Improved risk scoring systems for colorectal cancer screening in Shanghai, China.

BACKGROUND: An optimal risk-scoring system enables more targeted offers for colonoscopy in colorectal cancer (CRC) screening. This analysis aims to develop and validate scoring systems using parametric and non-parametric methods for average-risk populations. METHODS: Screening data of 807,695 subjects and 2806 detected cases in the first-round CRC screening program in Shanghai were used to develop risk-predictive models and scoring systems using logistic-regression (LR) and artificial-neural-network (ANN) methods. Performance of established scoring systems was evaluated using area under the receiver operating characteristic curve (AUC), calibration, sensitivity, specificity, number of high-risk individuals and potential detection rates of CRC. RESULTS: Age, sex, CRC in first-degree relatives, chronic diarrhoea, mucus or bloody stool, history of any cancer and faecal-immunochemical-test (FIT) results were identified as predictors for the presence of CRC. The AUC of LR-based system was 0.642 when using risk factors only in derivation set, and increased to 0.774 by further incorporating one-sample FIT results, and to 0.808 by including two-sample FIT results, while those for ANN-based systems were 0.639, 0.763 and 0.805, respectively. Better calibrations were observed for the LR-based systems than the ANN-based ones. Compared with the currently used initial tests, parallel use of FIT with LR-based systems resulted in improved specificities, less demands for colonoscopy and higher detection rates of CRC, while parallel use of FIT with ANN-based systems had higher sensitivities; incorporating FIT in the scoring systems further increased specificities, decreased colonoscopy demands and improved detection rates of CRC. CONCLUSIONS: Our results indicate the potentials of LR-based scoring systems incorporating one- or two-sample FIT results for CRC mass screening. External validation is warranted for scaling-up implementation in the Chinese population.

UACA locus is associated with breast cancer chemoresistance and survival.

Few germline genetic variants have been robustly linked with breast cancer outcomes. We conducted trans-ethnic meta genome-wide association study (GWAS) of overall survival (OS) in 3973 breast cancer patients from the Pathways Study, one of the largest prospective breast cancer survivor cohorts. A locus spanning the UACA gene, a key regulator of tumor suppressor Par-4, was associated with OS in patients taking Par-4 dependent chemotherapies, including anthracyclines and anti-HER2 therapy, at a genome-wide significance level ([Formula: see text]). This association was confirmed in meta-analysis across four independent prospective breast cancer cohorts (combined hazard ratio = 1.84, [Formula: see text]). Transcriptome-wide association study revealed higher UACA gene expression was significantly associated with worse OS ([Formula: see text]). Our study identified the UACA locus as a genetic predictor of patient outcome following treatment with anthracyclines and/or anti-HER2 therapy, which may have clinical utility in formulating appropriate treatment strategies for breast cancer patients based on their genetic makeup.

MicroRNA-374b inhibits breast cancer progression through regulating CCND1 and TGFA genes.

Emerging evidence indicates that microRNAs (miRNAs) play a critical role in breast cancer development. We recently reported that a higher expression of miR-374b in tumor tissues was associated with a better disease-free survival of triple-negative breast cancer (TNBC). However, the functional significance and molecular mechanisms underlying the role of miR-374b in breast cancer are largely unknown. In this current study, we evaluated the biological functions and potential mechanisms of miR-374b in both TNBC and non-TNBC. We found that miR-374b was significantly downregulated in breast cancer tissues, compared to adjacent tissues. MiR-374b levels were also lower in breast cancer cell lines, as compared to breast epithelial cells. In vitro and in vivo studies demonstrated that miR-374b modulates the malignant behavior of breast cancer cells, such as cell proliferation in 2D and 3D, cell invasion ability, colony-forming ability and tumor growth in mice. By using bioinformatics tools, we predicted that miR-374b plays a role in breast cancer cells through negatively regulating cyclin D1 (CCND1) and transforming growth factor alpha (TGFA). We further confirmed that CCND1 and TGFA contribute to the malignant behavior of breast cancer cells in vitro and in vivo. Our rescue experiments showed that overexpressing CCND1 or TGFA reverses the phenotypes caused by miR-374b overexpression. Taken together, our studies suggest that miR-374b modulates malignant behavior of breast cancer cells by negatively regulating CCND1 and TGFA genes. The newly identified miR-374b-mediated CCND1 and TGFA gene silencing may facilitate a better understanding of the molecular mechanisms of breast cancer progression.

