can be captured using radiogenomics. Biopsy-based genotyping in the clinical setting is generally confined to a single sample, although multiregional genotyping has been performed effectively to capture tumor heterogeneity –6. Radion = 79, 42%), non-small cell lung cancer (NSCLC) , and breast cancer . Often, studies used multiple modalities; 105 studies used MRI (56%), 80 CT (43%), 44 FDG-PET (24%), and 5 mammography (3%). In 59/187(32%) articles biological clarifications for imaging-genomics relations were identified. The 2440 identified radiogenomic associations in the database are presented as a pivot table, which provides an easy graphical interface to perform data queries using Microsoft Excel (2010/2013) (We included 187 articles published between July 2004 and February 2017. A PRISMA flow diagram for the inclusion process is available in the 10/2013) . Study cIDH mutation and 1p/19q codeletion, both associated with a more favourable prognosis .–35.IDH mn status –52 in gl studies , 44–47. fication , and EGFblastoma , 55 and roglioma  and gradroglioma .EGFR-mutation  and imaging . FDG-PET uptake was both negatively [EGFR-mutated tumors were on average more solid (less GGO) [ALK-rearranged tumors (treatable with ALK-inhibitors) were more solid in two [ALK-rearrangements from EGFR-mutations, ALK-rearranged tumors were more solid [ALK-wt, ALK-rearranged tumors had more spiculated [KRAS, which is the most frequent driver mutation, but no CT or PET features were repeatedly associated with KRAS-mutation status  , 85, altess GGO) –88. Howeess GGO) , 89–95. d in two  out of fd in two  studies n status .EGFR-mutation (multiple comparisons) [ALK or ROS1/RET fusions  [Recent studies performed multiparametric modelling and quantitative imaging in NSCLC –104. Indarisons) , 104, asarisons) , or combarisons) . Quantit = 0.70) . For dev = 0.70) . Additio = 0.70) . Similar = 0.70) , 101.BRCA-mutations with sharp margins and rim enhancement on MRI [This review only included studies with analyses on a genomic level; imaging-receptor associations based on immunohistochemistry analysis were reviewed elsewhere . High FDt on MRI , but theRadiogenomic imaging models were used in breast cancer in twelve studies –121. FivKRAS-mutated tumors in five [KRAS-mutations could be predicted in a multiparametric model using high FDG-PET uptake in addition to CT texture and perfusion features [KRAS- and TP53-mutated also showed a higher SUVmax [KRAS- or BRAF–mutated” [Nine studies were included for CRC –135. Hig in five , 137 out in five  studies.r SUVmax , as did mutated” .BAP1-mutations, associated with invasive disease [p = 0.09 [p < 0.001 [Eight studies were included for RCC –145. BAP disease , 147, shp = 0.09 ; p < 0.0 < 0.001 ). A radi < 0.001 , 143. OnVEGF-expression [Three studies were included for HCC –150. Tumpression  was relapression . A gene pression . A diffeSDHx-mutated tumors [SHDx and VHL-mutated tumors [EGFR-expression was related to CT invasion, mass effect, size/volume [In paraganglioma, four studies found higher PET SUV-values for d tumors –154 or Sd tumors , relevane/volume  and lowee/volume . Additiop < 0.0001) and PI3K-Akt (p < 0.0001) , MAPK (p = 0.0004) signalling, Focal adhesion (p < 0.0001) and Apoptosis (p = 0.0069). Necrosis was associated with PI3K-Akt signalling (p = 0.0005) , Wnt signalling (p = 0.0054), and p53 signalling (p = 0.0348). Furthermore, necrosis was significantly associated with Cell cycle (p < 0.0001) and Focal adhesion (p = 0.0470).Looking at the molecular pathway-level, gene ontology analysis reveals associations between imaging groups and gene pathways in cancer (KEGG) oncology-wide Table . DistincN = 14) comprised features  of both MRI and CT in various malignancies. Results included the correlations of enhancement features with VEGF-expression in brain tumors (glioblastoma) [lastoma)  and headlastoma) .This study provided a comprehensive database of imaging-genomics associations, in which queries can be made . This reIDH1-mutation status and 1p/19q codeletion [IDH-wild type, IDH-1/2 mutated glioma have a favourable prognosis [IDH-status is the top-level diagnostic stratification after histology in the WHO index 2016 [IDH-status, the majority of findings were not independently validated. MR-perfusion [IDH-status in multiple studies and yield potential for future imaging-based IDH-mutation detection. The oncometabolite 2-HG is elevated in IDH-mutated cases and can be depicted using MR-spectroscopy [MGMT-methylated glioblastoma respond better to DNA alkylating chemotherapy with improved prognosis [MGMT-methylated cases showed higher ADC-values on DWI-MRI [EGFR aberrations were often correlated with MR-perfusion parameters, possibly due to the effect