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1.  Vitamin Intake and Liver Cancer Risk: A Report From Two Cohort Studies in China 
Correspondence to: Xiao-Ou Shu, MD, PhD, Vanderbilt Epidemiology Center, 2525 West End Ave, Ste 600 (IMPH), Nashville, TN 37203-1738 (e-mail: xiao-ou.shu@vanderbilt.edu) and Yong-Bing Xiang, MD, MSc, Shanghai Cancer Institute, No. 25, Lane 2200, Xie Tu Road, Shanghai 200032, People’s Republic of China (e-mail: ybxiang@shsci.org).Background
Epidemiologic studies on the relationship between vitamin intake and liver cancer risk are sparse and inconsistent.
Methods
We evaluated vitamin intake from diet and supplements and risk of liver cancer in 132 837 women and men from China who were recruited into the Shanghai Women’s Health Study from 1997 to 2000 or the Shanghai Men’s Health Study from 2002 to 2006. In-person interviews, using a validated food-frequency questionnaire, were conducted to collect data on dietary habits. Follow-up consisted of in-person surveys and record linkage. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazard models with adjustment for potential confounders to compare liver cancer risk among participants with high vs low vitamin intake. All statistical tests were two-sided.
Results
After excluding the first 2 years of follow-up, 267 participants (including 118 women and 149 men) developed liver cancer during an average of 10.9 (Shanghai Women’s Health Study) or 5.5 (Shanghai Men’s Health Study) years of follow-up. Dietary vitamin E intake was inversely associated with liver cancer risk (P trend = .01), as was vitamin E supplement use (hazard ratio = 0.52, 95% confidence interval = 0.30 to 0.90). This association was consistent among participants with and without self-reported liver disease or a family history of liver cancer. Vitamin C and multivitamin use was associated with increased risk among participants with self-reported liver disease or family history of liver cancer, whereas intake of vitamin C and other vitamins from dietary sources was unrelated to liver cancer risk.
Conclusions
Vitamin E intake, either from diet or supplements, may reduce the risk of liver cancer.
doi:10.1093/jnci/djs277
PMCID: PMC3611811  PMID: 22811438
2.  Association of Obesity-related Genetic Variants With Endometrial Cancer Risk: A Report From the Shanghai Endometrial Cancer Genetics Study 
American Journal of Epidemiology  2011;174(10):1115-1126.
Obesity is a well-established risk factor for endometrial cancer, the most common gynecologic malignancy. Recent genome-wide association studies (GWAS) have identified multiple genetic markers for obesity. The authors evaluated the association of obesity-related single nucleotide polymorphisms (SNPs) with endometrial cancer using GWAS data from their recently completed study, the Shanghai Endometrial Cancer Genetics Study, which comprised 832 endometrial cancer cases and 2,049 controls (1996–2005). Thirty-five SNPs previously associated with obesity or body mass index (BMI; weight (kg)/height (m)2) at a minimum significance level of ≤5 × 10−7 in the US National Human Genome Research Institute's GWAS catalog (http://genome.gov/gwastudies) and representing 26 unique loci were evaluated by either direct genotyping or imputation. The authors found that for 22 of the 26 unique loci tested (84.6%), the BMI-associated risk variants were present at a higher frequency in cases than in population controls (P = 0.0003). Multiple regression analysis showed that 9 of 35 BMI-associated variants, representing 7 loci, were significantly associated (P ≤ 0.05) with the risk of endometrial cancer; for all but 1 SNP, the direction of association was consistent with that found for BMI. For consistent SNPs, the allelic odds ratios ranged from 1.15 to 1.29. These 7 loci are in the SEC16B/RASAL, TMEM18, MSRA, SOX6, MTCH2, FTO, and MC4R genes. The associations persisted after adjustment for BMI, suggesting that genetic markers of obesity provide value in addition to BMI in predicting endometrial cancer risk.
doi:10.1093/aje/kwr233
PMCID: PMC3246689  PMID: 21976109
body mass index; endometrial neoplasms; genetics; genome-wide association study; obesity; risk factors
3.  Association of Hormone-Related Characteristics and Breast Cancer Risk by Estrogen Receptor/Progesterone Receptor Status in the Shanghai Breast Cancer Study 
American Journal of Epidemiology  2011;174(6):661-671.
Etiologic differences between subtypes of breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status are not well understood. The authors evaluated associations of hormone-related factors with breast cancer subtypes in a population-based case-control study involving 1,409 ER-positive (ER+)/PR-positive (PR+) cases, 712 ER-negative (ER−)/PR-negative (PR−) cases, 301 ER+/PR− cases, 254 ER−/PR+ cases, and 3,474 controls aged 20–70 years in Shanghai, China (phase I, 1996–1998; phase II, 2002–2005). Polytomous logistic regression and Wald tests for heterogeneity across subtypes were conducted. Breast cancer risks associated with age at menarche, age at menopause, breastfeeding, age at first livebirth, waist-to-hip ratio, and oral contraceptive use did not differ by hormone receptor status. Among postmenopausal women, higher parity (≥2 children vs. 1) was associated with reduced risk (odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.52, 0.91) and higher body mass index (BMI; weight (kg)/height (m)2) with increased risk (highest quartile: OR = 2.40, 95% CI: 1.65, 3.47) of the ER+/PR+ subtype but was unrelated to the ER−/PR− subtype (for parity, Pheterogeneity = 0.02; for BMI, Pheterogeneity < 0.01). Hormone replacement therapy (OR = 2.25, 95% CI: 1.40, 3.62) and alcohol consumption (OR = 1.59, 95% CI: 1.01, 2.51) appeared to be preferentially associated with the ER+/PR− subtype. These findings indicate that BMI, parity, hormone replacement therapy, and alcohol consumption may play different roles in subtypes of breast cancer. More research is needed to better understand the etiology of 2 relatively rare subtypes, ER+/PR− tumors and ER−/PR+ tumors.
