Non-coding genome in small cell lung cancer between theoretical view and clinical applications.

Small cell lung cancer (SCLC) is a highly aggressive cancer of the neuroendocrine system, characterized by poor differentiation, rapid growth, and poor overall survival (OS) of patients. Despite the recent advances in the treatment of SCLC recently, the 2-year survival rate of patients with the cancer is only 14-15%, occasioned by the acquired resistance to drugs and serious off-target effects. In humans, the coding region is only 2% of the total genome, and 20% of that is associated with human diseases. Beyond the coding genome are RNAs, promoters, enhancers, and other intricate elements. The non-coding regulatory regions, mainly the non-coding RNAs (ncRNAs), regulate numerous biological activities including cell proliferation, metastasis, and drug resistance. As such, they are potential diagnostic or prognostic biomarkers, and also potential therapeutic targets for SCLC. Therefore, understanding how non-coding elements regulate SCLC development and progression holds significant clinical implications. Herein, we summarized the recent discoveries on the relationship between the non-coding elements including long non-coding RNAs (lncRNA), microRNAs (miRNAs), circular RNA (circRNA), enhancers as well as promotors, and the pathogenesis of SCLC and their potential clinical applications.

Nanoparticle-assisted axillary staging: an alternative approach after neoadjuvant chemotherapy in patients with pretreatment node-positive breast cancers.

PURPOSE: In order to achieve an optimized method of axillary staging after neoadjuvant chemotherapy (NAC) in breast cancer patients with pretreatment positive axillary lymph nodes, we evaluated the feasibility and accuracy of nanoparticle-assisted axillary staging (NAAS) which combines carbon nanoparticles with standard sentinel lymph node biopsy (SLNB) with radioisotope and blue dye. METHODS: Invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0 and received surgeries from November 2020 to March 2021 were included. All patients underwent ipsilateral NAAS followed by axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of axillary staging were calculated. RESULTS: Eighty of 136 (58.8%) breast cancer patients converted to ycN0 after NAC and received NAAS. The DR, NPV and accuracy was 95.0%, 93.3% and 97.4% for NAAS, respectively. And the FNR was 4.2% (2/48) for NAAS, which was lower than that of standard dual-tracer SLNB (SD-SLNB) (9.5%, 4/42). Pretreatment clinical T4 classification was a risk factor for detection failure in NAAS (p = 0.016). When patients with pretreatment inflammatory breast cancers were excluded from analysis, FNR dropped to 2.2% (1/45) for NAAS. CONCLUSION: NAAS revealed great performance in invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0. The application of NAAS reached a better balance between more accurate axillary evaluation and less intervention. Trial registration Chictr.org.cn (ChiCTR2000039814). Registered Nov 11, 2020.

Mechanisms of Resistance to Checkpoint Blockade Therapy.

Immune checkpoint blockades (ICBs), as a major breakthrough in cancer immunotherapy, target CTLA-4 and the PD-1/PD-L1 axis and reinvigorate anti-tumor activities by disrupting co-inhibitory T-cell signaling. With unprecedented performance in clinical trials, ICBs have been approved by FDA for the treatment of malignancies such as melanoma, non-small-cell lung cancer, colorectal cancer, and hepatocellular carcinoma. However, while ICBs are revolutionizing therapeutic algorithms for cancers, the frequently observed innate, adaptive or acquired drug resistance remains an inevitable obstacle to a durable antitumor activity, thus leading to non-response or tumor relapse. Researches have shown that resistance could occur at each stage of the tumor's immune responses. From the current understanding, the molecular mechanisms for the resistance of ICB can be categorized into the following aspects: 1. Tumor-derived mechanism, 2. T cell-based mechanism, and 3. Tumor microenvironment-determined resistance. In order to overcome resistance, potential therapeutic strategies include enhancing antigen procession and presentation, reinforcing the activity and infiltration of T cells, and destroying immunosuppression microenvironment. In future, determining the driving factors behind ICB resistance by tools of precision medicine may maximize clinical benefits from ICBs. Moreover, efforts in individualized dosing, intermittent administration and/or combinatory regimens have opened new directions for overcoming ICB resistance.

