• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4691-4698
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• 2015

Background: The tumor suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. However, available results for the prognostic value of PTEN expression in patients with cancer remain controversial. Therefore, a meta-analysis of published studies investigating this issue was performed. Materials and Methods: A literature search via PubMed and EMBASE databases was conducted. Statistical analysis was performed by using the STATA 12.0 (STATA Corp., College, TX). Data from eligible studies were extracted and included into the meta-analysis using a random effects model. Results: A total of 3,810 patients from 27 studies were included in the meta-analysis, 22 investigating the relationship between PTEN expression and overall survival (OS) using univariate analysis, and nine with multivariate analysis. The pooled hazard ratio (HR) for OS was 1.64 (95% confidence interval (CI): 1.32-2.05) by univariate analysis and 1.56 (95% CI: 1.20-2.03) by multivariate analysis. In addition, eight papers including two disease-free-survival analyses (DFSs), four relapse-free-survival analyses (RFSs), three progression-free-survival analyses (PFSs) and one metastasis-free-survival analysis (MFS) reported the effect of PTEN on survival. The results showed that loss of PTEN expression was significant correlated with poor prognosis, with a combined HR of 1.74 (95% CI: 1.24-2.44). Furthermore, in the stratified analysis by the year of publication, ethnicity, cancer type, method, cut-off value, median follow-up time and neoadjuvant therapy in which the study was conducted, we found that the ethnicity, cancer type, method, median follow-up time and neoadjuvant therapy are associated with prognosis. Conclusions: Our study shows that negative or loss of expression of PTEN is associated with worse prognosis in patients with cancer. However, adequately designed prospective studies need to be performed for confirmation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.441-447
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• 2013

Background: Prior studies examining the relation between diabetes mellitus (DM) and prostate cancer risk have reported controversial findings. We examined this association by conducting a detailed meta-analysis of the peer-reviewed literature. Methods: A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to November, 2012 was performed. Methodological quality assessment of the trials was based on the Newcastle-Ottawa Scaleq and the meta-analysis was performed using STATA 12.0. Dose-response regression was conducted with SPSS 19.0. Results: We included 29 studies in the meta-analysis (13 case-control studies, 16 cohort studies), and found an inverse association between DM and prostate cancer (relative risk (RR) 0.84, 95% confidence interval (CI), 0.78-0.91). An inverse association was also observed in non-Asian populations (RR 0.81, 95% CI 0.76-0.87) and population-based studies (RR 0.80, 95% CI 0.77-0.91). No statistical significance was found of the association between prostate cancer risk and the duration of DM (p=0.338), and risk seemed not related with the age of DM diagnosis. Conclusions: This study suggested an inverse relationship between DM and prostate cancer, but without links to duration of disease or age of diagnosis.

• Journal of Preventive Medicine and Public Health
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• v.49 no.6
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• pp.367-375
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• 2016

Objectives: The established theory that breast density is an independent predictor of breast cancer risk is based on studies targeting white women in the West. More Asian women than Western women have dense breasts, but the incidence of breast cancer is lower among Asian women. This meta-analysis investigated the association between breast density in mammography and breast cancer risk in Asian women. Methods: PubMed and Scopus were searched, and the final date of publication was set as December 31, 2015. The effect size in each article was calculated using the interval-collapse method. Summary effect sizes (sESs) and 95% confidence intervals (CIs) were calculated by conducting a meta-analysis applying a random effect model. To investigate the dose-response relationship, random effect dose-response meta-regression (RE-DRMR) was conducted. Results: Six analytical epidemiology studies in total were selected, including one cohort study and five case-control studies. A total of 17 datasets were constructed by type of breast density index and menopausal status. In analyzing the subgroups of premenopausal vs. postmenopausal women, the percent density (PD) index was confirmed to be associated with a significantly elevated risk for breast cancer (sES, 2.21; 95% CI, 1.52 to 3.21; $I^2=50.0%$). The RE-DRMR results showed that the risk of breast cancer increased 1.73 times for each 25% increase in PD in postmenopausal women (95% CI, 1.20 to 2.47). Conclusions: In Asian women, breast cancer risk increased with breast density measured using the PD index, regardless of menopausal status. We propose the further development of a breast cancer risk prediction model based on the application of PD in Asian women.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.5981-5984
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• 2012