doi:10.1093/aje/kwr145
PMCID: PMC3166707  PMID: 21768404
breast neoplasms; China; hormones; receptors, estrogen; receptors, progesterone; risk factors; women
4.  Evaluation of Genetic Susceptibility Loci for Obesity in Chinese Women 
American Journal of Epidemiology  2010;172(3):244-254.
Recent genome-wide association (GWA) studies have identified 18 genetic loci for obesity. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996–2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct obesity loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the FTO, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)2), body weight, and the prevalence of obesity. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for obesity ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of obesity. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of obesity than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations.
doi:10.1093/aje/kwq129
PMCID: PMC2917056  PMID: 20616199
body mass index; genome-wide association study; linkage disequilibrium; obesity; polymorphism, genetic; women
5.  The Effect of Regular Exercise on Quality of Life Among Breast Cancer Survivors 
American Journal of Epidemiology  2009;170(7):854-862.
The authors evaluated the effect of regular exercise during the first 36 months after cancer diagnosis on quality of life (QOL) in a population-based cohort study of 1,829 Chinese women diagnosed with breast cancer. The women were identified between 2002 and 2004 and were invited to participate in the study about 6 months after cancer diagnosis. Exercise was assessed approximately 6, 18, and 36 months after diagnosis, and a metabolic equivalent task (MET) score in hours per week was derived. A cumulative, weighted exercise-MET score was created for regular exercise during the 36-month postdiagnosis period. QOL was evaluated at 6 and 36 months postdiagnosis. Multiple linear regression and mixed models were conducted to evaluate the association between regular exercise and QOL, with adjustment for clinical prognostic factors and other potential confounders. Both exercise-MET scores measured during the first 6 or 36 months postdiagnosis and the weighted exercise-MET score over the 36-month postdiagnosis period were positively associated with total QOL score and physical, psychological, and social well-being scores assessed at 36 months postdiagnosis (all P for trend < 0.05). Compared with nonregular exercisers, women with higher exercise-MET scores (≥8.3 MET-hours/week) were more likely to have higher scores for total QOL and specific QOL domains (all P < 0.05). The exercise-QOL association remained stable over time after cancer diagnosis. This study suggests that regular exercise after breast cancer diagnosis improves QOL.
doi:10.1093/aje/kwp209
PMCID: PMC2765358  PMID: 19696227
breast neoplasms; cohort studies; exercise; quality of life
6.  Intakes of Fruits, Vegetables, and Related Vitamins and Lung Cancer Risk: Results from the Shanghai Men's Health Study (2002–2009) 
Nutrition and cancer  2013;65(1):51-61.
Most epidemiological studies evaluating the association of fruit and vegetable intakes on lung cancer risk were conducted in North American and European countries. We investigated the association of intakes of fruits, vegetables, dietary vitamins A and C, and folate with lung cancer risk among 61,491 Chinese adult men who were recruited to the Shanghai Men's Health Study, a population-based, prospective cohort study. Baseline dietary intake was assessed through a validated food frequency questionnaire during in-home visits. Multivariate Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of lung cancer risk associated with dietary intakes. During a median follow-up of 5.5 years, 359 incident lung cancer cases accrued after the first year of follow-up and 68.8% of them were current smokers. Intakes of green leafy vegetables, β-carotene-rich vegetables, watermelon, vitamin A, and carotenoids were inversely associated with lung cancer risk; the corresponding HR (95% CI) comparing the highest with the lowest quartiles were 0.72 (0.53–0.98), 0.69 (0.51–0.94), 0.65 (0.47–0.90), 0.63 (0.44–0.88), and 0.64 (0.46–0.88). Intake of all fruits and vegetables combined was marginally associated with lower risk. Our study suggests that the consumption of carotenoid-rich vegetables is inversely associated with lung cancer risk.
doi:10.1080/01635581.2013.741757
PMCID: PMC3787870  PMID: 23368913
fruits; vegetables; carotenoids; dietary intake; lung cancer; epidemiological
7.  Obesity and Weight Change in Relation to Breast Cancer Survival 
The authors evaluated the prognostic effects of obesity and weight change after breast cancer diagnosis. A total of 5042 breast cancer patients aged 20–75 were identified through the population-based Shanghai Cancer Registry approximately 6 months after cancer diagnosis and recruited into the study between 2002 and 2006. Participants were followed by in-person interviews supplemented by record linkage with the Shanghai Vital Statistics Registry database. Anthropometric measurements were taken and information on sociodemographic, clinical, and lifestyle factors was collected through in-person interviews. During the median follow-up of 46 months, 442 deaths and 534 relapses/breast cancer-specific deaths were documented. Women with body mass index (BMI) ≥30 at diagnosis had higher mortality than women with 18.5≤BMI<25; the multivariate adjusted hazard ratios (HRs) were 1.55 (95% confidence interval (95% CI): 1.10–2.17) for total mortality and 1.44 (95% CI: 1.02–2.03) for relapse/disease-specific mortality. Similar results were found for pre- and post-diagnostic obesity. Women who gained ≥5kg or lost >1kg had higher mortality than those who maintained their weight. No association was observed between waist-to-hip ratio and mortality. Our study suggests that obesity and weight change after diagnosis are inversely associated with breast cancer prognosis. Weight control is important among women with breast cancer.