Soy Food Consumption, Exercise, and Body Mass Index and Osteoporotic Fracture Risk Among Breast Cancer Survivors: The Shanghai Breast Cancer Survival Study.

BACKGROUND: Breast cancer survivors have a high incidence of osteoporosis-related fractures; the associated factors are understudied. We investigated incidence of bone fracture and its associations with soy food consumption, exercise, and body mass index among breast cancer survivors. METHODS: This prospective study included 4139 stage 0-III breast cancer patients and 1987 pre-/perimenopausal and 2152 postmenopausal patients. Fractures were assessed at 18 months and at 3, 5, and 10 years after cancer diagnosis. Osteoporotic fractures were defined as fractures caused by falls from standing height and at sites associated with osteoporosis. Exercise and soy isoflavone intake were assessed at 6 and 18 months postdiagnosis. Weight and height were measured at baseline. Lifetable and Cox regression analyses were employed. All statistical tests were two sided. RESULTS: The 10-year incidence for osteoporotic fractures was 2.9% and 4.4% for pre-/perimenopausal and postmenopausal patients, respectively. High soy isoflavone intake was associated with reduced risk among pre-/perimenopausal patients (hazard ratio [HR] = 0.22, 95% confidence interval [CI] = 0.09 to 0.53, for soy isoflavone mg/d ≥56.06 vs <31.31; P trend < .001) but not among postmenopausal patients (P interaction < .01). Overweight (vs normal weight) was a risk factor for pre-/perimenopausal patients (HR = 1.81, 95% CI = 1.04 to 3.14) but not for postmenopausal patients (HR = 0.67, 95% CI = 0.43 to 1.03; P interaction = .01). Exercise was inversely associated with osteoporotic fractures in postmenopausal patients (HR = 0.56, 95% CI = 0.33 to 0.97, for metabolic equivalents hours ≥12.6 vs <4.5) following a dose-response pattern (P trend = .035), an association not modified by menopausal status. CONCLUSIONS: Our findings, especially the novel association of soy food intake with osteoporotic fractures in breast cancer survivors, if confirmed, can help guide future strategies for fracture risk reduction in this vulnerable population.

Gene expression in triple-negative breast cancer in relation to survival.

PURPOSE: The identification of biomarkers related to the prognosis of triple-negative breast cancer (TNBC) is critically important for improved understanding of the biology that drives TNBC progression. METHODS: We evaluated gene expression in total RNA isolated from formalin-fixed paraffin-embedded tumor samples using the NanoString nCounter assay for 469 TNBC cases from the Shanghai Breast Cancer Survival Study. We used Cox regression to quantify Hazard Ratios (HR) and corresponding confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS) in models that included adjustment for breast cancer intrinsic subtype. Of 302 genes in our discovery analysis, 22 were further evaluated in relation to OS among 134 TNBC cases from the Nashville Breast Health Study and the Southern Community Cohort Study; 16 genes were further evaluated in relation to DFS in 335 TNBC cases from four gene expression omnibus datasets. Fixed-effect meta-analysis was used to combine results across data sources. RESULTS: Twofold higher expression of EOMES (HR 0.90, 95% CI 0.83-0.97), RASGRP1 (HR 0.89, 95% CI 0.82-0.97), and SOD2 (HR 0.80, 95% CI 0.66-0.96) was associated with better OS. Twofold higher expression of EOMES (HR 0.89, 95% CI 0.81-0.97) and RASGRP1 (HR 0.87, 95% CI 0.81-0.95) was also associated with better DFS. On the contrary, a doubling of FA2H (HR 1.14, 95% CI 1.06-1.22) and GSPT1 (HR 1.33, 95% CI 1.14-1.55) expression was associated with shorter DFS. CONCLUSIONS: We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.

Cancer incidence in urban Shanghai, 1973-2010: an updated trend and age-period-cohort effects.