of EGFR on cell invasiveness and angiogenesis. However, despite the important role of EGFR in glioma development [EGFR- targeted therapies for glioma have not been developed [The 2016 WHO classification for diffuse glioma in adults is largely based on deletion . Howeverrognosis –23, 160.dex 2016 . Althougerfusion , 28 and erfusion , 31, 161troscopy , 162–164troscopy . The codtroscopy –26, 159.troscopy –39 with troscopy –39. Thisrognosis , 42. The DWI-MRI , 44–47 m DWI-MRI , 167. EGelopment , suitableveloped . To ensueveloped , 171. Poeveloped , 171. AlEGFR-mutated [ALK-rearranged [EGFR-mutations, which may be biologically explained by the activating role of mutated EGFR glycolysis through AKT-signalling [EGFR-mutated tumors; one of these validated their results in an independent cohort [EGFR-mutated cases were possibly unreliable because lower uptake was either not confirmed in multivariate analysis [KRAS-cases [EGFR-mutated tumors have a small component GGO, and ALK-rearranged tumors are the most solid. However, validation studies with standardised GGO measurements are needed to reliably discriminate genotypes. Similarly, standardised tumor morphology features need to be assessed in order to validate the predictive value of ill-defined tumor borders for ALK-status. Multiparametric (quantitative imaging) studies can be powerful for predicting individual genetic traits, as well as gene clusters related to prognosis. However, findings need to be validated in independent cohorts before they can be used in clinical practice.Since specific therapies are available for genomic subgroups of NSCLC, genotyping is important for directing therapy . However-mutated , 175 andarranged , 177 tumgnalling , 179. Tht cohort . The thranalysis , found iIn breast cancer, most radiogenomic associations were not independently validated. Limited results indicate FDG-PET can possibly discriminate molecular subtypes , 107. GeKRAS-mutation indicates irresponsiveness to EGFR-targeted treatment [EGFR-treatment decision making in CRC. In renal cell carcinoma, the amount of calcifications shows potential for predicting BAP1-status, which could be useful for assessing stage, grade and invasiveness [VEGF-targeted and doxorubicin treatment) as well as prognosis prediction. Microscopic venous invasion, a sign of poor prognosis and high recurrence risk, was associated with small intratumoral arteries (CT), which was independently validated [In colorectal carcinoma, reatment , 181 andreatment  and a rereatment  might bereatment . Althougsiveness , 147. Hosiveness , 145. Foalidated . Howeveralidated . The amoVEGF-expression, identified in brain and head neck cancers. The same association was found in a study (not included) assessing radiogenetics using immunohistochemistry in HCC [VEGF and EGFR genes were compared with angiogenesis related imaging features such as perfusion and contrast enhancement. Similarly in gene pathway analysis, angiogenesis (biology) may be the link between enhancement (imaging) and VEGF-pathway-signalling (genomics).Repeatedly found imaging-genomics associations show patterns among different neoplasms. A convincing relation was found for enhancement on imaging and y in HCC . For a my in HCC , 67, 158y in HCC , 185, bry in HCC , 126, ory in HCC , and RCCy in HCC . AngiogeVEGF gene, enhancement may be associated with the VEGF signalling pathway due to its regulating role in angiogenesis. Imaging biomarkers for the VEGF pathway may have clinical implications as they could aid patient selection for VEGF-targeted treatment. VEGF-targeted therapy has been shown to be effective in various cancer types, including CRC, NSCLC, and breast cancer [The importance of targeting multiple regulators in cancer pathways instead of single genes, is increasingly recognized. Genes associated with enhancement were enriched for the VEGF-signalling pathway. Similar to the association between contrast enhancement and the t cancer , 187.Gene pathway analysis results indicated furthermore that contrast enhancement and necrosis detected with imaging reflect MAPK- and PI3K-Akt-mTOR-activity. Similarly, this could again aid patient selection in the future for MAPK- and PI3K-AKT-mTOR pathways-based targeted therapies –190. An Although evidently standardised imaging features and genetic tests are needed for further validation, results of this gene pathway analysis do reveal that oncology-wide associations between imaging groups and oncology pathways with potentially clinical value may exist. Our findings do not only indicate radiophenotype-genotype associations could be similar in different cancer types, but also imply that radiogenomics could aid patient selection and monitoring of pathway-targeted treatment in