Background: Numerous studies have investigated the association of matrix metalloproteinase 1 (MMP1) rs1799750 single nucleotide polymorphism with lung cancer susceptibility, but the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate any possible association. Methods: We searched publications from MEDLINE, EMBASE and CNKI databases which assessed links between the MMP1 rs1799750 polymorphism and lung cancer risk. We calculated the pooled odds ratio (OR) and its 95% confidence interval (95%CI) using either fixed-effects or random-effects models. Results: The meta-analysis was based on 9 publications encompassing 4,823 cases and 4,298 controls. The overall results suggested there was a significant association between the MMP1 rs1799750 polymorphism and lung cancer risk (1G vs. 2G: OR = 0.83, 95%CI = 0.73-0.94; 1G1G vs. 2G2G: OR = 0.73, 95%CI = 0.59-0.92; 1G1G vs. 1G2G/2G2G: OR = 0.87, 95%CI = 0.79-0.97; 1G1G/1G2G vs. 2G2G: OR = 0.78, 95%CI = 0.64-0.95). In the subgroup analysis by ethnicity, the association was still obvious in Asians (all P values < 0.05), but there was no association in Caucasians (all P values > 0.05). Conclusions: The MMP1 rs1799750 polymorphism is associated with decreased lung cancer risk, and a race-specific effect may exist in this association.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3507-3511
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• 2014

Background: The prostaglandin-endoperoxide synthase 2 [PTGS2, commonly known as cyclooxygenase-2 (COX-2)] is an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue and involved in the synthesis of prostaglandins and thromboxanes, regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether a functional genetic polymorphism, rs5277, in COX-2 may have a risk-modifying effect on sporadic colorectal cancer in an Iranian population. Materials and Methods: We conducted a case-control study on 167 patients with colorectal cancer and 197 cancer-free controls in Taleghani Hospital in Tehran, Iran, between 2007 and 2011. Peripheral blood samples of both groups were processed for DNA extraction and genotyping of the COX-2 gene polymorphism (rs5277) using PCR-RFLP. RFLP results were confirmed by direct sequencing. Logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (95% CI). Results: There was no significant difference in the distribution of COX-2 gene rs5277 polymorphism genotype and the allelic form, among CRC patients compared with the healthy control group (p: 0.867). Conclusions: Our results suggest that rs5277 polymorphism in COX2 could not be a good prognostic indicator for patients with CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2363-2367
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• 2014

The association between the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. Although our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between gastric cancer patients and controls, in the meta analysis involving 4,000 subjects, comparison of alleles 609T and 609C indicated a significantly increased risk (46%) for gastric cancer (95% confidence interval (95%CI) for odds ratio (OR)=1.20-1.79) in individuals with the T allele. The tendency was similar to the homozygote (OR=1.81, 95%CI: 1.16-2.84), dominant models (OR=1.41, 95%CI: 1.12-1.79), as well as recessive model (OR=1.58, 95%CI: 1.06-2.35). Stratified analysis by study design demonstrated stronger associations in population-based than in hospital-based studies. And ethnicity-based analysis demonstrated a significant association in Asians. We conclude that the NQO1 gene C609T polymorphism increases the risk for gastric cancer, especially in Asian populations.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2049-2053
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• 2016

Background: The LigaSure vessel sealing system has been proposed to save operation time and reduce intraoperative blood loss for various surgeries. However, its usage for gastric cancer is still controversial. The aim of the present meta-analysis was to compare the effectiveness of LigaSure with conventional surgery in gastrectomy. Materials and Methods: Sources were retrieved from the Cochrane Library, MEDLINE, EMBASE, SCOPUS and Google Scholar until February, 2015. All randomized controlled trials comparing LigaSure with conventional surgery in curative gastric cancer resection were selected. After data extraction, statistics were performed by Review Manager 5.1 software. Results: Three eligible randomized controlled trials were evaluated, with a total of 335 patients. The quality of the included trials was good, yet some methodological and clinical heterogeneity existed. There were no significant differences between the LigaSure and conventional groups in operative time (weighted mean difference [WMD], -22.95 minutes; 95% confidence interval [CI], [-59.75, 13.85]; P = 0.22), blood loss (WMD, -45.8 ml; 95% CI, [-134.5, 42.90]; P = 0.31), nor the incidence of surgical complications (odds ratio, 1.18; 95% CI, [0.68, 2.05]; P = 0.54). But there was a longer duration of hospital stay in LigaSure group (WMD, 1.41 days; 95% CI, [0.14, 2.68]; P = 0.03). Conclusions: All available randomized evidence has been summarized. LigaSure does not confer significant advantage over conventional surgery for curative gastric cancer resection. The usefulness of the device may be limited in gastrectomy. But, more trials are needed for further assessment of the LigaSure system for gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.1023-1029
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• 2014