BACKGROUND: To provide a comprehensive overview of temporal trends in cancer incidence during 1973-2010 in urban Shanghai. METHODS: The estimated annual percent changes (EAPCs) for the whole period and for the time segments in age-standardized incidence rates (ASR) were evaluated with Joinpoint analysis. Age-period-cohort (APC) models were modeled to examine the effects of age, period and birth cohort on cancer incidence. RESULTS: The overall ASR decreased slightly and significantly in males (EAPC of -0.41) but increased significantly in females (EAPC of 0.57) during 1973-2010 in urban Shanghai. The incidence trend was not linear and varied by time segments. During the most recent 10 years (2001-2010), the ASR in males decreased by 1.65% per year and stabilized in females. Incidence rates continued to decline during 1973-2010 for esophagus, stomach, and liver cancer in both sexes, as well as male lung cancer and cervix cancer. It should be noted that it was the first time to document a significant decline in lung cancer incidence among males during 1973-2010 with EAPC of -0.58%, and a notable upward for cervix cancer since 1996 with EAPC of 8.94%. Unfavorable trends in incidence were observed for the most common cancer sites in the 38 years period: colorectum, gallbladder & biliary tract, pancreas, kidney, bladder, brain & central nervous system (CNS), thyroid, non-Hodgkin's lymphoma (NHL), prostate, female breast, corpus uteri, and ovary. APC analysis showed age, period and birth cohort yielded different effects by cancer sites. CONCLUSIONS: The observed trends primarily reflect dramatic changes in socioeconomic development and lifestyles in urban Shanghai over the past four decades.

Body mass index and weight change in relation to triple-negative breast cancer survival.

The aim of this study was to evaluate the influence of body mass index (BMI), weight change on triple-negative breast cancer (TNBC) prognosis in a population-based prospective cohort study. The current analysis included 518 participants diagnosed with TNBC in Shanghai Breast Cancer Survival Study. Weight at 1 year prior to cancer diagnosis, at diagnosis, and at 6, 18 and 36 months after cancer diagnosis and height at 6 months after cancer diagnosis were assessed. Disease-free survival (DFS) and overall survival (OS) were evaluated in relation to BMI and weight change using Cox proportional hazard models. Obesity (BMI ≥ 28.0 kg/m(2)) at 1-year pre-diagnosis was associated with higher risk of total mortality and recurrence/disease-specific mortality, with multivariate hazard ratios (HRs) of 1.79 (95 % CI 1.06-3.03) and 1.83 (95 % CI 1.05-3.21), respectively. The associations between BMI and TNBC prognosis attenuated over time from pre-diagnosis to post-diagnosis. Compared with stable weight (change within 5 %), weight loss ≥5 % at 18- or 36-month post-diagnosis was related with higher risk of total mortality and recurrence/disease-specific mortality. Respective multivariate HRs were 2.08 (95 % CI 1.25-3.46) and 1.42 (95 % CI 0.77-2.63) for OS, and 2.50 (95 % CI 1.45-4.30) and 2.17 (95 % CI 1.14-4.12) for DFS. However, the association of weight loss and OS/DFS attenuated after excluding patients whose weight was measured after recurrence. Weight gain ≥5 % at 18- or 36-month post-diagnosis was associated with a non-significant increased risk of death. The results showed that obesity pre-diagnosis and weight loss post-diagnosis was inversely associated with TNBC prognosis. Emphasis on maintaining stable weight after cancer diagnosis for TNBC patients may be considered.

ALDH1A1 mRNA expression in association with prognosis of triple-negative breast cancer.

