Adipokines and the risk of active TB: a nested case-control study.

BACKGROUND: Adipokines are emerging mediators of immune response, and may affect susceptibility to active TB.OBJECTIVE: To examine the associations between adipokines and the risk of active TB.METHODS: In a case-control study nested within a prospective cohort of middle-aged and older adults in Singapore, 280 incident active TB cases who donated blood for research before diagnosis were matched with 280 controls. Serum levels of adiponectin, resistin, leptin and ghrelin were measured. Multivariable logistic regression models were used to compute the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between adipokines and the risk of active TB.RESULTS: Higher levels of leptin and resistin were associated with reduced risk of TB in a dose-dependent manner. Compared to those in the lowest quartile of leptin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.26-0.82; P for trend = 0.009). Similarly, compared to those in the lowest quartile of resistin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.24-0.90; P for trend = 0.03). Adiponectin and ghrelin levels were not associated with TB risk.CONCLUSION: Increased serum levels of leptin and resistin may be associated with reduced susceptibility to active TB infection.

Handgrip Strength and Timed Up-and-Go (TUG) Test are Predictors of Short-Term Mortality among Elderly in a Population-Based Cohort in Singapore.

OBJECTIVES: Asian studies on how physical tests predict short-term mortality in elderly are scarce. We assessed handgrip strength and timed-up-and-go (TUG) as such predictors among elderly Chinese in Singapore. DESIGN: Prospective cohort study. SETTING: Community-dwelling Chinese elderly in Singapore. PARTICIPANTS: We used data from 13,789 subjects in the prospective, population-based Singapore Chinese Health Study, who had a mean age of 74 (range 63 to 97) years at time of measurements. MEASUREMENTS: Subjects underwent assessment for handgrip strength and TUG. They were followed for mortality via linkage with nationwide death registry through 2018. RESULTS: In multivariable analyses, handgrip strength was inversely associated with risk of mortality in a dose-dependent manner: the hazard ratio (HR) [95% confidence interval (CI)] comparing extreme quartiles was 2.05 (1.44-2.90) (Ptrend<0.001). TUG was positively associated with mortality in a stepwise manner: the HR (95% CI) comparing extreme quartiles was 3.08 (2.17-4.38) (Ptrend<0.001). Compared to those with stronger handgrip and faster TUG, participants who either had weaker handgrip or slower TUG had a significant 1.59 to 2.11 fold increase in risk of mortality; while the HR (95% CI) for those who had both weaker handgrip and slower TUG was 3.93 (3.06-5.05). In time-dependent receiver operating characteristic curves, adding handgrip strength and TUG time to a Cox model containing sociodemographic and lifestyle factors, comorbidities, and body measurements significantly improved the area under the curve for the prediction of mortality from 0.5 to 2 years (P≤0.001). CONCLUSION: Among elderly in a Chinese population, handgrip strength and TUG test were strong and independent predictors of short-term mortality.

LncRNA HOST2 enhances gefitinib-resistance in non-small cell lung cancer by down-regulating miRNA-621.

