• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7497-7500
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• 2013

Background: This study concerns clinical characteristics and survival of renal cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well as the prognostic significance of presenting symptoms. Materials and Methods: The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis. Results: The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, $9.5{\pm}4.3cm$, was larger than non palpable masses, $5.3{\pm}2.7cm$ (p<0.001). Conclusions: This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3747-3752
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• 2015

Background: Colorectal cancer is one of the most commonly occurring cancers in China. Dietary fibre has been thought to decrease the risk of colorectal cancer in Western countries. However, studies investigating the association between dietary fibre (particularly soluble and insoluble fibres) and colorectal cancer have hitherto been lacking in China. Objective: This case-control study examined the effect of dietary fibre intake on the risk of colorectal cancer, stratified by tumour site. Materials and Methods: The study included 265 cases (colon cancer, 105; rectal cancer, 144; colon and rectal cancer, 16) and 252 controls residing in Qingdao. A food frequency questionnaire that included 121 food items was used to collect dietary information. Odds ratio (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression analysis. Results: For food groups, controls in the study consumed more vegetables, soy food and total fibre than did colorectal cancer patients (p<0.05). The intakes of fruit, meat and sea-food did not differ significantly between cases and controls. However, we did not find any association between soy food intake and colon cancer. We observed inverse associations between total fibre intake and colorectal, colon and rectal cancer (Q4 vs Q1: OR=0.44, 95%CI, 0.27-0.73; OR=0.40, 95%CI, 0.21-0.76; OR=0.52, 95%CI, 0.29-0.91). Vegetable fibre intake showed similar inverse associations (Q4 vs Q1: OR=0.51, 95%CI, 0.31-0.85; OR=0.48, 95%CI, 0.25-0.91; OR=0.53, 95%CI, 0.29-0.97). In addition, inverse associations were observed between soluble fibre and insoluble fibre and both colorectal cancer and colon cancer. No relationship was found between colorectal cancer and fruit, soy or grain fibre intakewhen the results were stratified by tumour site. Conclusions: The present study suggests that vegetable fibre and total fibre play very important roles in protecting against colorectal cancer. Soluble and insoluble fibres were inversely associated with only colorectal cancer and colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3769-3772
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• 2013

Background: To investigate the impact of the lymph node ratio (LNR) on the prognosis of patients with locally advanced rectal cancer undergoing pre-operative chemoradiation. Methods: Clinicopathologic and follow up data of 128 patients with stage III rectal cancer who underwent curative resection from 1996 to 2007 were reviewed. The patients were divided into two groups according to the lymph node ratio: LNR ${\leq}$ 0.2 (n=28), and >0.2 (n=100). Kaplan-Meier and the Cox proportional hazard regression models were used to evaluate the prognostic effects according to LNR. Results: Median numbers of lymph nodes examined and lymph nodes involved by tumour were 10.3 (range 2-28) and 5.8 (range 1-25), respectively, and the median LNR was 0.5 (range, 0-1.6). The 5-year survival rate significantly differed by LNR (${\leq}$ 0.2, 69%; >0.2, 19%; Log-rank p value < 0.001). LNR was also a significant prognostic factor of survival adjusted for age, sex, post-operative chemotherapy, total number of examined lymph nodes, metastasis and local recurrence (${\leq}$ 0.2, HR=1; >0.2, HR=4.8, 95%CI=2.1-11.1) and a significant predictor of local recurrence and distant metastasis during follow-up independently of total number of examined lymph node. Conclusions: Total number of examined lymph nodes and LNR were significant prognostic factors for survival in patients with stage III rectal cancer undergoing pre-operative chemoradiotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.539-545
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• 2013