Impact of Thrombotic Microangiopathy on Renal Outcomes and Survival after Hematopoietic Stem Cell Transplantation.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a serious complication of hematopoietic stem cell transplantation (HSCT). We characterized the incidence, risk factors, and long-term outcomes associated with TA-TMA by performing a comprehensive review of all adult patients (n = 1990) undergoing allogeneic HSCT at the Dana Farber Cancer Institute/Brigham and Women's Hospital between 2005 and 2013. Using the City of Hope criteria, we identified 258 patients (13%) with "definite" TMA and 508 patients (26%) with "probable" TMA. Mismatched donor transplantation (subdistribution hazard ratio [sHR], 1.79; 95% confidence interval [CI], 1.17 to 2.75; P = .007), sirolimus-containing graft-versus-host disease prophylaxis (sHR, 1.73; 95% CI, 1.29 to 2.34; P < .001), myeloablative conditioning (sHR, 1.93, 95% CI, 1.38 to 2.68; P < .001), and high baseline lactate dehydrogenase (LDH) level (sHR, 1.64; 95% CI, 1.26 to 2.13; P < .001) were associated with definite TMA. Moreover, positive cytomegalovirus serostatus (sHR, 1.41; 95% CI, 1.16 to 1.71; P < .001), high and very high disease risk index (sHR, 1.48; 95% CI, 1.12 to 1.96, P = .007), and high baseline LDH level (sHR, 1.25; 95% CI, 1.05 to 1.49; P = .011) were associated with probable TMA. In multivariable analyses, definite and probable TMA were each independently associated with higher mortality (HR, 5.24; 95% CI, 4.43 to 6.20 and HR, 2.12; 95% CI, 1.84 to 2.44, respectively), and long-term kidney dysfunction (HR, 5.43; 95% CI, 4.61 to 6.40 and HR, 2.20; 95% CI, 1.92 to 2.51, respectively). Definite and probable TMA were also independently associated with an increased risk of nonrelapse mortality and shorter progression-free survival. Our findings indicate that TA-TMA is common following HSCT and is independently associated with increased risk of death and kidney dysfunction.

Extended Daily Dialysis Versus Continuous Renal Replacement Therapy for Acute Kidney Injury: A Meta-analysis.

BACKGROUND: Extended daily dialysis (EDD) has been suggested as an effective renal replacement therapy for acute kidney injury. However, results from studies comparing EDD to continuous renal replacement therapy (CRRT) are inconclusive. STUDY DESIGN: A systematic review and meta-analysis was performed by searching in MEDLINE, EMBASE, the Cochrane Library, Google Scholar, and a Chinese database (SinsoMed). SETTING & POPULATION: Patients with acute kidney injury. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials (RCTs) and observational studies were included. EDD was defined as extended hemodialysis or hemodiafiltration for more than 6 but less than 24 hours per session using a conventional hemodialysis machine. INTERVENTION: Renal replacement therapy comparing EDD with CRRT. OUTCOMES: Mortality, kidney recovery, and fluid removal. RESULTS: We included 17 studies from 2000 to 2014: 7 RCTs and 10 observational studies involving 533 and 675 patients, respectively. Meta-analysis of RCTs showed no difference in mortality rates between EDD and CRRT (relative risk, 0.90; 95% CI, 0.74-1.11; P=0.3). However, EDD was associated with lower mortality risk compared with CRRT in observational studies (relative risk, 0.86; 95% CI, 0.74-1.00; P=0.05). There was no evidence of heterogeneity in RCTs (I(2)=0%) or observational studies (I(2)=15%). In both RCTs and observational studies, there were no significant differences in recovery of kidney function, fluid removal, or days in the intensive care unit, and EDD showed similar biochemical efficacy to CRRT during treatment (serum urea, serum creatinine, and serum phosphate). LIMITATIONS: The survival benefit of EDD is dependent on only observational studies and might have been affected by allocation or selection bias. CONCLUSIONS: EDD is associated with similar outcomes to CRRT in RCTs. The finding that EDD is associated with a lower mortality rate relies on data from observational studies, which are potentially subject to allocation or selection bias, making further high-quality RCTs desirable.

The Three-Dimensional Techniques in the Objective Measurement of Breast Aesthetics.