OBJECTIVE: The aim of this study was to clarify whether long non-coding RNA (lncRNA) human ovarian cancer-specific transcript 2 (HOST2) could enhance gefitinib-resistance in non-small cell lung cancer (NSCLC) by down-regulating microRNA-621 (miRNA-621). MATERIALS AND METHODS: The relative expression levels of HOST2, miRNA-621 and SYF2 in NSCLC cell lines were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The regulatory effects of HOST2 and miRNA-621 on the proliferative ability and cell cycle of NSCLC cells were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Meanwhile, the binding relationship between miRNA-621 to HOST2 and SYF2 was verified by Dual-Luciferase reporter gene assay. Furthermore, rescue experiments were conducted to verify whether HOST2 regulated the proliferative ability and cell cycle of NSCLC cells by absorbing miRNA-621 to up-regulate SYF2 level. RESULTS: HOST2 showed significantly greater abundance in gefitinib-resistant PC9 cells (PC9/GR) relative to parental cells. The up-regulation of HOST2 markedly enhanced gefitinib-resistance, the proliferative ability and cell cycle progression of PC9 cells. Subsequent Dual-Luciferase reporter gene assay showed the binding relationship between HOST2 and miRNA-621. Moreover, miRNA-621 was lowly expressed in PC9/GR cells compared with parental cells. Up-regulation of miRNA-621 significantly suppressed the proliferative ability and cell cycle progression, as well as reversed gefitinib-sensitivity of PC9 cells. More importantly, miRNA-621 up-regulation abolished the biological function of HOST2 in NSCLC. SYF2 was confirmed as the target gene of miRNA-621 in the same way. In addition, the overexpression of SYF2 remarkably enhanced gefitinib-resistance, while reversed the inhibitory effects of miRNA-621 on the proliferative ability and cell cycle of NSCLC cells. CONCLUSIONS: HOST2 elevates gefitinib-resistance in NSCLC by degrading miRNA-621 to upregulate SYF2.

Correlation of MiR-152 expression with VEGF expression in placental tissue of preeclampsia rat and its influence on apoptosis of trophoblast cells.

OBJECTIVE: To detect the expression of micro ribonucleic acid (miR)-152 in the placental tissues of preeclampsia (PE) rats and its correlation with the expression of vascular endothelial growth factor (VEGF), and to investigate the influence of miR-152 on the apoptosis of trophoblast cells. MATERIALS AND METHODS: A Sprague Dawley (SD) rat model of PE was established, the total RNA and total protein in the placental tissues were extracted, and reverse transcription-polymerase chain reaction (RT-PCR) was applied to determine the expression level of miR-152 in the placental tissues. The rats were divided into miR-152 high expression group (High group) and miR-152 low expression group (Low group) according to the expression level of miR-152. RT-PCR, immunohistochemistry and Western blotting assay were performed to detect the expressions of VEGF messenger RNA (mRNA) and protein, respectively, in the placental tissues of the two groups of rats. Meanwhile, the BeWo trophoblast cell lines were used in in-vitro experiment, which were divided into Control group and miR-152 mimic group. 10 µL miR-152 mimic were added into each well plate in miR-152 mimic group, and 24 h later, TUNEL staining and flow cytometry were utilized to assess the cell apoptosis in both groups. At the same time, the expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in the two groups of cells were measured using Western blotting assay. RESULTS: The expression level of miR-152 in the placentas of PE rats was increased markedly compared with that of normal rats. The expression levels of VEGF mRNA and protein in the rat placenta in High group were notably higher than those in Low group. In vitro experiment results indicated that miR-152 mimic could promote the apoptosis of BeWo trophoblast cells, up-regulate the pro-apoptotic gene Bax and inhibit the anti-apoptotic gene Bcl-2 simultaneously. CONCLUSIONS: The expression of miR-152 is increased in the placental tissues of PE rats, and it is positively correlated with VEGF. In addition, the increased miR-152 expression can promote the apoptosis of trophoblast cells.

Reproductive factors and risk of total knee replacement due to severe knee osteoarthritis in women, the Singapore Chinese Health Study.

OBJECTIVES: Knee osteoarthritis (OA) is more common in women, and may be related to reproductive or hormonal factors. We evaluated these factors with the risk of total knee replacement (TKR) for severe knee OA among women. METHODS: The Singapore Chinese Health Study recruited 63,257 Chinese aged 45-74 years from 1993 to 1998, and among them, 35,298 were women. Information on height, weight, lifestyle factors, number of biological children, ages at menarche and menopause, and use of hormonal therapies was collected through interviews. Incident cases of TKR were identified via linkage with nationwide database. RESULTS: There were 1,645 women with TKR after mean follow-up of 14.8 years. Higher parity was associated with increased TKR risk in a stepwise manner (P for trend <0.001). Compared to nulliparous women, those with ≥5 children had the highest risk [hazard ratio (HR) 2.01, 95% confidence intervals (CIs) 1.50-2.70]. The effect of parity on TKR risk was significantly stronger among lean women compared to heavier women; HRs (95% CIs) for highest parity was 4.86 (2.22-10.63) for women with body mass index (BMI) <23 kg/m2 and 1.57 (1.14-2.14) for those ≥23 kg/m2 (P for interaction = 0.001). Earlier age at menarche and use of oral contraceptives were significantly associated with TKR in a stepwise manner (P for trend ≤0.002). Age at menopause and use of hormonal therapy were not associated with TKR risk. CONCLUSION: Higher parity, earlier age of menarche and use of oral contraceptives were associated with increased risk of TKR for severe knee OA among women.

