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Koh W.-P.,National University of Singapore | Nelson H.H.,University of Minnesota | Yuan J.-M.,University of Minnesota | van den Berg D.,University of Southern California | And 3 more authors.

Cigarette smoking is a risk factor for colorectal cancer. Putative colorectal procarcinogens in tobacco smoke include polycyclic aromatic hydrocarbons and heterocyclic aromatic amines that are known substrates of glutathione S-transferases (GSTs). This study examined the influence of functional GST gene polymorphisms on the smoking-colorectal cancer association in a population known to be minimally exposed to dietary sources of these procarcinogens. Incident cases of colorectal cancer (n = 480) and matched controls (n = 1167) were selected from the Singapore Chinese Health Study, a population-based prospective cohort of 63 257 men and women who have been followed since 1993. We determined the deletion polymorphisms of GSTM1 and GSTT1 and the functional polymorphism at codon 105 of GSTP1 for each subject. A three level composite GST index was used to examine if GST profile affected a smoker's risk of developing colorectal cancer. While there was no statistically significant association between cigarette smoking and colorectal cancer risk among subjects absent of any at-risk GST genotypes, smokers possessing two to three at-risk GST genotypes exhibited a statistically significant increased risk of colorectal cancer compared with nonsmokers (P = 0.0002). In this latter stratum, heavy smokers exhibited a >5-fold increased risk relative to never-smokers (odds ratio, 5.43; 95% confidence interval, 2.22-13.23). Subjects with one at-risk GST genotype displayed a statistically significant but weaker association with smoking. These findings suggest that GST gene polymorphisms influence interindividual susceptibility to smoking-associated colorectal cancer. Our data indicate an important role for GST enzymes in the detoxification of colorectal carcinogens in tobacco smoke. © The Author 2011. Published by Oxford University Press. All rights reserved. Source

Koh W.-P.,National University of Singapore | Van Den Berg D.,University of Southern California | Jin A.,National Registry of Diseases Office | Wang R.,University of Minnesota | And 2 more authors.
Breast Cancer Research and Treatment

The MDM2 oncoprotein regulates the p53 pathway and, while functional polymorphisms of the MDM2 and p53 genes have been investigated for association with breast cancer risk, results are largely null or non-conclusive. We have earlier reported that the increased intake of soy isoflavones reduces risk of postmenopausal breast cancer, and experimental studies suggest that dietary isoflavones can down-regulate the expression of the MDM2 oncoprotein. In this study, we investigated the association between the MDM2 SNP309 and TP53 R72P polymorphisms and breast cancer risk using a case-control study of 403 cases and 662 controls nested among 35,303 women in The Singapore Chinese Health Study, a population-based, prospective cohort of middle-aged and elderly men and women who have been continuously followed since 1993. The G allele of the TP53 R72P polymorphism and T allele of the MDM2 SNP309 polymorphism were putative high-risk alleles and exhibited a combined gene-dose-dependent joint effect on breast cancer risk that was more clearly observed in postmenopausal women. Among postmenopausal women, the simultaneous presence of G allele in TP53 and T allele in MDM2 polymorphisms was associated with an odds ratio (OR) of 2.42 [95% confidence interval (CI) 1.06-5.50]. Furthermore, the protective effect of dietary soy isoflavones on postmenopausal breast cancer was mainly confined to women homozygous for the high activity MDM2 allele (GG genotype). In this genetic subgroup, women consuming levels of soy isoflavones above the median level exhibited risk that was half of those with below median intake (OR 0.52; 95% CI 0.28-0.99). Our findings support experimental data implicating combined effects of MDM2 protein and the p53-mediated pathway in breast carcinogenesis, and suggest that soy isoflavones may exert protective effect via down-regulation of the MDM2 protein. © 2011 Springer Science+Business Media, LLC. Source

Lim G.H.,National Registry of Diseases Office | Lim G.H.,Health Services Research and Evaluation Division | Chow K.Y.,National Registry of Diseases Office | Lee H.P.,National University of Singapore
Singapore Medical Journal