Background: The National Breast Cancer Audit Database of the Society of Breast Surgeons of Australia and New Zealand is used by surgeons to monitor treatment quality and for research. About 60% of early invasive female breast cancers in Australia are recorded. The objectives of this study are: (1) to investigate associations of socio-demographic, health-system and clinical characteristics with treatment of invasive female breast cancer by mastectomy compared with breast conserving surgery; and (2) to consider service delivery implications. Materials and Methods: Bi-variable and multivariable analyses of associations of characteristics with surgery type for cancers diagnosed in 1998-2010. Results: Of 30,299 invasive cases analysed, 11,729 (39%) were treated by mastectomy as opposed to breast conserving surgery. This proportion did not vary by diagnostic year (p>0.200). With major city residence as the reference category, the relative rate (95% confidence limits) of mastectomy was 1.03 (0.99, 1.07) for women from inner regional areas and 1.05 (1.01, 1.10) for those from more remote areas. Low annual surgeon case load (${\leq}10$) was predictive of mastectomy, with a relative rate of 1.08 (1.03, 1.14) when compared with higher case loads. Tumour size was also predictive, with a relative rate of 1.05 (1.01, 1.10) for large cancers (40+ mm) compared with smaller cancers (<30 mm). These associations were confirmed in multiple logistic regression analysis. Conclusions: Results confirm previous studies showing higher mastectomy rates for residents of more remote areas, those treated by surgeons with low case loads, and those with large cancers. Reasons require further study, including possible effects of surgeon and woman's choice and access to radiotherapy services.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1077-1082
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• 2016

Background: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer. Materials and Methods: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22. Results: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy. Conclusions: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2055-2060
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• 2016

Background: Colorectal cancer (CRC) is one of the most common causes of death worldwide and in Thailand. The X-ray repair cross-complementary protein 1 (XRCC1) is required for efficient DNA repair. The effects of this gene on survival in colorectal cancer remain controversial and have not been reported in Thailand. The aim of this study was to investigate the association of the XRCC1 gene with survival of colorectal cancer patients in a Thai population. Materials and Methods: Data and blood samples were collected from 255 newly diagnosed and pathologically confirmed CRC patients who were recruited during the period 2002 to 2006 and whose vital status was followed up until 31 October, 2014. Real-time PCR-HRM was used for genotype identification. The Kaplan-Meier method, the log-rank test, and Cox proportional hazard regression were used to estimate cumulative survival curves and compare various survival distributions and adjusted hazard ratios. Results: Most of the cases were males, and the median age was 55 years. The median survival time was 2.43 years. The cumulative 1-, 3-, 5-, 7-, and 10 year survival rates were 76.70%, 39.25%, 26.50%, 16.60% and 3.56%, respectively. After adjustment, female gender, ages 50-59 and ${\geq}60years$, tumour stage III+IV, a signet-ring cell carcinoma, and poor differentiation had significant associations with increased risk of CRC death. While the XRCC1 Arg/Arg homozygote appeared to be a risk factor for CRC death, the association was not significant. Conclusions: The genetic variant in the XRCC1 may not be associated with the survival of CRC patients in Thailand. Further studies are needed to verify our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2851-2857
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• 2013

Objective: REPS2 plays important roles in inhibiting cell proliferation, migration and in inducing apoptosis of cancer cells, now being identified as a useful biomarker for favorable prognosis in prostate and breast cancers. The purpose of this study was to assess REPS2 expression and to explore its role in esophageal squamous cell carcinoma (ESCC). Methods: Protein expression of REPS2 in ESCCs and adjacent non-cancerous tissues from 120 patients was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, thirty paired ESCC tissues and four ESCC cell lines and one normal human esophageal epithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR and Western blotting. Results: REPS2 mRNA and protein expression levels were down-regulated in ESCC tissues and cell lines. Low protein levels were significantly associated with primary tumour, TNM stage, lymph node metastasis and recurrence (all, P < 0.05). Survival analysis demonstrated that decreased REPS2 expression was significantly associated with shorter overall survival and disease-free survival (both, P < 0.001), especially in early stage ESCC patients. When REPS2 expression and lymph node metastasis status were combined, patients with low REPS2 expression/lymph node (+) had both poorer overall and disease-free survival than others (both, P < 0.001). Cox multivariate regression analysis further revealed REPS2 to be an independent prognostic factor for ESCC patients. Conclusions: Our findings demonstrate that downregulation of REPS2 may contribute to malignant progression of ESCC and represent a novel prognostic marker and a potential therapeutic target for ESCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7097-7103
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• 2014