Diabetes and body mass index in relation to risk of active tuberculosis: a prospective population-based cohort.

SETTING: Although diabetes (DM) and low body mass index (BMI) are established risk factors for active tuberculosis (TB), the joint effect of type 2 diabetes (T2D) and BMI is unclear.DESIGN: A prospective cohort of 63,257 adults aged 45-74 years were recruited from 1993 to 1998 in Singapore. Active TB cases were identified via linkage with the National TB Registry up to December 2014. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relations of T2D and BMI, independently and jointly, with TB risk.RESULTS: T2D was associated with increased TB risk (HR 2.31, 95% CI 1.93-2.78). Conversely, BMI was inversely associated with TB risk: HR for underweight (BMI < 18.5 kg/m²) was 2.87 (95% CI 2.15-3.82) compared to obese (BMI ≥ 27.5 kg/m²) individuals. Compared to obese individuals without T2D, HR for active TB among underweight individuals with T2D was 8.30 (95% CI 4.43-15.54). There was no statistically significant interaction between BMI and T2D on TB risk (Pinteraction = 0.85).CONCLUSION: Underweight and T2D are independent determinants for active TB. This has important public health implications in Asia where prevalence of tuberculous infection is high, and T2D occurs at lower levels of BMI.

Gout and risk of knee replacement for severe knee osteoarthritis in the Singapore Chinese Health Study.

OBJECTIVE: While cross-sectional and retrospective case-control studies suggest that gout is associated with knee osteoarthritis (KOA), no prospective study has evaluated the risk of total knee replacement (TKR) for KOA in association with gout. We prospectively evaluated the association between gout and the risk of TKR due to severe KOA. DESIGN: We used data from the Singapore Chinese Health Study (SCHS), a prospective cohort with 63,257 Chinese adults aged 45-74 years at recruitment (1993-1998). Self-report of physician-diagnosed gout was enquired at follow-up I interview (1999-2004) from 52,322 subjects. TKR cases for KOA after follow-up I were identified via linkage with nationwide hospital discharge database through 31 December 2011. Multivariable Cox proportional hazards regression model was applied with adjustment for potential risk factors of KOA. RESULTS: Among 51,858 subjects (22,180 men and 29,678 women) included in this analysis, after average 9.7 follow-up years, there were 1,435 cases of TKR. Gout was associated with 39% higher risk of TKR in women [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.08-1.79] but not in men (HR 0.78; 95% CI 0.49-1.23). The positive gout-TKR association in women remained after excluding participants with self-reported history of arthritis (HR 1.57; 95% CI 1.04-2.37). This association was stronger in women who were lean (body mass index [BMI] < 23 kg/m2) (HR 2.17; 95% CI 1.30-3.64) compared to their heavier counterparts (Pinteraction = 0.016). CONCLUSION: Gout is associated with risk of severe KOA, especially in lean women, suggesting the crystal arthritis may play a role in the pathogenesis or progression of OA.

Association between change in body weight after midlife and risk of hip fracture-the Singapore Chinese Health Study.