doi:10.1007/s10549-009-0708-3
PMCID: PMC3777404  PMID: 20058068
Body mass index; central obesity; weight change; breast cancer; survival
8.  Polycyclic aromatic hydrocarbons: determinants of urinary 1-hydroxypyrene glucuronide concentration and risk of colorectal cancer in the Shanghai Women’s Health Study 
BMC Cancer  2013;13:282.
Background
Associations between polycyclic aromatic hydrocarbons (PAHs) and colorectal cancer have been reported previously but few studies have characterized PAH exposure using biological measurements. We evaluated colorectal cancer risk in relation to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG), a polycyclic aromatic hydrocarbon (PAH) metabolite, and assessed determinants of PAH exposure among controls in the Shanghai Women’s Health Study (SWHS).
Methods
Concentrations of 1-OHPG were measured in spot urine samples collected from 343 colorectal cancer cases and 343 individually matched controls. Questionnaires were administered to collect information on demographic characteristics and reported exposures. Odds ratios were calculated for risk of colorectal cancer in relation to quartiles of urinary 1-OHPG concentration. Potential determinants of natural log-transformed urinary 1-OHPG concentration were evaluated among a combined sample of controls from this study and another nested case–control study in the SWHS (Ntotal=652).
Results
No statistically significant differences in risk of colorectal cancer by urinary 1-OHPG levels were observed. Among controls, the median (interquartile range) urinary 1-OHPG concentration was 2.01 pmol/mL (0.95-4.09). Active and passive smoking, using coal as a cooking fuel, eating foods that were cooked well done, and recent consumption of fried dough (e.g., yóutiáo) were associated with elevated levels of 1-OHPG, though only active smoking and fried dough consumption achieved statistical significance in multivariate analyses.
Conclusions
This study does not provide evidence of an association between urinary levels of 1-OHPG and risk of colorectal cancer among women. Several environmental and dietary sources of PAH exposure were identified. Overall, the levels of 1-OHPG in this population of predominantly non-smoking women were considerably higher than levels typically observed among non-smokers in Europe, North America, and other developed regions.
doi:10.1186/1471-2407-13-282
PMCID: PMC3686696  PMID: 23758680
1-hydroxypyrene glucuronide; Polycyclic aromatic hydrocarbons; Colorectal cancer; China
9.  Exome sequencing generates high quality data in non-target regions 
BMC Genomics  2012;13:194.
Background
Exome sequencing using next-generation sequencing technologies is a cost efficient approach to selectively sequencing coding regions of human genome for detection of disease variants. A significant amount of DNA fragments from the capture process fall outside target regions, and sequence data for positions outside target regions have been mostly ignored after alignment.
Result
We performed whole exome sequencing on 22 subjects using Agilent SureSelect capture reagent and 6 subjects using Illumina TrueSeq capture reagent. We also downloaded sequencing data for 6 subjects from the 1000 Genomes Project Pilot 3 study. Using these data, we examined the quality of SNPs detected outside target regions by computing consistency rate with genotypes obtained from SNP chips or the Hapmap database, transition-transversion (Ti/Tv) ratio, and percentage of SNPs inside dbSNP. For all three platforms, we obtained high-quality SNPs outside target regions, and some far from target regions. In our Agilent SureSelect data, we obtained 84,049 high-quality SNPs outside target regions compared to 65,231 SNPs inside target regions (a 129% increase). For our Illumina TrueSeq data, we obtained 222,171 high-quality SNPs outside target regions compared to 95,818 SNPs inside target regions (a 232% increase). For the data from the 1000 Genomes Project, we obtained 7,139 high-quality SNPs outside target regions compared to 1,548 SNPs inside target regions (a 461% increase).
Conclusions
These results demonstrate that a significant amount of high quality genotypes outside target regions can be obtained from exome sequencing data. These data should not be ignored in genetic epidemiology studies.
doi:10.1186/1471-2164-13-194
PMCID: PMC3416685  PMID: 22607156
Exome sequencing; SNP; Target region; Capture efficiency
10.  Vitamin supplement use during breast cancer treatment and survival: a prospective cohort study 
Background
Antioxidants may protect normal cells from the oxidative damage that occurs during radiotherapy and certain chemotherapy regimens, however, the same mechanism could protect tumor cells and potentially reduce effectiveness of cancer treatments. We evaluated the association of vitamin supplement use in the first six-months after breast cancer diagnosis and during cancer treatment with total mortality and recurrence.
Methods
We conducted a population-based prospective cohort study of 4,877 women aged 20–75 years diagnosed with invasive breast cancer in Shanghai, China between March 2002 and April 2006. Women were interviewed approximately six-months after diagnosis and followed-up by in-person interviews and record linkage with the vital statistics registry.