In this review, we examine the trends in cancer incidence, mortality and survival in the last decade, using published data from the Singapore Cancer Registry in the period 1998 to 2009. While overall cancer incidences have remained stable, overall cancer mortality rates have declined for both genders. Thus, it is not surprising that there was an improvement in cancer survival. A steady decrease in lung cancer among males and females was observed, thereby leading to a drop in its cancer ranking. In the last five years, the most frequently occurring cancer was colorectal cancer among the male population and breast cancer among females. Survival for both cancers remained relatively optimistic. There is good reason to pay special attention to colorectal cancer due to its high frequency of occurrence among the Singapore population and because it is amenable to early detection via screening. Source

Loy E.Y.,National Registry of Diseases Office
Annals of the Academy of Medicine, Singapore

The aim of this study is to investigate the risk of cancer among end-stage renal disease (ESRD) patients on dialysis in Singapore. The study looks at a retrospective cohort of 5505 ESRD patients who had received dialysis between 1998 and 2007. The cancer risk of these patients would be compared against the risk of the general population. During a median follow-up time of 3.9 years, 267 (4.9%) dialysis patients developed cancer. The risk of cancer (excluding non-melanoma skin cancer) is 1.66 times higher in dialysis patients than the general population, and is highest at age less than 35 years old and at first year after dialysis. Cancer risk was found to be significantly higher among Chinese dialysis patients, followed by Malays, compared to the general population. The 3 sites with highest elevated cancer risks among dialysis patients compared to the general population are kidney, tongue and multiple myeloma. The finding of elevated cancer risk among younger dialysis patients is similar to other international studies. High cancer risks among specific cancer sites were also consistent with other studies. In view of the lack of screening procedures for these cancers and shortened expected survival of ESRD patients, cancer screening of ESRD patients should be individualised and based on a reasonable life expectancy and transplant candidacy, keeping in mind the competing risk of cardiovascular mortality. Source

Ainslie-Waldman C.E.,University of Minnesota | Koh W.-P.,National University of Singapore | Jin A.,National Registry of Diseases Office | Yeoh K.G.,National University of Singapore | And 4 more authors.
Cancer Epidemiology Biomarkers and Prevention

Background: Despite experimental evidence showing chemopreventive effects of coffee-related compounds on gastric carcinogenesis, epidemiologic studies generally do not support coffee-gastric cancer associations. Observational data are lacking among high-risk populations with sufficient regular coffee consumption. Methods: We examined the association between caffeinated coffee intake and gastric cancer risk in a population-based cohort that enrolled 63,257 Chinese men and women ages 45 to 74 years between 1993 and 1998 in Singapore. Incident gastric cancer cases (n = 647) were identified after a mean follow-up of 14.7 years. Biomarkers of Helicobacter pylori (H. pylori) infection were measured in a subset of gastric cancer cases with blood collected before cancer diagnosis and their matched controls. Results: In the total cohort, daily versus nondaily coffee intake was associated with a statistically nonsignificant decrease in gastric cancer risk [HR = 0.85; 95% confidence interval (CI), 0.69-1.04]. In women, the inverse association strengthened and reached statistical significance (HR = 0.63; 95% CI, 0.46-0.87). In analyses restricted to never smokers and nondrinkers of alcohol, inverse associations strengthened in the total cohort (HR = 0.69; 95% CI, 0.52-0.91) and in women (HR = 0.52; 95% CI, 0.37-0.74). There was no coffee-gastric cancer risk association among men, regardless of smoking status or alcohol consumption. Similar results were observed in the nested case-control study after adjustment for H. pylori infection. Conclusion: Daily coffee consumption may reduce the risk of gastric cancer in high-risk populations, especially among women. Impact: Research aimed at identifying the compounds in coffee that may protect against gastric carcinogenesis is warranted. © 2014 AACR. Source

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