UNLABELLED: The relationship between change in body weight and risk of fractures is inconsistent in epidemiologic studies. In this cohort of middle-aged to elderly Chinese in Singapore, compared to stable weight, weight loss ≥10 % over an average of 6 years is associated with nearly 40 % increase in risk of hip fracture. INTRODUCTION: Findings on the relationship between change in body weight and risk of hip fracture are inconsistent. In this study, we examined this association among middle-aged and elderly Chinese in Singapore. METHODS: We used prospective data from the Singapore Chinese Health Study, a population-based cohort of 63,257 Chinese men and women aged 45-74 years at recruitment in 1993-1998. Body weight and height were self-reported at recruitment and reassessed during follow-up interview in 1999-2004. Percent in weight change was computed based on the weight difference over an average of 6 years, and categorized as loss ≥10 %, loss 5 to <10 %, loss or gain <5 % (stable weight), gain 5 to <10 %, and gain ≥10 %. Multivariable Cox proportional hazards regression model was applied with adjustment for risk factors for hip fracture and body mass index (BMI) reported at follow-up interview. RESULTS: About 12 % experienced weight loss ≥10 %, and another 12 % had weight gain ≥10 %. After a mean follow-up of 9.0 years, we identified 775 incident hip fractures among 42,149 eligible participants. Compared to stable weight, weight loss ≥10 % was associated with 39 % increased risk (hazard ratio 1.39; 95 % confidence interval 1.14, 1.69). Such elevated risk with weight loss ≥10 % was observed in both genders and age groups at follow-up (≤65 and >65 years) and in those with baseline BMI ≥20 kg/m(2).There was no significant association with weight gain. CONCLUSIONS: Our findings provide evidence that substantial weight loss is an important risk factor for osteoporotic hip fractures among the middle-aged to elderly Chinese.

Association between body mass index and risk of total knee replacement, the Singapore Chinese Health Study.

PURPOSE: Data on the association between body mass index (BMI) and risk of knee osteoarthritis (KOA) are sparse for Asian populations who are leaner than Western populations. We evaluated the association between BMI and risk of total knee replacement (TKR) due to severe KOA among Chinese in Singapore. METHODS: We used data from the Singapore Chinese Health Study (SCHS), a population-based prospective cohort of 63,257 Chinese men and women, aged 45-74 years at enrollment from 1993 to 1998. Information on height, weight, diet and lifestyle factors were obtained via in-person interviews. TKR cases for severe KOA were identified via linkage with the nationwide hospital discharge database through 2011. Cox regression and weighted least squares regression were used in the analysis. RESULTS: The mean BMI among cohort participants was 23.1 kg/m(2), and more than two-thirds had BMI below 25 kg/m(2). A total of 1649 had TKR attributable to severe KOA. Risk of TKR increased in a strong dose-dependent manner with increasing BMI throughout the 15-32 kg/m(2) range and became less clear at BMI >32 kg/m(2). In the BMI range 16-27 kg/m(2), there was a 27% increase in TKR risk for each unit increase in BMI (P for trend < 0.001). Compared to BMI 19-20 kg/m(2), the risk estimates of TKR were all statistically significant with increasing unit of BMI ≥21 kg/m(2). Results were similar for men and women. CONCLUSION: Our results provided evidence for a constant mechanical mechanism underlying BMI and KOA initiation and/or progression.

Diabetes mellitus and risk of hepatocellular carcinoma: findings from the Singapore Chinese Health Study.

BACKGROUND: The increasing prevalence of diabetes may contribute to the rising incidence of hepatocellular carcinoma (HCC) in the US and other developed countries where HCC incidence is relatively low. Data from prospective studies on diabetes and risk of HCC in at-risk populations due to high prevalence of viral hepatitis in southeast Asia are sparse. METHODS: The Singapore Chinese Health Study is a prospective cohort of 63, 257 middle-aged and older Chinese men and women enrolled in 1993-1998. Besides an in-person interview administered to all participants at baseline, testing of serologic markers of hepatitis B or C infections were performed on a subset of cohort subjects. After a mean follow-up of 14 years, 499 cohort participants developed HCC. RESULTS: A history of diabetes at baseline was associated with a hazard ratio of 2.14 (95% confidence interval, 1.69-2.71). This statistically significant association was comparable in magnitude between men and women, and remained equally strong across strata of subjects defined by the number of years between their first clinical diagnosis of diabetes and time of enrollment in this cohort. Within a nested case-control set of cohort subjects tested for serological markers of hepatitis B or C infections, the diabetes-HCC association was found to be present mainly among those devoid of any markers. CONCLUSION: A history of diabetes at baseline is highly associated with non-viral HCC. Future studies are warranted to elucidate the biological mechanism underpinning the role of diabetes in nonviral-related hepatocarcinogenesis.