Results
During a mean follow-up of 4.1 years, 444 deaths and 532 recurrences occurred. Vitamin use shortly after breast cancer diagnosis was associated with reduced mortality and recurrence risk, adjusted for multiple lifestyle factors, sociodemographics, and known clinical prognostic factors. Women who used antioxidants (vitamin E, vitamin C, multivitamins) had 18% reduced mortality risk (hazard ratio (HR) = 0.82, 95% confidence interval (CI): 0.65–1.02) and 22% reduced recurrence risk (HR = 0.78, 95% CI: 0.63–0.95). The inverse association was found regardless of whether vitamin use was concurrent or non-concurrent with chemotherapy, but was only present among patients who did not receive radiotherapy.
Conclusions
Vitamin supplement use in the first six months after breast cancer diagnosis may be associated with reduced risk of mortality and recurrence.
Impact
Our results do not support the current recommendation that breast cancer patients should avoid use of vitamin supplements.
doi:10.1158/1055-9965.EPI-10-1072
PMCID: PMC3057050  PMID: 21177425
Vitamin supplements; antioxidants; breast cancer; survival; prognosis
11.  Concordance of self-reported and medical chart information on cancer diagnosis and treatment 
Background
Self-reported information is an important tool for collecting clinical information for epidemiologic studies and in clinical settings where electronic medical records are not employed and shared.
Methods
Using data collected from the Shanghai Breast Cancer Survival Study (SBCSS), a population-based, prospective cohort study of 5,042 women diagnosed with breast cancer in Shanghai, China, we compared the concordance of patient questionnaire responses to a survey administered approximately 6 months after cancer diagnosis with medical chart information obtained from the diagnostic hospitals for several disease and treatment-related variables.
Results
Of 5,042 SBCSS participants, medical chart information was available for 4,948 women (98.1%). Concordance between patient self-reported and medical chart information was high for the majority of disease-related variables, including: diagnosing hospital (agreement: 98.7%, kappa: 0.99), type of surgery conducted (94.0%, 0.53), ER/PR status (94.5%, 0.91), and tumor position (98.2%, 0.97), as well as for important calendar dates, such as date of diagnosis, surgery, and first chemotherapy treatment. The 10 most commonly used chemotherapeutic drugs were all reported with agreement rates of at least 82%, with associated kappa values that ranged from 0.41 for calcium folinate to 0.76 for vinorelbine.
Conclusions
Our study found high validity for patient self-reported information for a variety of disease and treatment-related variables, suggesting the utility of self-reports as an important source of clinical information for both epidemiological research and patient care.
doi:10.1186/1471-2288-11-72
PMCID: PMC3118949  PMID: 21592352
12.  Exercise, Tea Consumption, and Depression Among Breast Cancer Survivors 
Journal of Clinical Oncology  2010;28(6):991-998.
Purpose
To examine the association of lifestyle factors and supplement use with depression among breast cancer survivors.
Patients and Methods
In a population-based cohort study conducted between April 2002 and December 2006 in Shanghai, China, a total of 1,399 women who were diagnosed with stage 0 to III breast cancer completed 6-month and 18-month postdiagnosis, in-person interviews. Information on sociodemographic, clinical, and lifestyle factors were collected through the interviews and through review of medical charts at approximately 6 months postdiagnosis. A metabolic equivalent (MET) score was calculated from reported exercise activities. Quality of life (QOL) was evaluated by the Medical Outcomes Short Form-36 Health Survey at 6 months postdiagnosis. Depressive symptoms were measured by using a 20-item Center for Epidemiological Studies–Depression Scale at approximately 18 months postdiagnosis.
Results
Overall, 26% of women reported depressive symptoms and 13% met the criteria of clinical depression at 18 months postdiagnosis. Women with a higher exercise level (ie, ≥ 8.3 MET h/wk) were less likely to have depression than nonexercisers; the multivariate adjusted odds ratios (ORs) were 0.71 (95% CI, 0.47 to 1.07) for mild depression and 0.56 (95% CI, 0.35 to 0.88) for clinical depression in analyses controlled for sociodemographic and clinical factors and baseline QOL. Women who increased their exercise level had lower risk for depression. Regular tea consumption (ie, > 100 g dried tea leaves/mo) was inversely associated with overall depression (OR, 0.39; 95% CI, 0.19 to 0.84). No associations were found for dietary intake or supplement use with depression.
Conclusion
Regular exercise participation and tea consumption may play an important role in the prevention of depression among breast cancer survivors.
doi:10.1200/JCO.2009.23.0565
PMCID: PMC2834436  PMID: 20048185
13.  Metabolomics in Epidemiology: Sources of Variability in Metabolite Measurements and Implications 
Background
Metabolite levels within an individual vary over time. This within-individual variability, coupled with technical variability, reduces the power for epidemiological studies to detect associations with disease. Here, the authors assess the variability of a large subset of metabolites and evaluate the implications for epidemiologic studies.
Methods
Using LC-MS and GC-MS platforms, 385 metabolites were measured in 60 women at baseline and year-1 of the Shanghai Physical Activity Study, and observed patterns were confirmed in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening study.
