Woong Ju

Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials

Objective To assess the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases. Design Meta-analysis of randomised controlled trials. Data sources and study selection PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov searched in June and November 2012. Two authors independently reviewed and selected eligible randomised controlled trials, based on predetermined selection criteria. Results Out of 2240 articles retrieved from databases and relevant bibliographies, 50 randomised controlled trials with 294 478 participants (156 663 in intervention groups and 137 815 in control groups) were included in the final analyses. In a fixed effect meta-analysis of the 50 trials, supplementation with vitamins and antioxidants was not associated with reductions in the risk of major cardiovascular events (relative risk 1.00, 95% confidence interval 0.98 to 1.02; I2=42%). Overall, there was no beneficial effect of these supplements in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, provider of supplements, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation was associated with a marginally increased risk of angina pectoris, while low dose vitamin B6 supplementation was associated with a slightly decreased risk of major cardiovascular events. Those beneficial or harmful effects disappeared in subgroup meta-analysis of high quality randomised controlled trials within each category. Also, even though supplementation with vitamin B6 was associated with a decreased risk of cardiovascular death in high quality trials, and vitamin E supplementation with a decreased risk of myocardial infarction, those beneficial effects were seen only in randomised controlled trials in which the supplements were supplied by the pharmaceutical industry. Conclusion There is no evidence to support the use of vitamin and antioxidant supplements for prevention of cardiovascular diseases.

Diagnostic performance of computer tomography, magnetic resonance imaging, and positron emission tomography or positron emission tomography/computer tomography for detection of metastatic lymph nodes in patients with cervical cancer : Meta-analysis

We performed a meta‐analysis to compare diagnostic performances of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET or PET/CT), for detection of metastatic lymph nodes in patients with cervical cancer. We searched MEDLINE (PubMed), EMBASE and the Cochrane Review database in December 2007. All articles were independently reviewed and selected by three evaluators. We estimated a summary receiver operating characteristic (sROC) curve. The area under the curve (AUC), Q*, and pooled weighted estimates of sensitivity and specificity for each modality by patient‐based and region‐ or node‐based data analyses and conducted pair‐wise comparisons between modalities using the two‐sample Z‐test. Forty‐one of 768 initially identified studies were included in the meta‐analysis. In a patient‐based data analysis, PET or PET/CT showed the highest pooled sensitivity (82%) and specificity (95%), while CT showed 50% and 92%; and MRI, 56% and 91%, respectively. The AUC (0.9641) and Q* (0.9106) of PET or PET/CT were significantly higher than those of MRI (AUC = 0.8270; Q* = 0.7599), both P < 0.001. In region‐ or node‐based data analysis, sensitivities of CT (52%) and PET or PET/CT (54%) were higher than that of MRI (38%), P < 0.02 and P < 0.001, respectively, while specificities of MRI (97%) and PET or PET/CT (97%) were higher than that of CT (92%), both P < 0.001. The AUC and Q* showed no significant difference among CT, MRI, and PET or PET/CT. PET or PET/CT had an overall higher diagnostic performance than did CT or MRI in detecting metastatic lymph nodes in patients with cervical cancer. (Cancer Sci 2010)

Adult Weight Gain and Adiposity-Related Cancers: A Dose-Response Meta-Analysis of Prospective Observational Studies

BACKGROUND Adiposity, measured by body mass index, is implicated in carcinogenesis. While adult weight gain has diverse advantages over body mass index in measuring adiposity, systematic reviews on adult weight gain in relation to adiposity-related cancers are lacking. METHODS PubMed and Embase were searched through September 2014 for prospective observational studies investigating the relationship between adult weight gain and the risk of 10 adiposity-related cancers. Dose-response meta-analyses were performed using a random-effects model to estimate summary relative risk (RR) and 95% confidence interval (CI) for each cancer type. All statistical tests were two-sided. RESULTS A total of 50 studies were included. For each 5 kg increase in adult weight gain, the summary relative risk was 1.11 (95% CI = 1.08 to 1.13) for postmenopausal breast cancer among no- or low-hormone replacement therapy (HRT) users, 1.39 (95% CI = 1.29 to 1.49) and 1.09 (95% CI = 1.02 to 1.16) for postmenopausal endometrial cancer among HRT nonusers and users, respectively, 1.13 (95% CI = 1.03 to 1.23) for postmenopausal ovarian cancer among no or low HRT users, 1.09 (95% CI = 1.04 to 1.13) for colon cancer in men. The relative risk of kidney cancer comparing highest and lowest level of adult weight gain was 1.42 (95% CI = 1.11 to 1.81). Adult weight gain was unrelated to cancers of the breast (premenopausal women, postmenopausal HRT users), prostate, colon (women), pancreas, and thyroid. An increase in risk associated with adult weight gain for breast cancer was statistically significantly greater among postmenopausal women (P(heterogeneity) = .001) and HRT nonusers (P(heterogeneity) = .001); that for endometrial cancer was alike among HRT nonusers (P(heterogeneity) = .04). CONCLUSIONS Avoiding adult weight gain itself may confer protection against certain types of cancers, particularly among HRT nonusers.