the future.Different approaches were seen for conducting radiogenomics analysis. A considerable disadvantage of qualitative imaging assessment is the poor interobserver agreement. A powerful tool to overcome this is a validated feature set, such as VASARI  for gliop-values could not be incorporated in the database.A limitation of this study was the marked heterogeneity of genomic and imaging features and the variety of analysing methods which made data integration challenging. Another constraint was that the effect size and the direction of associations were not always reported. There might have been publication bias for significant findings, but the novelty of this field of research reduces this risk. A limitation was that data of included multiparametric modelling studies were usually not published online, so these Radiogenomic genotyping has the advantage that it can capture tumor heterogeneity, can be performed repeatedly for treatment monitoring, and can be performed in malignancies for which biopsy is not available. Moreover, radiogenomics is cost-effective using routine clinical imaging for analysis. The gene pathway analysis in this study revealed imaging-genomic networks in oncology and indicated that radiogenomics may be suitable for predicting efficacy of pathway-targeted therapies. Although an extensive amount of potentially valuable radiogenomic biomarkers was identified, validation studies are needed since the robustness of features obtained by different scanners remains an important concern. This study provides an extensive database of imaging-genomic associations that can guide future research to developing radiogenomic tools for treatment selection and prognosis prediction in human oncology. Radiogenomics, connecting multiparametric quantitative imaging with genomic data, yields great potential for non-invasive genotyping, thereby contributing to the shift towards precision medicine in oncology.We performed this study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement .We systematically searched the Medline and Embase databases for English literature published until 1-2-2017 on radiogenomics in oncology with search terms referring to radiogenomics and oncology . Referenp-values for associations and effect measures were incorporated in a database ) was used for gene pathway analysis based on functional annotation, calculating p-values using the hypergeometric probability mass function. method. P-values were corrected for multiple testing using the Bonferroni method .Gene pathway analysis was performed to examine concordance between grouped radiophenotypes oncology-wide and gene pathways. For this analysis, imaging features were classified for 14 coherent imaging groups. Significant radiogenomic associations for each imaging group were selected. Only single genes were selected (e.g. no chromosome-type aberrations), and the genes were annotated according to the HUGO Gene Nomenclature Committee (HGNC) nomenclature, regardless of neoplasm location or type of genetic information , methylation status). A minimum of 20 genes per imaging feature group was required for inclusion in the analysis. Gene pathway analysis was performed by comparing significantly associated genes within a particular imaging group with already existing functional gene pathway annotations; the cancer gene pathways in the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database , 199. Th


NLRP1) gene. We initially identified 1,306 candidate articles through literature searches of Pubmed, WOS, Embase, CNKI, WANFANGI, Ovid, Scopus, and Cochrane in July 2017. After strict screening, we included 19 eligible case-control studies, and analyzed the data using Stata/SE 12.0 software. No difference between vitiligo cases and controls was detected for NLRP1 rs12150220, rs2670660, or rs6502867 under most genetic models . No relationships were observed for other polymorphisms, including rs2670660, rs6502867, and the “A-A, G-T, G-A, A-T” haplotypes of rs2670660/rs12150220 (Passociation > 0.05). This meta-analysis demonstrates that within the Caucasian population, the NLRP1 rs12150220 polymorphism may correlate with a decreased risk of vitiligo-associated autoimmune diseases, especially autoimmune Addison's disease, type 1 diabetes, or systemic lupus erythematosus.Genetic variants are linked to vitiligo and associated autoimmune diseases. We performed a meta-analysis to evaluate the effects of the rs12150220, rs2670660, and rs6502867 polymorphisms within the human NLR Family Pyrin Domain Containing 1 ( NLRP1 gene on chromosome 17p13.2, which is also named NALP1  [NLRP1 gene and the risks of vitiligo or associated autoimmune diseases via meta-analysis. The possible role of s2670660/rs12150220 haplotypes was also analyzed.Vitiligo is a complicated autoimmune disorder characterized by skin depigmentation from progressively abnormal melanocytes , 2. Therotein 1) –12. NLRPotein 1) , and somotein 1) . Here, wn = 97), Web of Science , ExcerptaMedica Database , China National Knowledge Infrastructure , WANFANG (n = 32), Ovid (n = 345), Scopus (n = 474), and Cochrane (n = 5). 