Cyclin D1 G870A polymorphism and colorectal cancer susceptibility: a meta-analysis of 20 populations.

PURPOSE: Studies investigating the association between genetic polymorphism of cyclin D1 (CCND1) G870A and risk of colorectal cancer (CRC) reported conflicting results. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. MATERIALS AND METHODS: We performed an extensive search of relevant studies and carried out a meta-analysis, including 20 studies with 5,975 cases and 8,333 controls, to obtain a more precise estimate. RESULTS: Overall, significantly elevated colorectal cancer risk was associated with variant allele 870A when all studies were pooled (AA vs. GG: OR = 1.23, 95% CI = 1.04-1.44; GA vs. GG: OR = 1.13, 95% CI = 1.01-1.26; dominant model: OR = 1.16, 95% CI = 1.03-1.31). In the subgroup analysis by ethnicity, significantly increased risks were detected among Caucasians (AA vs. GG: OR = 1.27, 95% CI = 1.04-1.44; dominant model: OR = 1.17, 95% CI = 1.02-1.34).We also observed sporadic CRC with an increased cancer susceptibility (AA vs. GG: OR = 1.24, 95% CI = 1.04-1.48; dominant model: OR = 1.17, 95% CI = 1.04-1.33), when colorectal cancer was stratified into sporadic CRC and hereditary nonpolyposis colorectal cancer (HNPCC). However, no significant associations were found in both Asians and HNPCC patients for all genetic models. CONCLUSION: Result suggests that the cyclin D1 870A allele is a low-penetrant risk factor for developing sporadic colorectal cancer, especially among Caucasians.

MicroRNA-143 inhibits tumor growth and angiogenesis and sensitizes chemosensitivity to oxaliplatin in colorectal cancers.

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Recently, downregulation of microRNA-143 (miR-143) has been observed in CRC tissues. Here in this study, we found that miR-143 expression was downregulated both in CRC patients' blood samples and tumor specimens. MiR-143 expression levels were strongly correlated with clinical stages and lymph node metastasis. Furthermore, insulin-like growth factor-I receptor (IGF-IR), a known oncogene, was a novel direct target of miR-143, whose expression levels were inversely correlated with miR-143 expression in human CRC specimens. Overexpression of miR-143 inhibited cell proliferation, migration, tumor growth and angiogenesis and increased chemosensitivity to oxaliplatin treatment in an IGF-IR-dependent manner. Taken together, these results revealed that miR-143 levels in human blood and tumor tissues are associated with CRC cancer occurrence, metastasis and drug resistance, and miR-143 levels may be used as a new diagnostic marker and therapeutic target for CRC in the future.

Prognostic value of survivin in patients with non-small cell lung carcinoma: a systematic review with meta-analysis.

PURPOSE: The potential prognostic value of survivin in resected non-small cell lung carcinoma (NSCLC) is variably reported. The objective of this study was to conduct a systematic review of literatures evaluating survivin expression in resected NSCLC as a prognostic indicator. METHODS: Relevant literatures were identified using PubMed, EMBASE and Chinese Biomedicine Databases. We present the results of a meta-analysis of the association between survivin expression and overall survival (OS) in NSCLC patients. Studies were pooled and summary hazard ratios (HR) were calculated. Subgroup analyses and publication bias were also conducted. RESULTS: We performed a final analysis of 2703 patients from 28 evaluable studies. Combined HRs suggested that survivin overexpression had an unfavorable impact on NSCLC patients' survival with no evidence of any significant publication bias (HR = 2.03, 95%CI: 1.78-2.33, Egger's test, P = 0.24) and no severe heterogeneity between studies (I²  =  26.9%). Its effect also appeared significant when stratified according to the studies categorized by histological type, HR estimate, patient race, cutoff point (5%, 10%), detection methods and literature written language except for disease stage. Survivin was identified as a prognostic marker of advanced-stage NSCLC (HR = 1.93, 95%CI: 1.49-2.51), but not early-stage NSCLC (HR = 1.97, 95%CI: 0.76-5.14), in spite of the combined data being relatively small. CONCLUSION: This study shows that survivin expression appears to be a pejorative prognostic factor in terms of overall survival in surgically treated NSCLC. Large prospective studies are now needed to confirm the clinical utility of survivin as an independent prognostic marker.