Background: The purpose of our study was to elucidate the joint effects of combined smoking and alcohol intake on esophageal cancer mortality in Japanese men through a large cohort study with a 20-year follow-up period. Materials and Methods: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s, including 46,395 men and 64,190 women aged 40 years and older and younger than 80. Follow-up of these participants was conducted until 2009. We used the Cox proportional hazards model to analyze data for 42,408 people excluding female participants, 411 people with histories of malignant neoplasms, and 3,576 with unclear smoking and drinking data. Results: The joint effects of age at start of smoking and amount of alcohol consumed per day were compared with non-smokers and non-drinkers or those consuming less than one unit of alcohol per day. The mortality risk was 9.33 (95% confidence interval, 2.55-34.2) for those who started smoking between ages 10 and 19 years and drinking at least three units of alcohol per day. Regarding the joint effects of cumulative amount of smoking and alcohol intake, the risk was high when both smoking and alcohol intake were above a certain level. Conclusions: In this Japanese cohort study, increased cancer mortality risks were observed, especially for people who both started smoking early and drank alcohol. Quitting smoking or not starting to smoke at any age and reducing alcohol consumption are important for preventing esophageal cancer in Japan.

• Journal of Gastric Cancer
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• v.1 no.2
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• pp.113-118
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• 2001

Purpose: The common features of brain metastases from gastric cancer are unknown because brain metastasis is an uncommon pattern of metastasis. The purpose of this study was to investigate the clinical features of and the prognosis for patients with brain metastases after a curative resection for gastric cancer. Materials and Methods: Twenty-one (21) cases of patients with brain metastases of gastric cancer, who had been treated at the Department of Surgery, Yonsei University College of Medicine, were assessed retrospectively. Results: The mean age was $55.8\pm9.6$ years (range: $34\~70$ years), and the male-to-female ratio was 2.5 : .1. The most common neurologic symptom was headache ($38.5\%$), and no patient was free from the neurologic symptoms. The incidence of parenchymal metastasis (PM: $76.2\%$) was higher than that of leptomeningeal metastasis (LM: $19.0\%$). Patients with gastric cancer and brain metastasis showed high rates of blood and lymphatic vessel invasion (lymphatic vessel invasion: $85.7\%$; blood vessel invasion: $80.9\%$). According to Lauren's classification, the incidence of intestinal types was 14/21 ($66.7\%$), that of diffuse types was 3/21 ($14.3\%$) and that of mixed types was 4/21 ($19.0\%$). The mean interval between the gastrectomy and the diagnosis of brain metastasis was $24.7\pm4.0$ months (PM: 26.8 months; LM: 20.3 months). The median period of survival after diagnosis of brain metastasis was 2 months for paren chymal metastasis and 0 months for leptomeningeal metastasis. Conclusion:.. During a follow-up period, patients with neurologic symptoms should be suspected of having brain metastasis. Early diagnosis and treatment is the only hope to prolong survival in such patients.

• Journal of Gastric Cancer
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• v.17 no.3
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• pp.204-211
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• 2017

Purpose: Recently, a nomogram predicting overall survival after gastric resection was developed and externally validated in Korea and Japan. However, this gastric cancer nomogram is derived from large-volume centers, and the applicability of the nomogram in smaller centers must be proven. The purpose of this study is to externally validate the gastric cancer nomogram using a dataset from a medium-volume center in Korea. Materials and Methods: We retrospectively analyzed 610 patients who underwent radical gastrectomy for gastric cancer from August 1, 2005 to December 31, 2011. Age, sex, number of metastatic lymph nodes (LNs), number of examined LNs, depth of invasion, and location of the tumor were investigated as variables for validation of the nomogram. Both discrimination and calibration of the nomogram were evaluated. Results: The discrimination was evaluated using Harrell's C-index. The Harrell's C-index was 0.83 and the discrimination of the gastric cancer nomogram was appropriate. Regarding calibration, the 95% confidence interval of predicted survival appeared to be on the ideal reference line except in the poorest survival group. However, we observed a tendency for actual survival to be constantly higher than predicted survival in this cohort. Conclusions: Although the discrimination power was good, actual survival was slightly higher than that predicted by the nomogram. This phenomenon might be explained by elongated life span in the recent patient cohort due to advances in adjuvant chemotherapy and improved nutritional status. Future gastric cancer nomograms should consider elongated life span with the passage of time.