Dietary B vitamin intake and risk of hip fracture: the Singapore Chinese Health Study.

UNLABELLED: This prospective cohort study that comprehensively examined effects of different B vitamins in an Asian population showed an inverse relationship between dietary intake of pyridoxine and hip fracture risk in elderly women. These findings suggest that maintaining sufficient pyridoxine intake may be beneficial in preserving bone health in postmenopausal women. INTRODUCTION: B vitamins have recently been investigated for their possible roles in maintaining bone health. Incidence of osteoporotic hip fracture has been rising in Asia, but epidemiological data on dietary B vitamins and risk of osteoporotic fractures are sparse. We aimed to examine the association between dietary intakes of B vitamins (thiamin, riboflavin, niacin, pyridoxine, folate, and cobalamin) and hip fracture risk among elderly Chinese in Singapore. METHODS: The current study was conducted in the Singapore Chinese Health Study, which is a population-based cohort prospective study that enrolled a total of 63,257 men and women aged 45-74 years between 1993 and 1998. Dietary intakes of B vitamins were derived from a validated food frequency questionnaire and the Singapore Food Composition Database. RESULTS: After a mean follow-up period of 13.8 years, 1,630 hip fracture incident cases were identified. A statistically significant inverse relationship between dietary pyridoxine intake and hip fracture risk was observed among women (p for trend = 0.002) but not among men. Compared to women in the lowest quartile intake (0.37-0.61 mg/1,000 kcal/day), women in the highest quartile intake (0.78-1.76 mg/1,000 kcal/day) had a 22 % reduction in hip fracture risk (hazard ratio 0.78, 95 % confidence interval 0.66-0.93). Dietary intakes of the other B vitamins of interest were not related to hip fracture risk. CONCLUSIONS: Our findings suggest that maintaining adequate intake of pyridoxine may prevent osteoporotic fractures among elderly women.

All-cause and cause-specific mortality after hip fracture among Chinese women and men: the Singapore Chinese Health Study.

UNLABELLED: All-cause mortality risk persisted for 5 years after hip fractures in both men and women. There may be gender-specific differences in effect and duration of excess risk for cause-specific mortality after hip fracture. INTRODUCTION: To determine all-cause and cause-specific mortality risk in the first 5 years after hip fracture in an Asian Chinese population. METHODS: The Singapore Chinese Health Study is a population-based cohort of 63,257 middle-aged and elderly Chinese men and women in Singapore recruited between 1993 and 1998. This cohort was followed up for hip fracture and death via linkage with nationwide hospital discharge database and death registry. As of 31 December 2008, we identified 1,166 hip fracture cases and matched five non-fracture cohort subjects by age and gender for each fracture case. Cox proportional hazards and competing risks regression models with hip fracture as a time-dependent covariate were used to determine all-cause and cause-specific mortality risk, respectively. RESULTS: Increase in all-cause mortality risk persisted till 5 years after hip fracture (adjusted hazard ratio, aHR = 1.58 [95 % CI, 1.35-1.86] for females and aHR = 1.64 [95 % CI, 1.30-2.06] for males). Men had higher mortality risk after hip fracture than women for deaths from stroke and cancer up to 1 year post-fracture but women with hip fracture had higher coronary artery mortality risk than men for 5 years post-fracture. Men had higher risk of death from pneumonia while women had increased risk of death from urinary tract infections. There was no difference in mortality risk by types of hip fracture surgery. CONCLUSIONS: All-cause mortality risk persisted for 5 years after hip fractures in men and women. There are gender-specific differences in effect size and duration of excess mortality risk from hip fractures between specific causes of death.

Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study.

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.

Plasma carotenoids and risk of acute myocardial infarction in the Singapore Chinese Health Study.

BACKGROUND AND AIM: Modification of low-density lipoprotein due to oxidative stress is essential in the development of coronary atherosclerosis. Data of specific carotenoids except ß-carotene on cardioprotective effects in humans are limited. METHODS AND RESULTS: This study examined the associations between plasma concentrations of specific carotenoids and incidence of acute myocardial infarction. The study included 280 incident cases of acute myocardial infarction and 560 matched controls nested within the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women aged 45-74 years old enrolled in 1993-1998 in Singapore. Retinol and carotenoids in prediagnostic plasma were quantified using high-performance liquid chromatography. High levels of plasma ß-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction after adjustment for multiple risk factors for coronary heart disease. For ß-cryptoxanthin, the odds ratio (95% confidence interval) for the highest (Q5) versus the lowest (Q1) quintile was 0.67 (0.37-1.21) (P for trend=0.03). For lutein, the odds ratios (95% confidence intervals) for the combined Q2-Q3 and the combined Q4-Q5 versus Q1 were 0.71 (0.45-1.12) and 0.58 (0.35-0.94) respectively (P for trend=0.03). There was no statistically significant association between other carotenoids or retinol and risk of acute myocardial infarction. CONCLUSIONS: High plasma levels of ß-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction. The findings of this study support a cardioprotective role of these two carotenoids in humans.

Body mass index and smoking-related lung cancer risk in the Singapore Chinese Health Study.

BACKGROUND: Smokers with low body mass index (BMI) may be more susceptible to lung cancer. METHODS: We prospectively examined the association between baseline BMI and lung cancer risk in the Singapore Chinese Health Study, a cohort of 63 257 Chinese enrolled between 1993 and 1998. RESULTS: After adjustment for smoking intensity and duration, BMI was inversely associated with risk of lung cancer among current smokers (P for trend=0.0004). Current smokers at different dosage of smoking with low BMI had significantly higher risk for lung cancer than those with high BMI. Hazard ratios (95% confidence intervals) of lung cancer for heavy smokers with BMI of > or =28, 24-<28, 20-<24, and <20 kg m(-2) were 6.37 (2.10-19.30), 9.01 (5.04-16.10), 8.53 (6.35-11.5), and 11.12 (6.60-18.70), respectively, as compared with nonsmokers. BMI had no modifying effects on lung cancer risk among nonsmokers and former smokers. CONCLUSION: Smokers with lower BMI may experience an enhanced risk of lung cancer. The findings have significant public-health implication given the increase in smoking prevalence in developing countries, where people still have relatively low BMI.

Urinary tract infections and reduced risk of bladder cancer in Los Angeles.

We investigated the association between urinary tract infections (UTIs) and transitional cell carcinoma of the bladder in a population-based case-control study in Los Angeles covering 1586 cases and age-, gender-, and race-matched neighbourhood controls. A history of bladder infection was associated with a reduced risk of bladder cancer among women (odds ratio (OR), 0.66; 95% confidence interval (CI), 0.46-0.96). No effect was found in men, perhaps due to power limitations. A greater reduction in bladder cancer risk was observed among women with multiple infections (OR, 0.37; 95% CI, 0.18-0.78). Exclusion of subjects with a history of diabetes, kidney or bladder stones did not change the inverse association. A history of kidney infections was not associated with bladder cancer risk, but there was a weak association between a history of other UTIs and slightly increased risk among men. Our results suggest that a history of bladder infection is associated with a reduced risk of bladder cancer among women. Cytotoxicity from antibiotics commonly used to treat bladder infections is proposed as one possible explanation.

Cigarettes and alcohol in relation to colorectal cancer: the Singapore Chinese Health Study.

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)=1.72; 95% confidence interval (CI)=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.

Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review.

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10-20%) than among Asians (50-60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.