Absence of association between N-acetyltransferase 2 acetylator status and colorectal cancer susceptibility: based on evidence from 40 studies.

BACKGROUND AND OBJECTIVES: N-Acetyltransferase (NAT) 2 is an important enzyme involved in the metabolism of different xenobiotics, including potential carcinogens, whose phenotypes were reported to be related to individual susceptibility to colorectal cancer (CRC). However, the results remain conflicting. To assess the relationship between NAT2 phenotypes and CRC risk, we performed this meta-analysis. METHODS: A comprehensive literature search was conducted to identify all case-control or cohort studies of NAT2 acetylator status on the susceptibility of CRC by searching of PubMed and EMBASE, up to May 20, 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. RESULTS: A total of over 40,000 subjects from 40 published literatures were identified by searching the databases. No significantly elevated CRC risk in individuals with NAT2 slow acetylators compared with fast acetylators was found when all studies pooled (OR = 0.95, 95% CI: 0.87-1.04, I(2) = 52.6%). While three studies contributed to the source of heterogeneity were removed, there was still null result observed (OR = 0.96, 95% CI: 0.90-1.03, P = 0.17 for heterogeneity, I(2) = 17.8%). In addition, we failed to detect any associations in the stratified analyses by race, sex, source of controls, smoking status, genotyping methods or tumor localization. No publication bias was observed in this study. CONCLUSIONS: This meta-analysis suggests that the NAT2 phenotypes may not be associated with colorectal cancer development.

The role of cyclin D1 expression and patient's survival in non-small-cell lung cancer: a systematic review with meta-analysis.

BACKGROUND: The role of cell-cycle protein cyclin D1 in lung cancer remains controversial. To clarify its impact on survival in non-small-cell lung cancer (NSCLC), we performed a meta-analysis on the currently available medial literature to quantitatively assess its role on survival of NSCLC according to cyclin D1 status. METHOD: Published studies that investigated the association between cyclin D1 expression and NSCLC survival were identified. Meta-analysis was performed by using a DerSimonian-Laird model. Funnel plot was used to investigate publication bias and sources of heterogeneity were identified by using meta-regression analysis. RESULT: A total of 24 studies with 2731 patients were evaluable for this meta-analysis. No statistical significance was found that cyclin D1 expression was associated with poor prognosis in NSCLC (hazard ratio 1.08 [95% CI, 0.80-1.45]) without publication bias found. But there was significant heterogeneity present; meta-regression analysis was used to explore the sources of heterogeneity and revealed that the outcome of analysis was influenced by cutoff values and ethnicity. No difference between positive and negative studies on study quality assessment was present. CONCLUSION: The cyclin D1 expression is unlikely to be useful as a prognostic marker for NSCLC in clinical practice from current evidence. The conclusion should be confirmed by a large well-designed prospective study.

The cyclin D1 G870A polymorphism and colorectal cancer susceptibility: a meta-analysis of 20 populations.

PURPOSE: Studies of the association between the cyclin D1 (CCND1) G870A genetic polymorphism and risk of colorectal cancer (CRC) have generated conflicting results. In order to derive a more precise estimation, a meta-analysis was here performed. MATERIALS AND METHODS: An extensive search of relevant studies was carried out as a meta-analysis of twenty studies with 5,975 cases and 8,333 controls. RESULTS: Overall, a significantly elevated colorectal cancer risk was associated with variant allele 870A when all studies were pooled (AA vs. GG: OR = 1.23, 95%CI = 1.04-1.44; GA vs. GG: OR = 1.13, 95% CI = 1.01-1.26; dominant model: OR = 1.16, 95%CI = 1.03-1.31). In the subgroup analysis by ethnicity, significantly increased risks were detected among Caucasians (AA vs. GG: OR = 1.27, 95%CI = 1.04-1.44; and dominant model: OR = 1.17, 95%CI = 1.02-1.34). With stratification into sporadic CRC and hereditary nonpolyposis colorectal cancer (HNPCC), the former demonstrated increased cancer susceptibility (AA vs. GG: OR = 1.24, 95%CI = 1.04-1.48; dominant model: OR = 1.17, 95%CI = 1.04-1.33). However, no significant associations were found in either Asians or HNPCC patients for any genetic model. CONCLUSION: The results suggest that the cyclin D1 870A allele is a low-penetrant risk factor for development of sporadic colorectal cancer, especially among Caucasians.