Correspondence to: Xiao-Ou Shu, MD, PhD, Vanderbilt Epidemiology Center, 2525 West End Ave, Ste 600 (IMPH), Nashville, TN 37203-1738 (e-mail: firstname.lastname@example.org) 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: email@example.com).Background
Epidemiologic studies on the relationship between vitamin intake and liver cancer risk are sparse and inconsistent.
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.
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.
Vitamin E intake, either from diet or supplements, may reduce the risk of liver cancer.
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.
body mass index; endometrial neoplasms; genetics; genome-wide association study; obesity; risk factors
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.
breast neoplasms; China; hormones; receptors, estrogen; receptors, progesterone; risk factors; women
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.
body mass index; genome-wide association study; linkage disequilibrium; obesity; polymorphism, genetic; women
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.
fruits; vegetables; carotenoids; dietary intake; lung cancer; epidemiological
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.
breast neoplasms; cohort studies; exercise; quality of life
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.
Body mass index; central obesity; weight change; breast cancer; survival
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).
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).
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.
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.
1-hydroxypyrene glucuronide; Polycyclic aromatic hydrocarbons; Colorectal cancer; China
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.
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).
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.
Exome sequencing; SNP; Target region; Capture efficiency
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.
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.
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.
Vitamin supplement use in the first six months after breast cancer diagnosis may be associated with reduced risk of mortality and recurrence.
Our results do not support the current recommendation that breast cancer patients should avoid use of vitamin supplements.
Vitamin supplements; antioxidants; breast cancer; survival; prognosis
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.
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.
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.
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.
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.
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.
Regular exercise participation and tea consumption may play an important role in the prevention of depression among breast cancer survivors.
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.
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.
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.
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.
Our findings suggest that the expression level of IGFBP3 in breast tissues may be involved in breast tumorigenesis.
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.
type 2 diabetes; meat intake; middle-aged women
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.
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.
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).
This result suggests that MMP12 A1082G polymorphism may be related to prognosis in breast cancer patients. Additional studies with larger sample sizes are warranted.
Background Whether soy food consumption may protect against coronary heart disease (CHD) remains controversial. No previous study has used biomarkers of soy intake in assessing the relationship between soy consumption and CHD. Biomarkers that reflect both intake and metabolism may be more informative than self-reports of dietary intake.
Methods We examined associations of urinary isoflavonoids, a biomarker of soy or soy isoflavone intake, with risk of CHD in a case–control study nested within two prospective cohort studies of Chinese adults in Shanghai. Cases were defined as subjects with no history of CHD at baseline who developed incident CHD during follow-up. Control subjects were randomly selected from those who remained free of CHD and matched to cases by sex, age, date and time of sample collection and antibiotic use. Baseline urinary isoflavonoids (daidzein, genistein, glycitein, equol, O-desmethylangolensin, dihydrodaidzein and dihydrogenistein) were compared between cases (n = 377) and control subjects (n = 753). Conditional logistic regression was used to evaluate the associations.
Results Total urinary isoflavonoids were not associated with CHD in either women or men. However, urinary equol excretion showed a significant inverse association with CHD in women. The adjusted odds ratios (95% confidence intervals) for CHD across increasing quartiles of equol levels in women were 1 (reference), 0.61 (0.32, 1.15), 0.51 (0.26, 0.98) and 0.46 (0.24, 0.89) (P = 0.02 for trend).
Conclusions Our study suggests for the first time that equol, a bioactive metabolite of soy isoflavone daidzein, may be inversely associated with risk of CHD in women.
coronary disease; isoflavones; soy foods
Telomeres are specialized chromatin structures essential for maintenance of chromosomal integrity and stability. Abnormal alteration of telomere length has been linked to several cancers; however, epidemiologic evidence regarding the association of telomere length with colorectal cancer risk has been conflicting.
We conducted a nested case-control study to evaluate the association between telomere length and colorectal cancer risk using peripheral blood samples collected prior to cancer diagnosis. The study included 441 women with incident colorectal cancer and 549 matched controls. Monochrome multiplex quantitative PCR was applied to measure relative telomere length. Multiple logistic regressions were used to derive adjusted odds ratios (OR) with 95% confidence intervals (CI) as the measure of association between telomere length and subsequent colorectal cancer risk.
A U-shaped association was observed between telomere length and colorectal cancer risk (test for nonlinearity P = 0.0112). Women with telomere length in the third quintile (40th to 60th percentiles) had the lowest risk of colorectal cancer, and the risks were elevated with a shorter or longer telomere length. This U-shaped association did not statistically differ for colon cancer and rectum cancer.
Conclusions and Impact
Our prospective study revealed a U-shaped association between telomere length in peripheral blood cells and colorectal cancer risk. Our findings provide strong evidence that both very short and very long telomeres are associated with increased risk of colorectal cancer.
