The relations were examined between colorectal cancer and cigarette smoking and alcohol consumption within the Singapore Chinese Health Study, a population-based, prospective cohort of 63 257 middle-aged and older Chinese men and women enrolled between 1993 and 1998, from whom baseline data on cigarette smoking and alcohol consumption were collected through in-person interviews. By 31 December 2004, 845 cohort participants had developed colorectal cancer (516 colon cancer, 329 rectal cancer). Compared with nondrinkers, subjects who drank seven or more alcoholic drinks per week had a statistically significant, 72% increase in risk of colorectal cancer hazard ratio (HR) ¼ 1.72; 95% confidence interval (CI) ¼ 1.33 -2.22). Cigarette smoking was associated with an increased risk of rectal cancer only. Compared with nonsmokers, HRs (95% CIs) for rectal cancer were 1.43 (1.10 -1.87) for light smokers and 2.64 (1.77 -3.96) for heavy smokers. Our data indicate that cigarette smoking and alcohol use interact in the Chinese population in an additive manner in affecting risk of rectal cancer, thus suggesting that these two exposures may share a common etiologic pathway in rectal carcinogenesis.

Background:Given the close correlation between smoking and alcohol intake in most epidemiologic studies, it is difficult to exclude the residual confounding effect of alcohol in the association between smoking and hepatocellular carcinoma (HCC).Method:We evaluated the association between smoking and risk of HCC in the Singapore Chinese Health Study, a prospective cohort with a low prevalence of alcohol intake. Information on cigarette smoking and alcohol consumption was obtained through in-person interviews conducted at enrolment.Results:After a mean of 11.5 years of follow-up, there were 394 incident cases of HCC. Participants who consumed more than two alcoholic drinks per day showed an increased risk for HCC (hazard ratio (HR)=2.24; 95% confidence interval (CI)=1.46–3.41). After adjusting for alcohol consumption and other potential confounders, current vs never smokers had a statistically significant, increased risk of HCC (HR=1.63; 95% CI=1.27–2.10) that was dose-dependent (number of cigarettes per day, P for trend<0.001). The observed tobacco–HCC association also was duration-dependent (years of smoking in ever smokers, P for trend=0.002). When we excluded daily drinkers from the analysis, all risk estimates remained essentially the same and statistically significant.Conclusion:Our findings strongly implicate tobacco smoke as a causal factor of HCC development.

We investigated the effects of soy isoflavone intake on breast cancer in a prospective study of 35 303 Singapore Chinese women enrolled during April 1993 to December 1998 in the Singapore Chinese Health Study. At recruitment, each subject was personally administered a validated semiquantitative food frequency questionnaire covering 165 food and beverage items. As of December 31 2005, 629 had developed breast cancer following an accumulation of 338 242 person-years. Using Cox regression and adjusting for age at interview, year of interview, dialect group, education, family history of breast cancer, age when periods became regular, parity, menopausal status, body mass index (BMI), n-3 fatty acid, and other covariates, we found breast cancer risk was reduced significantly in association with high soy intake. Relative to women with lower (below median) soy intake (o10.6 mg isoflavone per 1000 Kcal), women with higher (above median) intake showed a significant 18% risk reduction (relative risk (RR) ¼ 0.82, 95% confidence interval (CI) ¼ 0.70 -0.97). This inverse association was apparent mainly in postmenopausal women (RR ¼ 0.74, 95% CI ¼ 0.61 -0.90), and was not observed in premenopausal women (RR ¼ 1.04, 95% CI ¼ 0.77 -1. 40). Among postmenopausal women, the soy -breast cancer association was stronger in those above median BMI (RR ¼ 0.67, 95% CI ¼ 0.51 -0.88) than in leaner women (RR ¼ 0.83, 95% CI ¼ 0.62 -1.11). Duration of follow-up modified the soy -breast cancer association, the effect being twice as large among women with 10 þ vs fewer years of follow-up. Neither oestrogen nor progesterone receptor status of the tumours materially influenced the association. These prospective findings suggest that approximately 10 mg of isoflavones per day, obtained in a standard serving of tofu, may have lasting beneficial effects against breast cancer development. Of at least 28 detailed studies of soy and breast cancer risk published in English since 1990, 14 were in western populations with very low intake of soy (o1 mg of isoflavone per day) and in these, intake was unrelated to breast cancer risk (Wu et al, 2008). Of the other 14 studies in Asia or in Asian -Americans with substantially higher soy intake, eight (Lee et al, 1991;Dai et al, 2001;Yamamoto et al, 2003;Hirose et al, 2005;Lee et al, 2005;Shannon et al, 2005;Do et al, 2007) covered the main sources of soy intake and carefully adjusted for relevant potential confounders. In a meta-analysis of these eight studies, we found a stepwise reduction in breast cancer risk with increasing soy intake. Compared to the lowest soy intake (o5 mg isoflavones per day), risk of breast cancer reduced significantly by 12% in association with moderate intake (B10 mg isoflavones per day) and 29% in association with high intake (20 isoflavones or more per day; Wu et al, 2008). However, only one Asian study was of cohort type (Yamamoto et al, 2003). Assessment of soy intake was incomplete in two other cohort studies (Key et al, 1999;Nishio et al, 2007) and they were not included in our...