459 duplicate articles were then removed. 820 articles were excluded after further screening. As indicated in PRISMA-based flow chart of Figure n = 59), pigs (n = 1), rabbits (n = 1), rats (n = 3), mice (n = 45), Toxoplasma gondii (n = 2) were excluded as well. Then, eight articles were excluded for the reasons of non-SNP (n = 4), family data (n = 3) or lack of case-control data (n = 1). Nineteen eligible case-control studies were included in our final meta-analysis [We performed our meta-analyses in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)  and strianalysis , 17–33. NLRP1 polymorphisms and vitiligo risk, 563 cases and 1,351 controls from three Asian case-control studies underwent Mantel-Haenszel analysis of rs12150220. No between-study heterogeneities in any genetic models  led us to utilize fixed-effects model , AT+TT vs. AA , but not other models , compared with control group.To study the association between rs12150220, rs2670660, and rs6502867 PHWE > 0.05 (Table Passociation > 0.05), based on random-effect model (Table Pheterogeneity < 0.1 and I2 > 50%). For rs6502867, the fixed-effects model was applied for CC vs. TT+TC (Table Pheterogeneity = 0.170 and I2 = 37.7%), and random-effects model was applied for others . An increased vitiligo risk was only observed in CC vs. TT+TC models , but not any other model . Begg's test and Egger's test further excluded potential large publication bias . All these results failed to provide strong evidence regarding an association between NLRP1 rs12150220, rs2670660, rs6502867, and vitiligo risk.Five case-control studies containing 719 cases and 1,534 controls were included for the rs2670660 meta-analysis. Negative results were observed in the overall and subgroup analysis of Asian, NLRP1 rs12150220 and vitiligo-associated autoimmune diseases risk. A fixed-effects model was used for the models of AT vs. AA (Pheterogeneity = 0.213 and I2 = 19.8%) and carrier T vs. A (Pheterogeneity = 0.828 and I2 = 0.0%), whereas random-effects model was applied for others . Pooled analysis indicated a decreased risk of case group in the models of T vs. A , TT vs. AA , AT vs. AA , AT+TT vs. AA , TT vs. AA+AT , and carrier T vs. A  .As shown in Table Passociation < 0.05, OR > 1), but not TT vs. AA+AT (Passociation = 0.265), and carrier T vs. A (Passociation = 0.130). We detected a decreased SLE risk under all genetic models , but not the model of TT vs. AA+AT (Passociation = 0.201) or carrier T vs. A (Passociation = 0.122). A similar difference was detected in the ADD or TID case and control group under most of the genetic models . Potential large publication was excluded by our Begg's test and Egger's test . Sensitivity analysis data  and carrier G vs. A (Pheterogeneity = 0.514 and I2 = 0.0%), and random-effects model was used for others . No difference was observed in the case and control groups for the overall meta-analysis and stratification analysis under most of genetic models (Passociation > 0.05). A slight publication bias was found in the models of AG vs. AA  and AG+GG vs. AA , but not others . Similar results were observed in the rs6502867 meta-analysis , and a random-effects model was used for all others  . Thus, NLRP1 rs2670660/rs12150220 haplotypes are unlikely to be related to vitiligo-associated autoimmune diseases risks.Finally, we measured the association between > 50.0%) . Mantel-NLRP1 SNPs  with vitiligo risk [NLRP1 SNPs and vitiligo susceptibility, as well as vitiligo-associated autoimmune diseases.Incongruent conclusions have been reported for the associations of three igo risk , 20, 30.igo risk , 31, 32.NLRP1 variation in the risks of vitiligo and vitiligo-associated autoimmune diseases by systematically identifying all available relevant case-control studies. Literature was compiled from eight online databases: Pubmed, WOS, Embase, CNKI, WANFANGI, Ovid, Scopus, and Cochrane, with no publication date limitation. During the literature searches of Pubmed, WOS, Embase, CNKI, WANFANGI, and Cochrane, we sensed that less than 300 potential articles were acquired in each database, when using the search terms about “NLRP1” and “SNP”. For example, only 97 potential articles on the association between NLRP1 polymorphisms and clinical diseases were retrieved from the database of Pubmed. Considering these limited literatures, and naming complexity