UNLABELLED: Breast symmetry, size, and shape are key components of aesthetic outcomes of augmentation mammoplasty, reduction, and reconstruction. Many have claimed that the 3D scanning technique, which measures breast volumes directly and assesses the asymmetry of the chest and breast on a 3D model, is superior to anthropometric measuring in accuracy, precision, and reproducibility. The documented methods of 3D body surface imaging include laser scanning, stereo photography and so on. To achieve ideal aesthetic results, individualized surgery planning based on a reliable virtual model of the prospective surgery outcome could be of considerable value in decision making and assisting in guidance for the surgery procedure. Additionally, the 3D scanning technique is applicable in postoperative monitoring of morphological change, notably, in a dynamic way. Another distinguishing feature is that it enables virtual division of breast volume, thus surgeons could virtually divide the breast volumes into portions using 3D scanning during the programming and evaluation of surgery plans. However, because 3D surface scanning cannot look through the breast substances and reach the interspace between the chest and posterior border of the breast/dorsal limit of the breast, the inframammary fold in larger breasts cannot be correctly imaged, leaving the preoperative inframammary fold reference lacking. Therefore, 3D scanning is thought to be inaccurate in large and/or ptotic breasts. Another fact that prevents 3D scanning from wide application is its high cost and lack of access. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Citrate versus heparin lock for hemodialysis catheters: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Citrate solution has been suggested as an effective and safe catheter lock in hemodialysis. However, whether a citrate lock is superior to a heparin lock in preventing catheter-related infections and maintaining catheter patency is inconclusive. STUDY DESIGN: A systematic review and meta-analysis was performed by searching in PubMed, EMBASE, Ovid, the Cochrane Library, and Web of Science databases and major nephrology journals. SETTING & POPULATION: Patients receiving hemodialysis with central venous catheters. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials comparing citrate locks with heparin locks in hemodialysis patients with central venous catheters. INTERVENTION: Locking central venous catheters with citrate locks. OUTCOMES: Primary outcomes include catheter-related bloodstream infection (CRBSI), exit-site infection, catheter removal for poor flow, and thrombolytic treatment. RESULTS: 13 randomized controlled trials (1,770 patients, 221,064 catheter-days) met the inclusion criteria. Pooled analyses found that citrate locks could significantly reduce the incidence of CRBSI (risk ratio [RR], 0.39; 95% CI, 0.27-0.56; P < 0.001). Subgroup analysis showed that antimicrobial-containing citrate locks (citrate + gentamicin, citrate + taurolidine, and citrate + methylene blue + methylparaben + propylparaben) were superior to heparin locks in the prevention of CRBSI (P < 0.001, P = 0.003, and P = 0.008, respectively), whereas citrate alone failed to show a similar advantage (P = 0.2). Low- (1.04%-4%) to moderate-concentration (4.6%-7%) citrate locks were associated with decreased CRBSI incidence (P < 0.001 and P = 0.003, respectively), but patients receiving high-concentration (30%-46.7%) citrate and heparin locks had similar incidences (P = 0.3). The incidence of bleeding episodes (RR, 0.48; 95% CI, 0.30-0.76; P = 0.002) was significantly lower in patients receiving citrate locks, whereas both groups were similar in terms of exit-site infection (P = 0.2), catheter removal for poor flow (P = 0.9), thrombolytic treatment (P = 0.8), all-cause death (P = 0.3), catheter thrombosis (P = 0.9), mean catheter duration (P = 0.2), CRBSI-free catheter survival (P = 0.2), and catheter-related readmission (P = 0.5). LIMITATIONS: All studies used in the meta-analysis were performed in Western countries. The applicability of our findings to other regions remains to be clarified. CONCLUSIONS: An antimicrobial-containing citrate lock is better than a heparin lock in the prevention of catheter-related infection, while citrate alone fails to show a similar advantage. Citrate locks of low to moderate concentrations, rather than high concentration, were superior to heparin locks in preventing CRBSI. Citrate locks also might decrease bleeding episodes. No difference has been identified in the efficacy to prevent exit-site infection or preserve catheter patency between citrate and heparin locks.

The association between the Arg280His polymorphism in the XRCC1 gene and the risk of hematological malignancies.