Results
Although the authors found high technical reliability (median intra-class correlation = 0.8), reliability over time within an individual was low. Taken together, variability in the assay and variability within the individual accounted for the majority of variability for 64% of metabolites. Given this, a metabolite would need, on average, a Relative Risk of 3 (comparing upper and lower quartiles of “usual” levels) or 2 (comparing quartiles of observed levels) to be detected in 38%, 74% and 97% of studies including 500, 1000, and 5000 individuals. Age, gender, and fasting status, factors which are often of less interest in epidemiological studies were associated with 30%, 67%, and 34% of metabolites, respectively, but the associations were weak, and explained only a small proportion of the total metabolite variability.
Conclusion
Metabolomics will require large, but feasible, sample sizes to detect the moderate effect sizes typical for epidemiological studies.
Impact
We offer guidelines for determining the sample sizes needed to conduct metabolomic studies in epidemiology.
doi:10.1158/1055-9965.EPI-12-1109
PMCID: PMC3617076  PMID: 23396963
metabolomics; power; variance components; measurement error
14.  Association of Leukocyte Telomere Length With Breast Cancer Risk: Nested Case-Control Findings From the Shanghai Women's Health Study 
American Journal of Epidemiology  2013;177(7):617-624.
Telomeres are specialized chromatin structures essential for the maintenance of chromosomal integrity and stability. Telomere shortening has been linked to multiple aging-related diseases, including cancer. Evidence associating telomere length with breast cancer risk—most of which has been from retrospective case-control studies—is conflicting. We conducted a nested case-control study based on the Shanghai Women's Health Study (1997–2009) in which we evaluated the association of telomere length and breast cancer risk using peripheral blood samples collected before cancer diagnosis (601 cases and 695 controls). We used monochrome multiplex quantitative polymerase chain reaction to measure relative telomere length. Multiple logistic regressions were used to derive adjusted odds ratios with 95% confidence intervals as the measure of association. Telomere length was inversely correlated with age (r = −0.22). Women with moderately long telomeres (those in the fourth quintile) had the lowest breast cancer risk. Risk increased in a dose-response manner with decreasing quintile of telomere length; odds ratios were 1.39 (95% confidence interval (CI): 0.95, 2.04), 1.79 (95% CI: 1.17, 2.75), and 2.39 (95% CI: 1.45, 3.92), respectively, for the third, second, and first quintiles compared with the fourth quintile. A slightly elevated risk of breast cancer (odds ratio = 1.35, 95% CI: 0.90, 2.04), although one that was not statistically significant, was found in the top quintile (longest telomeres). Our results support the hypothesis that telomere shortening is associated with increased risk of breast cancer and suggest a possible elevated risk associated with long telomeres.
doi:10.1093/aje/kws291
PMCID: PMC3657533  PMID: 23444102
breast cancer; biomarkers; epidemiology; genetic factors; telomere
15.  Body Weight, Fat Distribution and Colorectal Cancer Risk: A Report from Cohort Studies of 134 255 Chinese Men and Women 
International journal of obesity (2005)  2012;10.1038/ijo.2012.152.
OBJECTIVE
To evaluate the association of body size and fat distribution with risk of colorectal cancer (CRC) in Chinese men and women.
DESIGN
Population-based, prospective cohort study.
SUBJECTS
The analysis included 134 255 Chinese adults enrolled in the Shanghai Women’s Health Study and the Shanghai Men’s Health Study, with an average follow-up of 11.0 and 5.5 years, respectively.
MEASUREMENTS
Waist circumference (WC), body mass index (BMI) and waist-to-hip ratio (WHR) were measured by trained interviewers at baseline. Multivariable Cox models were used to calculate adjusted hazard ratios (HRs) for incident CRC.
RESULTS
A total of 935 incident CRC cases were identified. Both measures of general adiposity (measured by BMI) and central adiposity (measured by WHR and WC) were significantly associated with increased risk of colon cancer in men but not in women. Multivariable adjusted HRs for colon cancer in men in the highest compared with the lowest quintiles were 2.15 (95% CI: 1.35-3.43; P for trend = 0.0006) for BMI, 1.97 (95% CI: 1.19-3.24; P for trend = 0.0004) for WHR and 2.00 (95% CI: 1.21-3.29; P for trend = 0.0002) for WC. The BMI-associated risk was attenuated in analyses stratified by WHR, while the WHR-associated risk remained significant in the high BMI stratum (HR for comparison of extreme tertiles of WHR: 3.38, 95% CI: 1.47-7.75; P for trend =0.0002). None of these anthropometric measures were significantly associated with rectal cancer.
CONCLUSION
Obesity, particularly central obesity, was associated with increased risk of colon cancer in men.
doi:10.1038/ijo.2012.152
PMCID: PMC3541452  PMID: 22986684
Obesity; colorectal cancer; cohort study
16.  Fruit and Vegetable Intake and Risk of Coronary Heart Disease: Results from Prospective Cohort Studies of Chinese Adults in Shanghai 
The British journal of nutrition  2013;111(2):353-362.