Abnormal sleep duration, either long or short, is associated with disease risk and mortality. Little information is available on sleep duration and its correlates among Chinese women.
Using information collected from 68,832 women who participated in the Shanghai Women’s Health Study (SWHS), we evaluated sleep duration and its correlations with sociodemographic and lifestyle factors, health status, and anthropometric measurements and their indexes using polynomial logistic regression.
The mean age of the study population was 59.6 years (SD=9.0; range: 44.6–79.9 years) at time of sleep duration assessment. Approximately 80% of women reported sleeping 6–8 hours per day, 11.5% slept five hours or less, and 8.7% slept nine hours or more. As expected, age was the strongest predictor for sleep duration and was negatively correlated with sleep duration. In general, sleep duration was positively associated with energy intake, intakes of total meat and fruits, body mass index (BMI), waist-hip ratio (WHR), and waist circumference (WC) after adjustment for age and other factors. Both short and long sleep duration were negatively associated with education level, family income, and leisure-time physical activity and positively associated with number of live births, history of night shift work, and certain chronic diseases, compared to sleep duration around seven hours/day (6.5–7.4 hours/day). Short sleep duration was related to tea consumption and passive smoking. Long sleep duration was related to menopausal status and marital status.
In this large, population-based study, we found that sleep duration among middle-aged and elderly Chinese women was associated with several sociodemographic and lifestyle factors and with disease status. The main limitation of the study is the cross-sectional design that does not allow us to draw any causal inference. However, this study provides information for future investigation into the nature of these associations so that recommendations can be developed to reduce sleep problems in middle-aged and elderly Chinese women. It also provides important information on potential confounders for investigation of sleep duration on health outcomes in this population.
Sleep duration; socio-economic factor; lifestyle; health status; BMI; correlation; Chinese
We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC cases, 2,115 ESCC cases, and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex, and study, multiple variants at 10q23 had genome-wide significance for GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×1010; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10−9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10−15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.
Menopausal symptoms have been suggested to be an indicator of better prognosis among patients treated for breast cancer, because women who experience these symptoms usually have a lower level of estrogen. We tested this hypothesis in a population-based, prospective cohort study involving 4,842 women with stage 0 to III primary breast cancer who were enrolled in the Shanghai Breast Cancer Survival Study between March 2002 and April 2006, were aged 20 to 75 years, and were recruited 6 months post-diagnosis. They were followed-up by in-person surveys and record linkages with the vital statistics registry. Cox regression analysis was used to evaluate the association of menopausal symptoms at baseline with breast cancer recurrence. Approximately 56% of patients experienced at least one menopausal symptom, including hot flashes, night sweats, and/or vaginal dryness at baseline. During a median follow-up period of 5.3 years, 720 women had a recurrence. Experiencing hot flashes or having ≥2 menopausal symptoms was associated with lower risk of recurrence among premenopausal women (hazard ratio [HR]=0.77, 95% confidence interval [CI]: 0.62-0.96 for hot flashes; 0.73, 0.56-0.96 for ≥2 menopausal symptoms). Lower recurrence risk in relation to hot flashes was also observed among women who were not overweight/obese (HR=0.78, 95% CI: 0.64-0.99), those with relatively low waist-to-hip ratio (WHR) (HR=0.77, 95% CI: 0.61-0.97), and those who used tamoxifen (HR=0.75, 95% CI: 0.58-0.98). Consistently experiencing multiple menopausal symptoms was associated with lower recurrence risk among women with low WHR or who used tamoxifen. This large, population-based cohort study of women with breast cancer confirms that experiencing menopausal symptoms is an indicator of favorable breast cancer prognosis.
Vitamin D deficiency has been consistently associated with obesity. However, it is unclear whether vitamin D deficiency is the cause or consequence of obesity. We investigated this question by evaluating the association between genetic variants in vitamin D metabolism pathway genes and obesity-related traits. Using directly genotyped and imputed data from a genome-wide association (GWA) study of 6,922 women aged 25–70 years, we examined the association of 198 SNPs in vitamin D pathway genes (CYP27A1, CYP27B1, CYP24A1, CYP2R1, GC, and VDR) with body mass index (BMI) and body weight. Per allele beta (β) estimates were calculated for this association using linear regression models, controlling for age, square of age, menopausal status, and sample sets. Overall, only two SNPs (rs2248359 in CYP24A1 and rs10832313 in CYP2R1) had a nominally significant association with BMI and weight (P=0.02 for both) with no variation observed by menopausal status, physical activity, or dietary energy intake. None of the SNPs examined in the VDR gene were associated with BMI or weight. Our findings suggest that common genetic variations in vitamin D pathway genes do not play a major role in obesity among Chinese women.