The associations between the Arg280His polymorphism in X-ray repair cross-complementing gene 1 (XRCC1 gene) and hematological malignancies have been extensively investigated. However, the results were inconsistent. The objective of the current study was to investigate the associations between the Arg280His polymorphism in XRCC1 gene and the risk of hematological malignancies by meta-analysis. We searched PubMed, Embase, CNKI, Wanfang, and Weipu databases, covering all studies until 07 Aug 2013. Statistical analysis was performed by using the Revman4.2 software and the Stata10.0 software. A total of 2,650 cases and 3,856 controls in 12 case-control studies concerning the Arg280His polymorphism were included. The results suggested that the Arg280His polymorphism might not be associated with risk of hematological malignancies (OR = 1.08, 95%CI = 0.86-1.35, P = 0.50). In the subgroup analyses by cancer types and ethnicity, no significant associations were found among different cancers or different ethnicities. The current meta-analysis indicated that the Arg280His polymorphism in the XRCC1 gene might not be a risk factor for hematological malignancies. In future, more large-scale case-control studies are needed to validate these results.

Study on the association between the Arg194Trp polymorphism in the XRCC1 gene and the risk of hematological malignancies.

The association between the Arg194Trp polymorphism in the XRCC1 gene and the risk of hematological malignancies has been extensively investigated. However, the results were inconsistent. The objective of the current study is to investigate the association by meta-analysis. We searched the PubMed, Embase, CNKI, Wanfang, and Weipu databases, covering all studies until Aug. 7, 2013. Statistical analysis was performed by using the RevMan4.2 software and the Stata10.0 software. A total of 20 case-control studies concerning the Arg194Trp polymorphism were indentified from 19 articles. In total analysis, our results suggested that the Arg194Trp polymorphism was not associated with an increased/decreased risk of hematological malignancies (odds ratio (OR) = 1.01, 95 % confidence interval (CI) = 0.85-1.22, P = 0.87 for Arg/Trp+Trp/Trp vs. Arg/Arg). In the subgroup analysis by ethnicity, no significant association was found either among Asians (OR = 1.04, 95% CI = 0.84-1.29, P = 0.72) or among Europeans (OR = 1.04, 95% CI = 0.72-1.49, P = 0.83); in the subgroup analyses by cancer types, no significant association was found either among leukemia (OR = 1.10, 95% CI = 0.89-1.35, P = 0.39) or in lymphoma (OR = 0.83, 95% CI = 0.57-1.22, P = 0.35). The current meta-analysis indicated that the Arg194Trp polymorphism in the XRCC1 gene might be not a risk factor for hematological malignancies. In the future, more large-scale case-control studies are needed to validate these results.

The Thr241Met polymorphism in the XRCC3 gene is associated with increased risk of cancer in Chinese mainland populations.

The Thr241Met polymorphism in XRCC3 gene may affect the DNA repair pathways and be associated with the risk of cancer. However, the results of previous studies are inconsistent in Chinese mainland populations. The objective of this study is to investigate the association between the Thr241Met polymorphism in XRCC3 gene and risk of cancer for the Chinese Mainland populations by meta-analysis. We searched PubMed database, Embase database, CNKI database, and Wanfang database, and the last search was updated on July 24, 2013. Statistical analysis was performed using RevMan4.2 and Stata10.0 software. Finally, a total of 23 case-control studies in 23 articles were included. The results suggested a significant association between the Thr241Met polymorphism in XRCC3 gene and cancer risk in Chinese mainland populations (Met/Met + Thr/Met vs. Thr/Thr: OR = 1.25, 95 % CI = 1.02-1.54, P = 0.04). In the subgroup analyses by cancer types, significant associations were found in cervical cancer and nasopharyngeal cancer. The current meta-analysis suggested that the Thr241Met polymorphism in the XRCC3 gene may be a risk factor for cancer in Chinese mainland populations. In the future, more case-control studies are needed to validate these results.

The -786T > C polymorphism in the NOS3 gene is associated with increased cancer risk.