Protective associations of fruit and vegetables against coronary heart disease (CHD) have been suggested in many epidemiological studies among Western populations. However, prospective data are lacking for Asian populations. We examined the associations of fruit and vegetable intake with incidence of CHD among 67,211 women (40–70 years) and 55,474 men (40–74 years) living in Shanghai, China. Food intake was assessed using validated food-frequency questionnaires through in-person interviews. Coronary events (nonfatal myocardial infarction or fatal CHD) were identified by biennial home visits and further confirmed by medical records review. During a mean follow-up of 9.8 and 5.4 years, 148 events in women and 217 events in men were documented and verified, respectively. After adjustment for potential confounders, women in the highest quartile of total fruit and vegetable intake (median: 814 g/d) had a hazard ratio (HR) for CHD of 0.62 (95% CI 0.38, 1.02) (P for trend=0.04) compared with those in the lowest quartile (median: 274 g/d). This association was primarily driven by fruits (the HR for the highest vs. the lowest intake in women: 0.62; 95% CI, 0.37, 1.03). The strength of the association was attenuated after further controlling for history of diabetes or hypertension. For men, no significant association was found for fruit and vegetable intake when analyzed either in combination or individually. Our findings suggest that a high consumption of fruits may reduce the risk of CHD in Chinese women.
doi:10.1017/S0007114513002328
PMCID: PMC3947047  PMID: 23866068
Fruit; Vegetable; Coronary heart disease; Prospective study
17.  No Association between Ovarian Cancer Susceptibility Variants and Breast Cancer Risk among Chinese Women 
Background
As breast and ovarian cancers may have similar etiologies, this study aimed to evaluate the hypothesis that breast cancer shares common genetic susceptibility variants with ovarian cancer.
Methods
Ten genetic variants in 9 loci were previously identified to be associated with ovarian cancer risk among Caucasian women; an additional 353 variants in high linkage disequilibrium (r2≥0.6) among Han Chinese were identified. Data were available from the Affymetrix Genome Wide Array (6.0) or MACH imputation for 25 and 78 common genetic variants (minor allele frequency (MAF) ≥0.05), respectively. Associations with breast cancer risk were evaluated by additive logistic regression models among 2, 918 breast cancer cases and 2, 324 controls.
Results
No associations with breast cancer risk were evident for 103 ovarian cancer susceptibility variants in five loci. Four loci were not evaluated, as they included only rare variants (MAF<0.05).
Conclusions
Ovarian cancer susceptibility variants identified in Caucasian women were not associated with breast cancer risk among 5, 242 Chinese women.
Impact
These findings suggest that breast and ovarian cancer may not share common susceptibility variants among Chinese women.
doi:10.1158/1055-9965.EPI-12-1365
PMCID: PMC3596432  PMID: 23292081
Genetic Variants; Breast Cancer; Ovarian Cancer
18.  Genetic polymorphism of NFKB1 and NFKBIA genes and liver cancer risk: a nested case–control study in Shanghai, China 
BMJ Open  2014;4(2):e004427.
Objectives
Genetic variations of nuclear factor-κB (NF-κB) signalling pathway were found to be associated with inflammatory diseases and several malignancies. However, little is known about NF-κB pathway gene polymorphisms and susceptibility of liver cancer. The aim of this study was to investigate whether genetic variants of NFKB1 and NFKBIA were associated with risk of liver cancer in a Chinese population.
Design
The study was designed as a nested case–control study within two prospective cohorts (the Shanghai Women's Health Study, SWHS, 1996–2000 and the Shanghai Men's Health Study, SMHS, 2002–2006).
Settings
This population-based study was conducted in urban Shanghai, China.
Participants
A total of 217 incident liver cancer cases diagnosed through 31 December 2009 and 427 healthy controls matched by sex, age at baseline (±2 years) and date (±30 days) of sample collection were included in the study.
Primary and secondary outcome measures
Genetic polymorphisms of NFKB1 and NFKBIA were determined blindly by TaqMan single-nucleotide polymorphism (SNP) genotyping assay. OR and its 95% CIs were estimated by an unconditional logistic regression model to measure the association between selected SNPs and the risk of liver cancer.
Results
After adjusted for potential confounding factors, rs28362491 ins/del or del/del genotypes were associated with higher risk of liver cancer with an adjusted OR 1.54 (95% CI 1.04 to 2.28). rs230496 AG and GG genotypes were also noted with higher risk of liver cancer with an adjusted OR 1.53 (95% CI 1.03 to 2.26). Haplotype analysis indicated that carriers of the NFKB1 GA and AA (rs230525-rs230530) haplotypes had higher risk of liver cancer under an additive model. No association was observed between NFKBIA variants and risk of live cancer.
Conclusions
Our results suggest that genetic variants of NFKB1 influence liver cancer susceptibility in Chinese population, although replication in other studies is needed.
doi:10.1136/bmjopen-2013-004427
PMCID: PMC3939648  PMID: 24578542
Epidemiology
19.  Assessment of Dietary Isoflavone Intake among Middle-Aged Chinese Men1 
The Journal of nutrition  2007;137(4):1011-1016.