Mobile Phone Use and Risk of Tumors: A Meta-Analysis

PURPOSE Case-control studies have reported inconsistent findings regarding the association between mobile phone use and tumor risk. We investigated these associations using a meta-analysis. METHODS We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in August 2008. Two evaluators independently reviewed and selected articles based on predetermined selection criteria. RESULTS Of 465 articles meeting our initial criteria, 23 case-control studies, which involved 37,916 participants (12,344 patient cases and 25,572 controls), were included in the final analyses. Compared with never or rarely having used a mobile phone, the odds ratio for overall use was 0.98 for malignant and benign tumors (95% CI, 0.89 to 1.07) in a random-effects meta-analysis of all 23 studies. However, a significant positive association (harmful effect) was observed in a random-effects meta-analysis of eight studies using blinding, whereas a significant negative association (protective effect) was observed in a fixed-effects meta-analysis of 15 studies not using blinding. Mobile phone use of 10 years or longer was associated with a risk of tumors in 13 studies reporting this association (odds ratio = 1.18; 95% CI, 1.04 to 1.34). Further, these findings were also observed in the subgroup analyses by methodologic quality of study. Blinding and methodologic quality of study were strongly associated with the research group. CONCLUSION The current study found that there is possible evidence linking mobile phone use to an increased risk of tumors from a meta-analysis of low-biased case-control studies. Prospective cohort studies providing a higher level of evidence are needed.

Effects of antioxidant supplements on cancer prevention: meta-analysis of randomized controlled trials

BACKGROUND This meta-analysis aimed to investigate the effect of antioxidant supplements on the primary and secondary prevention of cancer as reported by randomized controlled trials. METHODS We searched Medline (PubMed), Excerpta Medica database, and the Cochrane Review in October 2007. RESULTS Among 3327 articles searched, 31 articles on 22 randomized controlled trials, which included 161 045 total subjects, 88 610 in antioxidant supplement groups and 72 435 in placebo or no-intervention groups, were included in the final analyses. In a fixed-effects meta-analysis of all 22 trials, antioxidant supplements were found to have no preventive effect on cancer [relative risk (RR) 0.99; 95% confidence interval (CI) 0.96-1.03). Similar findings were observed in 12 studies on primary prevention trials (RR 1.00; 95% CI 0.97-1.04) and in nine studies on secondary prevention trials (RR 0.97; 95% CI 0.83-1.13). Further, subgroup analyses revealed no preventive effect on cancer according to type of antioxidant, type of cancer, or the methodological quality of the studies. On the other hand, the use of antioxidant supplements significantly increased the risk of bladder cancer (RR 1.52; 95% CI 1.06-2.17) in a subgroup meta-analysis of four trials. CONCLUSIONS The meta-analysis of randomized controlled trials indicated that there is no clinical evidence to support an overall primary and secondary preventive effect of antioxidant supplements on cancer. The effects of antioxidant supplements on human health, particularly in relation to cancer, should not be overemphasized because the use of those might be harmful for some cancer.

Association between excision repair cross-complementation group 1 polymorphism and clinical outcome of platinum-based chemotherapy in patients with epithelial ovarian cancer

ERCC1 is a DNA repair gene and has been associated with resistance to DNA damaging agents. In this study we hypothesized that a polymorphism of ERCC1 Asn118Asn (C→T) might affect the platinum-resistance of epithelial ovarian cancer patients to platinum-taxane chemotherapy administered postoperatively. Using the SNapShot assay, we assessed this polymorphism in ERCC1 in 60 ovarian cancer patients. Platinum-resistance was defined as progression on platinum-based chemotherapy or recurrence within 6 months of completing therapy. Although not significant, platinum-resistance was less frequently observed in patients with the C/T+T/T genotype (P=0.064). Multivariate analysis showed that the C/T+T/T genotypes constituted an independent predictive factor of reduced risk of platinum-resistance in ovarian cancer (odds ratio 0.17, 95% confidence interval 0.04-0.74, P=0.018, Fishers exact test). No significant correlation was observed between overall survival and the ERCC1 polymorphism. Our results suggest that genotyping of the ERCC1 polymorphism Asn118Asn may be useful for predicting the platinum-resistance of epithelial ovarian cancer patients. However, these findings require prospective confirmation.

Calcium intake and colorectal cancer risk: Dose-response meta-analysis of prospective observational studies.