The -786T > C polymorphism in NOS3 gene may affect the DNA repair pathways and be associated with risk of cancer. However, the results of previous studies are inconsistent. The objective of this study is to investigate the association between the -786T > C polymorphism in NOS3 and risk of cancer by meta-analysis. We searched PubMed, Embase, CNKI, and Wanfang databases and the last search was updated on Sept. 20, 2013. Statistical analysis was performed using Revman4.2 and Stata10.0 software. A total of 9 case-control studies concerning 4,089 cases and 3,847 controls were included. The results suggested a significant association between the -786T > C polymorphism in NOS3 and cancer risk (CC vs. TT + CT; OR = 1.30, 95% CI = 1.07-1.57, P = 0.007) in total analysis. In the subgroup analysis by ethnicity and cancer types, significant associations were found in the breast cancer subgroup (OR 1.51, 95% CI 1.07-2.12; P = 0.02) and European subgroup (OR 1.26, 95% CI 1.01-1.58; P = 0.04). The current meta-analysis suggested that the -786T > C polymorphisms in NOS3 may be a risk factor for cancer. In the future, more case-control studies are needed to validate our results.

The Glu298Asp polymorphism in the NOS3 gene and the risk of prostate cancer.

The Glu298Asp polymorphism in the NOS3 gene has been implicated as a risk factor for prostate cancer. To date, several studies have evaluated the associations between the Glu298Asp polymorphism and prostate cancer risk; however, the results were inconclusive. The aim of the current study was to perform a meta-analysis to investigate the association between the polymorphism and the risk of prostate cancer. A total of 3,206 cases and 3,880 controls from eight case-control studies were included for data synthesis. The overall results suggested no significant association between the polymorphism and the risk of prostate cancer (OR=1.01, 95% CI=0.92-1.11, p = 0.83 for Asp/Asp+Glu/Asp vs. Glu/Glu). In the stratified analysis according to ethnicity, no significant associations were observed in Asians and Europeans. The current meta-analysis suggested that the Glu298Asp polymorphism of the NOS3 gene might not contribute to the risk of prostate cancer.

The association between the Lys751Gln polymorphism in the XPD gene and the risk of bladder cancer.

The Lys751Gln polymorphism in the XPD gene have been suggested as a risk factor for bladder cancer, however the results were inconclusive. The aim of the current study is to assess the association by meta-analysis. A total of 15 case-control studies concerning the association between the XPD Lys751Gln polymorphism and bladder cancer risk were included in the meta-analysis. The results suggested that the Lys751Gln polymorphism was not associated with an increased risk of bladder cancer in the dominant model (OR = 1.03, 95 % CI 0.95-1.11, P = 0.53 for Lys/Gln+Gln/Gln vs. Lys/Lys) in overall analysis. In the subgroup analysis by ethnicity, no significant association was found in Caucasians or Asians. Other comparatives suggested a slight significant association between the polymorphism with the risk of bladder cancer in the recessive comparative (OR = 1.14, 95 % CI 1.02-1.29, P = 0.03). The current meta-analysis indicated that the Lys751Gln polymorphism in the XPD gene might be a risk factor for bladder cancer. In the future, more large-scale case-control studies are needed to validate our results.

Immune pathogenesis of idiopathic granulomatous mastitis: from etiology toward therapeutic approaches.

Idiopathic granulomatous mastitis (IGM) is a noncancerous, chronic inflammatory disorder of breast with unknown causes, posing significant challenges to the quality of life due to its high refractoriness and local aggressiveness. The typical symptoms of this disease involve skin redness, a firm and tender breast mass and mastalgia; others may include swelling, fistula, abscess (often without fever), nipple retraction, and peau d'orange appearance. IGM often mimics breast abscesses or malignancies, particularly inflammatory breast cancer, and is characterized by absent standardized treatment options, inconsistent patient response and unknown mechanism. Definite diagnosis of this disease relies on core needle biopsy and histopathological examination. The prevailing etiological theory suggests that IGM is an autoimmune disease, as some patients respond well to steroid treatment. Additionally, the presence of concurrent erythema nodosum or other autoimmune conditions supports the autoimmune nature of the disease. Based on current knowledge, this review aims to elucidate the autoimmune-favored features of IGM and explore its potential etiologies. Furthermore, we discuss the immune-mediated pathogenesis of IGM using existing research and propose immunotherapeutic strategies for managing this condition.

The associations between the polymorphisms in the CTLA-4 gene and the risk of Graves' disease in the Chinese population.