genetic variants; body mass index; body weight; obesity; vitamin D pathway; genome-wide association study; women; China
Previous studies suggest that melatonin may act on cancer growth through a variety of mechanisms, most notably by direct anti-proliferative effects on breast cancer cells and via interactions with the estrogen pathway. Three genes are largely responsible for mediating the downstream effects of melatonin: melatonin receptors 1a and 1b (MTNR1a and MTNR1b), and Arylalkylamine N-acetyltransferase (AANAT). It is hypothesized that genetic variation in these genes may lead to altered protein production or function. To address this question, we conducted a comprehensive evaluation of the association between common single nucleotide polymorphisms (SNPs) in the MTNR1a, MTNR1b, and AANAT genes and breast cancer risk among 2,073 cases and 2,083 controls, using a two-staged analysis of genome-wide association (GWAS) data among women of the Shanghai Breast Cancer Study. Results demonstrate two SNPS were consistently associated with breast cancer risk across both study stages. Compared with MTNR1b rs10765576 major allele carriers (GG or GA), a decreased risk of breast cancer was associated with the AA genotype (OR=0.78, 95% CI=0.62–0.97, p=0.0281). Although no overall association was seen in the combined analysis, the effect of MTNR1a rs7665392 was found to vary by menopausal status (p-value for interaction=0.001). Premenopausal women with the GG genotype were at increased risk for breast cancer as compared to major allele carriers (TT or TG) (OR=1.57, 95% CI=1.07–2.31, p=0.020), while post-menopausal women were at decreased risk (OR=0.58, 95% 0.36–0.95, p=0.030). No significant breast cancer associations were found for variants in AANAT. These results suggest that common genetic variation in the MTNR1a and 1b genes may contribute to breast cancer susceptibility, and that associations may vary by menopausal status. Given that multiple variants in high linkage disequibrium with MTNR1b rs76653292 have been associated with altered function or expression of insulin and glucose family members, further research may focus on clarifying this relationship.
Melatonin; gene; polymorphism; breast cancer; risk
Previous studies of the association of meat intake and meat-derived mutagen exposure with breast cancer risk have produced inconsistent results. We evaluated this association in a population-based case-control study of incident breast cancer conducted in Nashville, United States, including 2,386 breast cancer cases and 1,703 healthy women controls. Telephone interviews were conducted to obtain information related to meat intake including amount, cooking methods, and doneness levels, as well as other known or hypothesized risk factors for breast cancer. Unconditional logistic regression was used to derive odds ratios (ORs) after adjusting for potential confounders. High intake of red meat was associated with a significantly elevated risk of breast cancer (P-trend <0.001). The association was particularly strong for high intake of well-done red meat (P-trend <0.001), with an adjusted OR of 1.5 (95% CI = 1.3–1.9) for the highest versus the lowest quartile. Associations between red meat and breast cancer risk were slightly stronger for postmenopausal women than for premenopausal women. Meat-derived mutagens such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, were significantly associated with increased breast cancer risk among postmenopausal women only (P-trend = 0.002 and 0.003, respectively). The results from this study provide strong support for the hypotheses that high red meat intake and meat-derived mutagen exposure may be associated with an increase in breast cancer risk.
Dietary factors; nutrition epidemiology; meat-derived mutagens; heterocyclic amines breast cancer
Few data are available regarding depression among Asian breast cancer survivors.
We estimated the prevalence of depression and its correlates among 1400 participants of a population-based cohort study of women with stage 0–IV breast cancer in Shanghai, China. Through in-person interviews conducted at 6 months and 18 months post-diagnosis and review of medical charts, information on sociodemographic and clinical factors and quality of life (QOL) were collected. Depression was measured by the 20-item Center for Epidemiologic Studies Depression Scale 18 months after diagnosis.
Approximately 26% of participants had mild to severe depression and 13% fulfilled the criteria of clinical depression at 18 months post-diagnosis. Women with lower income were more likely to have depression than those with higher income (prevalence: 16.6% vs. 6.9% for mild depression and 17.1% vs. 5.5% for clinical depression, respectively). Depression was more common among women who were widowed (18.9%) or divorced/separated/single (16.4%) than those who were married (11.8%). Women with comorbidity were more likely to have clinical depression (17.3% vs 11.2%). Multivariate analysis showed that low income, marital status, comorbidity, and low QOL scores were independent predictors for depression. We did not find that prevalence of depression differed by menopausal status, estrogen or progesterone receptor status, disease stage, or cancer-related treatments.
Depression is common among Asian women with breast cancer. Routine screening and prevention of depression are warranted among women with breast cancer.
depression; breast cancer; prevalence; risk factor