Over-expression of de novo lipogenesis (DNL) genes is associated with the prognosis of various types of cancers. However, the effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and survival of non-small cell lung cancer (NSCLC) patients after surgery are still unknown. In this study, a total of 500 NSCLC patients who underwent surgery treatment were included. Eight SNPs in 3 genes (ACACA, FASN and ACLY) of the DNL pathway were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards regression and Kaplan-Meier curves were used to analyze the association of SNPs with patient survival and tumour recurrence. We found that two SNPs in the FASN gene were significantly associated with the recurrence of NSCLC. SNP rs4246444 had a significant association with lung cancer recurrence under additive model (hazard ratio [HR], 0.82; 95% confidence interval [95%CI], 0.67-1.00; p=0.05). Under the dominant model, rs4485435 exhibited a significant association with recurrence (HR, 0.75; 95%CI, 0.56-1.01; p=0.05). Additionally, SNP rs9912300 in ACLY gene was significantly associated with overall survival in lung cancer patients (HR, 1.41; 95%CI, 1.02-1.94, p=0.04) under the dominant model. Further cumulative effect analysis showed moderate dose-dependent effects of unfavorable SNPs on both survival and recurrence. Our data suggest that the SNPs in DNL genes may serve as independent prognostic markers for NSCLC patients after surgery.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5923-5931
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• 2015

Background: Registry data from four major public hospitals indicate trends over three decades from 1980 to 2010 in treatment and survival from colorectal cancer with distant metastases at diagnosis (TNM stage IV). Materials and Methods: Kaplan-Meier product-limit estimates and Cox proportional hazards models for investigating disease-specific survival and multiple logistic regression analyses for indicating first-round treatment trends. Results: Two-year survivals increased from 10% for 1980-84 to 35% for 2005-10 diagnoses. Corresponding increases in five-year survivals were from 3% to 16%. Time-to-event risk of colorectal cancer death approximately halved (hazards ratio: 0.48 (0.40, 0.59) after adjusting for demographic factors, tumour differentiation, and primary sub-site. Survivals were not found to differ by place of residence, suggesting reasonable equity in service provision. About 74% of cases were treated surgically and this proportion increased over time. Proportions having systemic therapy and/or radiotherapy increased from 12% in 1980-84 to 61% for 2005-10. Radiotherapy was more common for rectal than colonic cases (39% vs 7% in 2005-10). Of the cases diagnosed in 2005-10 when less than 70 years of age, the percentage having radiotherapy and/or systemic therapy was 79% for colorectal, 74% for colon and 86% for rectum (&RS)) cancers. Corresponding proportions having: systemic therapies were 75%, 71% and 81% respectively; radiotherapy were 24%, 10% and 46% respectively; and surgery were 75%, 78% and 71% respectively. Based on survey data on uptake of offered therapies, it is likely that of these younger cases, 85% would have been offered systemic treatment and among rectum (&RS) cases, about 63% would have been offered radiotherapy. Conclusions: Pronounced increases in survivals from metastatic colorectal cancer have occurred, in keeping with improved systemic therapies and surgical interventions. Use of radiotherapy and/or systemic therapy has increased markedly and patterns of change accord with clinical guideline recommendations.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1403-1407
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• 2015

Background: New tumour biomarkers are being intensely investigated for malignant mesothelioma (MM). Fibulin-3 is produced in MM but its role remains uncertain. The aim of this study was to evaluate the validity of measuring serum fibulin-3 in the diagnosis and prognosis of MM. Materials and Methods: This prospective study was performed on 43 patients and 40 healthy controls who were admitted to our hospital between January 2012 and January 2014. Data from MM patients, including demographic and clinical features, routine laboratory data, levels of serum fibulin-3, and treatment outcomes were defined as potential prognostic factors. The receiver operating characteristic (ROC) curve for fibulin-3 was used to detect the cut-off value with highest sensitivity and specificity. Univariate survival analysis was performed using the Kaplan-Meier method in patients with MM. Afterwards, the possible factors identified with univariate analyses were entered into the cox regression analysis. Results: Our results revealed that patients with MM had significantly higher serum levels of fibulin-3 than controls. The results showed that the best cut-off point was 36.6 ng/ml with an AUC (area under the curve)=0.976, sensitivity=93.0% and specificity=90.0. In our study, the initial significant poor prognostic factors were advanced stage, high white blood cell count, high platelet count, high C-reactive protein (p<0.05 for each variable). Later, according to multivariate analysis the results showed only advanced stage as significant parameter (p=0.040). Conclusions: We determined that real use for serum fibulin-3 was not for prognosis but for diagnosis in MM. Also advanced stage was associated with poor MM prognosis.