BACKGROUND: The associations between the polymorphisms in Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) gene and Graves' disease (GD) have been extensively investigated in Chinese population. However, the results were inconsistent. The objective of this study is to investigate the associations between the polymorphisms in CTLA-4 gene and the risk of GD by meta-analysis. METHODS: We searched Pubmed database, Medline (Ovid) database, CNKI database and Wanfang database, covering all studies until August 11, 2012. Statistical analysis was performed by using the Revman4.2 software and the Stata10.0 software. RESULTS: A total of 28 case-control studies concerning the most widely studied three polymorphisms [+49A/G(rs231775), -318C/T(rs5742909) and CT60(rs3087243)] for Chinese population in 21 publications were included. The results suggested that the G allele carriers (GG+GA) might have an increased risk of GD when compared with the AA homozygote carriers for the +49A/G polymorphism (GG+GA vs. AA: OR = 2.57, 95%CI = 1.87-3.52). However, as to the -318C/T polymorphism and CT60 polymorphism, the results indicated that the variant allele carriers might have decreased risks of GD when compared with the homozygote carriers (-318C/T: TT+TC vs. CC: OR = 0.78, 95%CI = 0.62-0.97; CT60: AA+AG vs. GG: OR = 0.64, 95%CI = 0.52-0.78). CONCLUSIONS: The current meta-analysis indicated that the polymorphisms in the CLTA-4 gene might be risk factors for GD in the Chinese population. In future, more large-scale case-control studies are needed to validate these results.

The association between the poly(A) polymorphism in the VDR gene and cancer risk: a meta-analysis.

The poly(A) polymorphism (L/S) in the VDR gene has been implicated in susceptibility of cancer, but a number of studies have reported inconclusive results. The aim of this study is to investigate the relationship between the poly(A) polymorphism in the VDR gene and cancer risk by meta-analysis. We searched PubMed database, EMBASE database, CNKI database, and Wanfang database, covering all studies until January 22, 2013. Statistical analysis was performed by using the software Revman4.2 and STATA 10.0. A total 8,186 cancer cases and 8,685 controls in 19 case-control studies from 15 studies were identified for data analysis. The results suggested that the S allele carriers (SS+SL) did not have an increased or decreased risk of cancer when compared with the homozygote LL carriers (odds ratio (OR) =0.96, 95 % CI=0.87-1.06, P=0.43 for SS+SL vs. LL). In addition, in the subgroup analysis by ethnicity and cancer type, no significant association was found among Caucasians, African-Americans, prostate cancer, or breast cancer. This current meta-analysis suggested that the poly(A) polymorphism in the VDR gene may not contribute to the risk of cancer. Future studies are needed to validate our findings.

The polymorphisms in the MGMT gene and the risk of cancer: a meta-analysis.

Polymorphisms in the MGMT gene have been implicated in susceptibility to cancer, but the published studies have reported inconclusive results. The objective of the current study was to investigate the genetic risk of polymorphisms in the MGMT gene for cancer. A meta-analysis was carried out to analyze the association between polymorphisms in the MGMT gene and cancer risk. Five polymorphisms (Leu84Phe, Leu53Leu, Ile143Val, Lys178Arg, and -485C/A) with 98 case-control studies from 49 articles were analyzed. The results indicated that individuals who carried the Phe/Phe homozygote genotype of Leu84Phe had a 31 % increased risk of cancer compared with the Leu allele (Leu + Leu/Phe) carriers (odds ratio [OR] = 1.32, 95 % confidence interval [CI] = 1.15-1.52, P < 0.0001 for Phe/Phe vs. Phe/Leu + Leu/Leu). However, there was no significant association between the risk of cancer and the other four polymorphisms (Leu53Leu, Ile143Val, Lys178Arg, and -485C/A). In further stratified analyses for the Leu84Phe and Ile143Val polymorphisms, the increased risk of cancer remained in subgroups of Caucasians, patients with esophageal cancer for the Leu84Phe polymorphism, and patients with lung cancer for the Ile143Val polymorphism. Results from the current meta-analysis suggested that Leu84Phe and Ile143Val in the MGMT gene are risk factors for cancer. In the future, more studies should be performed to validate our results.