of the vitiligo-associated autoimmune diseases, we thoroughly checked these original articles one by one, in order to prevent the possible filtration of targeting articles during the advanced search using more terms. Only three common polymorphic variants were selected, including rs12150220, rs2670660, and rs6502867. We found that most participants in the included case-control studies of vitiligo were enrolled from Asian regions, but that most data were published in English.We focused on the potential role of NLRP1 rs12150220, rs2670660, and rs6502867 genotypes and the risks of vitiligo in the overall population. We found that the major A allele of rs12150220 was positively correlated with high risk to vitiligo-associated autoimmune diseases, including autoimmune Addison's disease, type 1 diabetes, and systemic lupus erythematosus. This suggests the rare T allele may serve as a protective factor against those diseases. The rs12150220 polymorphism may attenuate abnormal NLRP1 protein activity or the related inflammation/apoptosis process in the pathogenesis of vitiligo-associated autoimmune diseases. In addition, we observed a negative association for the rs2670660, rs6502867, and “A-A, G-T, G-A, A-T” haplotypes of s2670660/rs12150220.Our data did not provide evidence of an association between the NLRP1 rs12150220 and vitiligo in the Asian population was performed on just three case-control studies from two articles [With all meta-analyses, limitations regarding sample size, SNP selection, disease features, and heterogeneity origins need acknowledged. There were limited case-control studies available for inclusion. For instance, meta-analysis of the association between articles , 20. Subarticles . AlthougNot all patients included in the study presented with both vitiligo and a vitiligo-associated autoimmune disease. More data of cases suffering from both vitiligo and associated autoimmune diseases are required for more confident conclusions. Moreover, not all the other vitiligo-associated autoimmune diseases were analyzed. Some other vitiligo-associated autoimmune diseases, such as psoriasis, pernicious anemia and alopecia areata, were not investigated, owing to a lack of published case-control studies.We observed high between-study heterogeneities when analyzing rs2670660 and rs6502867 in vitiligo under most genetic models. Subgroup data showed that ethnicity or HWE may not contribute to heterogeneity, and sensitivity analysis also failed to reveal a source for the heterogeneities (data not shown). In addition, there were high heterogeneities among studies of the association between rs2670660, rs6502867, and vitiligo-associated autoimmune diseases under the allele, homozygote, dominant, and recessive models. However, the relative low probability of heterogeneities exists in disease-based subgroup analysis, suggesting the complexity of different specific disease types is the possible cause of heterogeneity. In addition, we observe an increased risk trend for the autoimmune thyroid disease patients with the minor allele. The differences of etiology and clinical characteristics of vitiligo-associated autoimmune diseases should be fully considered. Unavailable data factors such as different genotyping assays, diagnostic criteria, or clinical features may also contribute to high between-study heterogeneity.NLRP1 rs12150220 polymorphism and a decreased susceptibility to autoimmune diseases, especially autoimmune Addison's disease, type 1 diabetes, or systemic lupus erythematosus. These autoimmune diseases were all tightly associated with vitiligo. However, we did not observe a strong association between NLRP1 rs12150220, rs2670660, or rs6502867 and vitiligo risk, according to the currently very limited data. Similarly, rs2670660 and rs6502867 polymorphisms and rs2670660/rs12150220 haplotypes  within NLRP1 appear to have no effect on the risk of vitiligo-associated autoimmune diseases. Given the fact of insufficient statistical power as stated above, more data was needed to confirm these statements, and further determine the role of NLRP1 SNPs in the presence of vitiligo, or vitiligo together with autoimmune diseases.In sum, we identified a potential genetic relationship in the Caucasian population between the Pubmed, WOS, Embase, CNKI, WANFANGI, Ovid, Scopus, and Cochrane, were utilized for identifying candidate literature up to July 2017. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Only high-quality studies (NOS > 5) were included in our meta-analysis [Before statistical analysis, the quality of all these case-control studies was evaluated by the Newcastle-Ottawa scale (NOS) system, which is available at analysis , 35. TheP value of association (Passociation), OR (odds ratio), and 95% CI , Mantel-Haenszel analysis was performed on basis of six genetic models, namely allele , homozygote , heterozygote , dominant , recessive , or carrier  models. Passociation < 0.05 indicates correlation, and pooled OR > 1 suggests T allele of rs12150220 A/T, G allele of rs2670660 A/G, or C allele of rs6502867 T/C may act as a risk factor.To calculate the two-tailed 2 test. When Pheterogeneity value of Cochrane's Q statistic > 0.1 and I2 values < 50.0% at the same time, heterogeneity across studies was excluded, and a fixed-effects model was used. Otherwise, a random-effects model was utilized. Subgroup analyses of specific disease type, ethnicity, or HWE, and leave-one-out sensitivity analyses were then performed. A symmetrical funnel plot, PBegg > 0.05 and PEgger > 0.05 ruled out publication bias. We performed chi-square test to measure the Hardy-Weinberg equilibrium of control group. All analysis was performed with STATA12.0 .We assessed heterogeneity across case-control studies through both Cochrane's Q statistic and I


The colorectal neoplasm is the fourth most common malignancy among males and the third among females. In the Western world is estimated that 5% of the population will develop it, making this disease a major public health problem. . To analyze the prevalence of the polymorphism -765G / C region of the COX-2 gene in colorectal cancer patients compared to a control group, analyzing the possible association between this polymorphism and susceptibility to colorectal cancer This is a case-control study with 85 participants. Were selected 25 with colorectal cancer (case group) and 60 participants without colorectal neoplasia (control group). The molecular genetic analysis was perform to identify the polymorphism -765G / C COX2 gene with standard literature technique. In addition, patient’s clinical and pathological data were analyzed.  There was a light increase in prevalence between men in the case group, although this difference was not statistically significant. The results showed a high prevalence of GC and CC genotype in individuals with colorectal cancer, demonstrating an association between the presence of the polymorphism in the COX2 gene and susceptibility to colorectal cancer in this pattern (p=0.02). Similarly, there was also difference in allele frequencies in the groups. When patients with cancer were separated by tumor location, there was a higher prevalence of polymorphism in the left colon (p=0.02).  The polymorphism in the COX2 gene is associated with increased susceptibility to colorectal cancer, specially rectosigmoid tumors. The colorectal neoplasm is one of the most common malignancies diseases in the world, being the fourth among male and the third in female, revealing to be an important public health problemIt is believed that prostaglandins are involved in the genesis of CRC. Prostaglandins are small molecules derived from arachidonic acid, which are produced from the enzyme cyclooxygenase (COX). This enzyme is subdivided into COX-1, responsible for physiological activities and therefore is called constitutive, and COX-2 expressed after stimulation of cytokines, growth factor and mitogensIn physiological conditions, COX-2 is expressed in tissue of the gastrointestinal tract at very low levels. However, there is an increase of its expression in CRC, The changes in the COX-2 gene may imply changes in enzyme function and contribute to the inflammatory response or to the increase risk of developing CRCIn this context, the present study aims to estimate the allele and genotype frequencies of the COX-2 gene polymorphism, in order to evaluate the possible association between these frequencies and the susceptibility to CRC.This study was reviewed and approved by the Research Ethics Committee (Protocol no. 884/397) of the Institution. This was a case-control study, conducted in partnership with the Institute of Cancer of Londrina. All patients were previously informed about the objectives and procedures to be performed and had signed the Informed Consent Term.The patients included had CRC with surgical indication. Those who lost follow-up shortly after surgery were excluded. For the control group, individuals without colorectal neoplasm and matched by gender and age group were included in relation to the case group. On the other hand, individuals with a history of other neoplasms or with the presence of polyps during colonoscopy were excluded from the sample.From the clinical information of the patients, demographic and anthropometric data were extracted: gender, age, BMI, history of smoking and alcoholism. Blood analysis provided information on lymphocytometry, hemoglobin, calcium, transferrin, albumin, initial