Mechanistic and epidemiologic studies provide considerable evidence for a protective association between calcium intake and incident colorectal cancer (CRC). While the relationship has not been substantiated by short‐duration randomized controlled trials (RCTs) of CRC, trials do show a benefit on adenomas, a precursor to CRC. To address some of this inconsistency, we conducted dose–response meta‐analyses by sources of calcium intake, based on prospective observational studies published up to December 2013 identified from PubMed, Embase, and BIOSIS. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random‐effects model. For total calcium intake, each 300 mg/day increase was associated with an approximately 8% reduced risk of CRC (summary RR = 0.92, 95% CI = 0.89–0.95, I2 = 47%, 15 studies with 12,305 cases, intake = 250–1,900 mg/day, follow‐up = 3.3–16 years). While the risk decreased less steeply in higher range of total calcium intake (Pnon‐linearity = 0.04), the degree of curvature was mild and statistical significance of non‐linearity was sensitive to one study. For supplementary calcium, each 300 mg/day increase was associated with an approximately 9% reduced risk of CRC (summary RR = 0.91, 95% CI = 0.86–0.98, I2 = 67%, six studies with 8,839 cases, intake = 0–1,150 mg/day, follow‐up = 5–10 years). The test for non‐linearity was not statistically significant (Pnon‐linearity = 0.11). In conclusion, both dietary and supplementary calcium intake may continue to decrease CRC risk beyond 1,000 mg/day. Calcium supplements and non‐dairy products fortified with calcium may serve as additional targets in the prevention of CRC. RCTs of calcium supplements with at least 10 years of follow‐up are warranted to confirm a benefit of calcium supplements on CRC risk.

Green tea consumption and risk of stomach cancer: A meta‐analysis of epidemiologic studies

This meta‐analysis investigated the quantitative association between the consumption of green tea and the risk of stomach cancer in epidemiologic studies using crude data and adjusted data. We searched MEDLINE, EMBASE and the Cochrane Review in August 2007. All the articles searched were independently reviewed and selected by 3 evaluators according to predetermined criteria. A total of 13 epidemiologic studies were included. When all the case–control and cohort studies were pooled, the relative risks (RR) of stomach cancer for the highest level of green tea consumption when compared with the lowest level of consumption were shown to be 1.10 (95% confidence interval (CI), 0.92–1.32) using the crude data and 0.82 (95% CI, 0.70–0.96) using the adjusted data. In the meta‐analyses of case–control studies, no significant association was seen between green tea consumption and stomach cancer using the crude data (RR, 0.79; 95% CI, 0.58–1.07), but green tea was shown to have a preventive effect on stomach cancer using the adjusted data (RR, 0.73; 95% CI, 0.64–0.83). In the meta‐analyses of the recent cohort studies, the highest green tea consumption was shown to significantly increase stomach cancer risk using the crude data (RR, 1.59; 95% CI, 1.16–2.18), but no significant association between them was seen when using the adjusted data (RR, 1.04; 95% CI, 0.93–1.17). Unlike the case–control studies, no preventive effect on stomach cancer was seen for the highest green tea consumption in the meta‐analysis of the recent cohort studies. Further clinical trials are needed.

Identification of genes with differential expression in chemoresistant epithelial ovarian cancer using high-density oligonucleotide microarrays.

A major obstacle in treatment of epithelial ovarian cancer is chemoresistance. The aim of this study was to determine whether distinct gene expression profiles are associated with chemoresistance in epithelial ovarian carcinoma. We performed global gene expression analysis in 13 primary epithelial ovarian cancer tissues including 5 primary chemosensitive tumors and 8 primary chemoresistant tumors using Affymetrix HGU133A microarray. The gene expression patterns of chemosensitive tumors were compared with those of chemoresistant tumors using fold change. Validity of microarray results was examined by semiquantitative RT-PCR. We identified over 320 genes differentially expressed in chemoresistant epithelial ovarian cancer (> or = twofold). Upregulated genes in chemoresistant tumors included cell cycle regulating genes (TOP2A, BCAT1, CDCA8, CCNA2, CENPE), and genes with previously known mechanisms in tumorigenesis (S100A9, APOA1, RNF125, IFI16). Downregulated genes in chemoresistant tumors included genes related to cell adhesion (MUC5B, CITED2), transcription regulating genes (FOXD1, MAD1L1, PAX2), genes involving signal transduction (SOSTDC1, SNX1, SFRP1, FOXA2, PLK2), and stress protein gene (TP53AP1). These data show that gene expression profiling can discriminate primary chemoresistant from primary chemosensitive ovarian cancers. This type of molecular profiling could provide a basis for additional functional studies.

Soy intake and risk of endocrine-related gynaecological cancer: a meta-analysis.

Background  Epidemiology studies have reported associations between soy intake and the risk of endocrine‐related gynaecological cancers. However, to date there have been no quantitative meta‐analyses reported regarding this topic.