We evaluated the reproducibility and validity of the FFQ used in the Shanghai Men's Health Study (SMHS) for assessing dietary isoflavone intake, using multiple 24-h dietary recalls (24-HDR) and urinary isoflavones as the reference criteria, with data from the dietary validation study of the SMHS. A total of 196 study subjects completed the 24-HDR and 2 FFQ and donated a quarterly spot urine sample during the 1-y study period. Levels of urinary isoflavones were measured in a random sample of 48 study participants. The correlation coefficient between the 2 FFQ administered 1 y apart was 0.50 for soy protein intake and ranged from 0.50 to 0.51 for isoflavone intake. The correlations of isoflavone intake from the second FFQ with those from the multiple 24-HDR ranged from 0.38 (genistein) to 0.44 (glycitein), and the correlations with urinary isoflavone levels were 0.48 for total isoflavones, 0.44 for daidzein, 0.42 for genistein, and 0.54 for glycitein. The intraclass correlation coefficients for the 4 spot urine samples were 0.36, 0.42, and 0.40 for daidzein, genistein, and glycitein, respectively, and 0.62, 0.68, and 0.55 for their metabolic products equol, dihydrodaidzein, and O-desmethylangolensin, respectively. These results suggest that the SMHS FFQ can reliably and accurately measure usual intake of isoflavones, and that the levels of isoflavones in urine samples are relatively stable among men in Shanghai.
PMCID: PMC2040062  PMID: 17374669
20.  Thyroid cancer risk and dietary nitrate and nitrite intake in the Shanghai Women’s Health Study 
Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds and nitrate can disrupt thyroid homeostasis by inhibiting iodide uptake. We evaluated nitrate and nitrite intake and risk of thyroid cancer in the Shanghai Women’s Health Study that included 73,317 women, aged 40–70 years enrolled in 1996–2000. Dietary intake was assessed at baseline using a food frequency questionnaire. During approximately 11 years of follow-up, 164 incident thyroid cancer cases with complete dietary information were identified. We used Cox proportional hazards regression to estimate relatives risks (RRs). We determined the nitrate and nitrite contents of foods using values from the published literature and focusing on regional values for Chinese foods. Nitrate intake was not associated with thyroid cancer risk (RRQ4 = 0.93; 95%CI: 0.42–2.07; p for trend = 0.40). Compared with the lowest quartile, women with the highest dietary nitrite intake had about a two-fold risk of thyroid cancer (RRQ4 = 2.05; 95%CI: 1.20–3.51;) but there was not a monotonic trend with increasing intake (p for trend= 0.36). The trend with increasing nitrite intake from animal sources was significant (p for trend = 0.02) and was stronger for nitrite from processed meats (RRQ4 = 1.96; 95%CI: 1.28–2.99; p for trend <0.01). Although we did not observe an association for nitrate as hypothesized, our results suggest that women consuming higher levels of nitrite from animal sources, particularly from processed meat, may have an increased risk of thyroid cancer.
doi:10.1002/ijc.27659
PMCID: PMC3443521  PMID: 22674227
21.  IGFBP3 mRNA expression in benign and malignant breast tumors 
Breast Cancer Research  2007;9(1):R2.
Introduction
Most previous studies have focused on evaluating the association between circulating insulin-like growth factor binding protein 3 (IGFBP-3) levels and breast cancer risk. Emerging evidence over the past few years suggests that IGFBP-3 may act directly on mammary epithelial cells.
Methods
To understand the role of IGFBP-3 in breast tumorigenesis, we investigated IGFBP3 mRNA expression levels in benign and malignant breast tumors and their adjacent normal tissues using real-time quantitative PCR.
Results
Cancer tissues had significantly lower IGFBP3 expression than benign tumor tissues (p < 0.001). IGFBP3 expressions in both tumor and adjacent tissues were higher in patients who had proliferative benign tumors than in those who had non-proliferative benign tumors. Among patients with benign breast disease, IGFBP3 expression in the tumor was significantly higher than that in their adjacent normal tissue. There were no apparent associations of IGFBP3 expression in cancer tissues with either overall survival or disease-free survival in a cohort of 521 patients with breast cancer.
Conclusion
Our findings suggest that the expression level of IGFBP3 in breast tissues may be involved in breast tumorigenesis.
doi:10.1186/bcr1634
PMCID: PMC1851392  PMID: 17210081
22.  The association of meat intake and the risk of type 2 diabetes may be modified by body weight 
Aim: To investigate the association between meat intake and incidence of type 2 diabetes (type 2 DM) in a large cohort of middle-aged women.
Design, subjects and methods: Incident cases of type 2 DM were identified during an average of 4.6 years of follow-up in a prospective cohort study of 74,493 middle-aged, Chinese women (mean age ± SD =51.7± 8.97 years). Participants completed in-person interviews that collected information on type 2 DM risk factors such as dietary factors and physical activity in adulthood. Anthropometric indices were measured. Dietary intake was assessed using a validated food frequency questionnaire (FFQ). We included in the current analysis 70,609 women who had no prior history of type 2 DM at study recruitment and who had valid dietary data. The association of type 2 DM with unprocessed meat intake (g/day) and the frequency of consumption of processed meat was evaluated using the Cox model with adjustment for age, kcals/day, body mass index (BMI), waist to hip ratio (WHR), vegetable intake, smoking, alcohol consumption, physical activity, income level, education level, occupation status, and history of hypertension and chronic disease at baseline.