and post-operative carcinoembryonic antigen, from lymphocyte copy (absolute) of the leukogram both at admission and at discharge. In addition, it was evaluated the results of the anatomopathological study and staging of the tumor provided by the pathological report and/or the oncologist. Pre-operative rectosigmoidoscopies/colonoscopies were analyzed, containing the description of the size of the preoperative lesion and the site of the tumor. Also, it was taken into consideration the treatments and operations made, the description of the procedure if it was performed and if it was necessary second or third intervention. In order to obtain information about death and survival, telephone contact with patient or family was used to identify the patient’s current situation.Was performed in peripheral vein in vacuum tubes containing anticoagulant (EDTA). The tubes were centrifuged and the nucleated cells (leukocytes) were separated for further DNA extraction or stored in freezer storage at -80° C until the time of extraction. The patterns were transferred to sterile flasks and DNA was obtained after enzymatic digestion in buffer containing proteinase K and SDS and subsequent extraction with organic solvents (phenol/chloroform).After DNA extraction from the samples, the analysis of the polymorphism -765G / C region of the COX-2 gene was evaluated by the technique of PCR of restriction fragment length polymorphism (PCR-RFLP), being the primer for PCR selected according to the genome database . Amplification conditions are determined by these conditions of temperatures and times: 94° C - 3 min; 94° C, 59° C and 72° C for 60 s each, with 35 cycles and 72° C for 5 min. For the proline allele detection, the parameters will be used: 94° C - 3 min; 94° C, 57° C and 72° C for 30 s each, with 35 cycles and 72° C for 5 min. After PCR the products were subjected to cleavage with the restriction enzyme called BstUI (Bsh 1236I) for 8 h at 37° C. The amplified products were subjected to separation by electrophoresis and 2% agarose gel and were stained by Sybr Safe. Amplified fragments of 134 and 23 base pairs (bp) will indicate homozygous for the wild-type allele (-765GG). A single fragment of 157 base pair will indicate homozygosis for the C allele (-765CC) and the presence of three fragment of 157, 134 and 23 base pair will indicate heterozygosis (-765GC).This study had 85 participants. Were selected 25 of them with CRC (age 56.3±12.2 years) and 60 participants of the control group (age 60.5±6.8 years ). Regarding gender, there was a slightly increase on the prevalence of men in the case group , although this difference was not statistically significant.There was a high prevalence of GC and CC genotype in individuals with CRC, noting the association between the presence of COX2 gene polymorphism and susceptibility to CRC in this sample  with the control group, the GC and CC genotypes prevailed in the individuals carrying the CRC. This association was also preserved by subdividing the neoplasm group according to the site of the occurrence of the primary tumor in the right colon and left colon; however, was more strongly significant in lesions from the left colon. These results are consistent with data from some of previous studies, including the meta-analysis of Cao et al and Peng et al, which analyzed 6774 cases of CRC and 9772 controls,,,There is hypothesized that the COX-2 enzyme is involved in the stimulation of cell proliferation and angiogenesis, in the inhibition of apoptosis and in immunological suppression, all events with carcinogenic potential ,,There are many evidence of the influence of the polymorphism -765 G / C region on the genesis of several tumors, such as prostate, breast, ovary, lung, liver cancer and CRCIn Brazil, COX-2 polymorphism studies and the occurrence of colorectal tumors are scarce, and this study is one of the first reports comparing not only the susceptibility to cancer but also the association with tumor topography. In this context, this study contributes to the characterization of the association of the polymorphism in the COX2 gene with the CRC in the Brazilian population, notably more significant in the retossigmoid lesions. Polymorphism research can provide significant future advances, as it will enable the identification of the individuals most susceptible to the risk of tumors, allowing individualization in the therapeutics. Regarding colorectal neoplasm, polymorphic patients with the C allele were potential candidates to the treatment with anti-inflammatory drugs, especially in cases of left colon cancer.Polymorphism in the COX-2 gene is associated with increased susceptibility to colorectal cancer, especially in tumors of the rectosigmoid segment.