An influence of Western diet and lifestyle factors observed among Singapore Chinese may contribute to the population's marked rise in colorectal cancer incidence over the past two decades. Thus far, however, there is little evidence for individual nutrients and foods as major contributing factors in this population. We evaluated whether patterns of food intake were associated with colorectal cancer in a population-based cohort of 61,321 Singapore Chinese that was established in 1993 -98. Two dietary patterns, meat -dim sum and vegetable -fruit -soy, were previously identified by principal components analysis using baseline dietary data from a validated 165-item food frequency questionnaire. As of 31 December 2005, 961 incident colorectal cancer cases were diagnosed. Proportional hazards regression was used to calculate adjusted hazard ratios. Using nearly 10 years of follow-up data, we observed no association with either the meat -dim sum or vegetable -fruit -soy pattern for colorectal cancer. In conclusion, neither individual nutrients or foods nor dietary patterns appear to explain the rise in colorectal cancer among Singapore Chinese population. Trade and Industry, 2005). Along with the rise in industrialisation and urbanisation there was a shift in the major causes of death from infectious diseases to 'lifestyle' diseases common in Western societies, such as cancer, cardiovascular disease, and stroke (Ministry of Health, 2006). This shift was also evident with cancer trends, where cancers associated with infection, such as stomach, nasopharynx, liver, have been decreasing in incidence, whereas cancers of the prostate, breast, and colorectum have been on the rise (Seow et al, 2004). Colorectal cancer, in particular, has increased by over 120% among men and women in the past two decades (Wong and Eu, 2007), approaching the incidence rates seen among US Chinese (McCracken et al, 2007).Using data from a prospective cohort of 63 257 Singapore Chinese, we have investigated diet by analysing associations with individual nutrients and foods thought to be aetiologically relevant to colorectal cancer (World Cancer Research Fund/American Institute for Cancer Research, 2007). While valuable, this strategy probably did not capture the complex interactions between individual nutrients and their correlations with other dietary (Randall et al, 1990;Kant et al, 1991), lifestyle (Slattery et al, 1999;Maskarinec et al, 2000), and sociodemographic patterns (Gex-Fabry et al, 1988;Lv and Cason, 2004) that may confound associations with colorectal cancer. This is one plausible explanation for the more consistent epidemiologic findings with dietary patterns and colorectal cancer, compared to those with nutrients and foods. For example, several prospective studies support a positive association with dietary patterns characterised by red meat, potatoes, sweets, and fried foods (Fung et al, 2003;Dixon et al, 2004;Kesse et al, 2006;Flood et al, 2008). However, few data address dietary patterns among Chinese populations in relation to...

This case -control study of 310 colorectal cancer cases and 1177 controls in a nested prospective, population-based cohort of Singapore Chinese subjects found a statistically significant association between the cyclooxygenase (COX)-2 À765G4C gene polymorphism and colon cancer risk among high consumers of dietary n-6 polyunsaturated fatty acids (odds ratio ¼ 2.38, 95% confidence interval ¼ 1. 23 -4.59 Keywords: cyclooxygenase-2; n-6 polyunsaturated fatty acids; colon cancer; Chinese Diet is believed to be the single most important contributor to colonic carcinogenesis (Tomatis et al, 1990). Experimental data have shown that saturated fatty acids (SFAs) and n-6 polyunsaturated fatty acids (PUFAs) have tumour-enhancing properties in the colon (Reddy and Maeura, 1984;Zhao et al, 1991, Woutersen et al, 1999. Epidemiological data suggest that increased consumption of all meat or red meat, which contains high levels of SFAs, is strongly associated with colorectal cancer (Giovannucci and Goldin, 1997;Sandhu et al, 2001), but there is only limited evidence on the role of dietary n-6 PUFAs (Zock and Katan, 1998;Flood et al, 2003).The putative mechanism through which dietary n-6 PUFAs may enhance colonic carcinogenesis is the increased formation of prostaglandins, with the rate-limiting and committal step being mediated by the cyclooxygenase (COX)-2 enzyme (Dubois et al, 1998). Prostaglandins possess a wide spectrum of procarcinogenic properties (Handler et al, 1990;Cowlen and Eling, 1993;Coffey et al, 1997;Dermott et al, 1999). We therefore hypothesised that functional COX-2 gene polymorphisms may impact on the conversion of n-6 PUFAs into prostaglandins, with consequent change in level of cancer risk. A single nucleotide polymorphism (À765G4C) in the promoter region of the COX-2 gene was recently described (Papafili et al, 2002). We therefore investigated whether this COX-2 gene polymorphism was related to colorectal cancer risk within a population-based, prospective cohort of middle-aged and older Chinese men and women in Singapore. MATERIALS AND METHODS Study subjectsThe study design and subject recruitment of the Singapore Chinese Health Study have been described (Hankin et al, 2001). Briefly, 63 257 Chinese women and men aged 45 -74 years belonging to the Hokkien or Cantonese dialect group were enrolled in the study between April 1993 and December 1998. At recruitment, information on lifestyle factors and usual diet over the last year was obtained through in-person interviews. The dietary component of the questionnaire was validated through a series of 24-h food recalls (Hankin et al, 2001). Respondents were asked to choose from predefined frequency and portion size categories for each of the 165 listed food/beverage items that he/she consumed during the past 12 months. We used the Singapore Food Composition Table to estimate average daily intake of 96 nutrient and nonnutrient compounds for each study subject (Hankin et al, 2001). The Institutional Review Boards at the University of Southern California and the Nation...