Principal results: We identified 1972 incident cases of type 2 DM during a total of 326,581 person-years of follow up. Intake of unprocessed meat, particularly poultry, was associated with a decrease in the risk of type 2 DM in this cohort. The fully adjusted relative risks (RRs) for quintiles of total unprocessed meat intake were 1.00, 0.78, 0.83, 0.74, and 0.83 (P for trend: <0.01). When the joint effect between meat intake and BMI categories was evaluated, high intake of total unprocessed meat appeared to be associated with an increased risk of type 2 DM among obese women but a reduced risk among lean women (P value for the interaction tests = 0.05). Processed meat consumption was positively associated with the risk of type 2 DM. The adjusted RR was 1.15 (95% 1.01-1.32) in women consuming processed meats compared to those who did not consume processed meats (P=0.04).
Conclusions: Processed meat intake was positively associated with the risk of type 2 DM. There was an indication that the effect of unprocessed meat intake on type 2 DM may be modified by BMI.
PMCID: PMC1633824  PMID: 17088942
type 2 diabetes; meat intake; middle-aged women
23.  Genetic polymorphisms in the matrix metalloproteinase 12 gene (MMP12) and breast cancer risk and survival: the Shanghai Breast Cancer Study 
Breast Cancer Research  2005;7(4):R506-R512.
Introduction
Matrix metalloproteinase 12 (MMP12) is a proteolytic enzyme responsible for cleavage of plasminogen to angiotensin, which has an angiostatic effect. Using data from a population-based case–control study conducted among Chinese women in Shanghai, we evaluated the association of breast cancer risk and survival with two common polymorphisms in the MMP12 gene: A-82G in the promoter region and A1082G in exon, resulting in an amino acid change of asparagine to serine.
Methods
Included in the study were 1,129 cases and 1,229 age-frequency-matched population controls. Breast cancer patients were followed up to determine the intervals of overall survival and disease-free survival.
Results
The frequencies of the G allele in the A-82G and A1082G polymorphism among controls were 0.029 and 0.107, respectively. There were no associations between MMP12 polymorphisms and breast cancer risk. Patients with the AG or GG genotype of the A1082G polymorphism showed poorer overall survival (though the difference was not statistically significant) than patients with the AA genotype (hazard ratio 1.36, 95% CI 0.92 to 2.00).
Conclusion
This result suggests that MMP12 A1082G polymorphism may be related to prognosis in breast cancer patients. Additional studies with larger sample sizes are warranted.
doi:10.1186/bcr1033
PMCID: PMC1175062  PMID: 15987457
24.  Leveraging Epidemiology and Clinical Studies of Cancer Outcomes: Recommendations and Opportunities for Translational Research 
As the number of cancer survivors continues to grow, research investigating the factors that affect cancer outcomes, such as disease recurrence, risk of second malignant neoplasms, and the late effects of cancer treatments, becomes ever more important. Numerous epidemiologic studies have investigated factors that affect cancer risk, but far fewer have addressed the extent to which demographic, lifestyle, genomic, clinical, and psychosocial factors influence cancer outcomes. To identify research priorities as well as resources and infrastructure needed to advance the field of cancer outcomes and survivorship research, the National Cancer Institute sponsored a workshop titled “Utilizing Data from Cancer Survivor Cohorts: Understanding the Current State of Knowledge and Developing Future Research Priorities” on November 3, 2011, in Washington, DC. This commentary highlights recent findings presented at the workshop, opportunities to leverage existing data, and recommendations for future research, data, and infrastructure needed to address high priority clinical and research questions. Multidisciplinary teams that include epidemiologists, clinicians, biostatisticians, and bioinformaticists will be essential to facilitate future cancer outcome studies focused on improving clinical care of cancer patients, identifying those at high risk of poor outcomes, and implementing effective interventions to ultimately improve the quality and duration of survival.
doi:10.1093/jnci/djs473
PMCID: PMC3545903  PMID: 23197494
25.  Gene-Environment Interactions for Breast Cancer Risk Among Chinese Women: A Report From the Shanghai Breast Cancer Genetics Study 
American Journal of Epidemiology  2012;177(2):161-170.
Genome-wide association studies have identified approximately 20 susceptibility loci for breast cancer. A cumulative genetic risk score (GRS) was constructed from 10 variants with replicated associations among participants of the Shanghai Breast Cancer Genetics Study (Shanghai, China, 1996–1998 and 2002–2005). Interactions between the GRS and 11 breast cancer risk factors were evaluated. Among the 6,408 study participants, no evidence of effect modification was found with the GRS for age at menarche, age at menopause, age at first live birth/parity, total months of breastfeeding, family history of breast cancer, history of benign breast disease, hormone replacement therapy, body mass index, waist/hip ratio, or regular physical activity. The effect of the GRS was least homogeneous by duration of menstruation; further analysis indicated a nominally significant interaction with one genetic variant. The mitochondrial ribosomal protein S30 gene (MRPS30) rs10941679 was associated with breast cancer risk only among women with more than 30 years of menstruation (odds ratio = 1.15, 95% confidence interval: 1.05, 1.26). Although this multiplicative interaction reached a nominal significance level (P = 0.037), it did not withstand correction for multiple comparisons. In conclusion, this study revealed no apparent interactions between genome-wide association study-identified genetic variants and breast cancer risk factors in the etiology of this common cancer.
Abbreviations: CI, confidence interval; GRS, genetic risk score; OR, odds ratio; SNP, single nucleotide polymorphism.
doi:10.1093/aje/kws238
PMCID: PMC3590035  PMID: 23221726
breast cancer risk; effect measure modification; gene-environment interaction; genetic variants; genome-wide association study

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