ALDH1 is a crucial element in the retinoic acid signaling pathway regulating the self-renewal and differentiation of normal stem cells, and may play an important role in cancer progression. However, research on ALDH1 gene expression and breast cancer prognosis has yielded conflicting results. We evaluated the association between tumor tissue ALDH1A1/ALDH1A3 mRNA expression and triple-negative breast cancer (TNBC) prognosis in the Shanghai Breast Cancer Survival Study (SBCSS, N=463), Nashville Breast Health Study (NBHS, N=86), and Southern Community Cohort Study (SCCS, N=47). Gene expression was measured in RNA isolated from breast cancer tissues. In the SBCSS, higher ALDH1A1 mRNA level was associated with improved disease-free (HR=0.87, 95% CI: 0.80-0.95, per log unit change) and overall survival (HR=0.85, 95% CI: 0.78-0.93 per log unit change) independent of age at diagnosis, TNM stage and treatment. We replicated the findings for overall survival in the NBHS and SCCS (HR = 0.27, 95% CI: 0.10-0.73) and for disease-free survival by a meta-analysis of four publicly-available gene expression datasets (HR = 0.86, 95% CI: 0.76-0.97). No significant association was found for ALDH1A3.Our study suggests high expression of ALDH1A1 mRNA in tumor tissues may be an independent predictor of a favorable TNBC outcome.

Modifiable Lifestyle Factors and Triple-negative Breast Cancer Survival: A Population-based Prospective Study.

BACKGROUND: Very little is known about the effect of modifiable lifestyle factors on outcomes of triple-negative breast cancer. We examined this association in a population-based prospective cohort study of patients with triple-negative breast cancer. METHODS: A total of 518 women with confirmed triple-negative breast cancer, recruited by the Shanghai Breast Cancer Survival Study, completed 6-, 18-, 36-, and 60-month postdiagnosis surveys. We applied Cox proportional hazard models to evaluate the associations. RESULTS: The mean age at diagnosis was 53.4 (standard deviation = 10.6) years old. After a median follow-up of 9.1 years (range: 0.6-11.8), 128 deaths and 112 recurrences were documented. Exercise during the first 60 months postdiagnosis was inversely associated with total mortality and recurrence/disease-specific mortality with adjusted hazard ratios (HRs) of 0.67 (95% confidence interval [CI] = 0.46, 0.96) and 0.58 (95% CI = 0.39, 0.86), respectively. Women with higher exercise-metabolic equivalent scores (≥7.6 metabolic equivalent-hours/week) and longer duration of exercise (≥2.5 hours/week) had lower risk of total and recurrence/disease-specific mortality than did nonexercisers. Compared with nontea drinkers, survival was better among women who were regular tea drinkers during the first 60 months for all cause (HR = 0.57, 95% CI = 0.34, 0.93) and recurrence/disease-specific mortality (HR = 0.54, 95% CI = 0.31, 0.96). There was no dose-response pattern for tea consumption. No interactions were observed for body mass index, menopausal status, and comorbidity. CONCLUSIONS: These findings show that postdiagnosis exercise and tea intake were associated with improved survival among women with triple-negative breast cancer.

Tumor tissue microRNA expression in association with triple-negative breast cancer outcomes.

We evaluated suggested metastasis-related microRNAs (miRNAs) for their associations with disease-free survival (DFS) and overall survival (OS) of triple-negative breast cancer (TNBC). In a cohort of 456 TNBC cases, we systematically evaluated 57 previously reported metastasis-related miRNAs in tumor tissue using the NanoString nCounter assay. Cox regression was applied to evaluate miRNA expression in association with DFS and OS. In vitro assays using the TNBC cell line MDA-MB-231 were also conducted to validate epidemiological study findings. During a median follow-up of 5.3 years, 112 deaths and 97 recurrences were documented. High levels of miR-374b-5p, miR-218-5p, or miR-126-3p, or low levels of miR-27b-3p were independently associated with a favorable TNBC outcome (P < 0.01 for all). A composite score based on the levels of these four miRNAs was associated with DFS, with hazard ratios (95 % confidence interval) of 0.70 (0.43-1.15), 0.51 (0.29-0.90), and 0.18 (0.09-0.37) for the second, third, and fourth compared to the lowest quartile. Incorporating the miRNA score with known TNBC outcome predictors, i.e., age at diagnosis, tumor stage, and basal-like subtype, increased the C-index for predicting DFS from 0.68 to 0.74. Additionally, miR-126-3p was correlated with basal-like breast cancer, and miR-374b-5p modified the therapeutic effects of 5-Fluorouracil and Cyclophosphamide treatments in basal-like breast cancer patients. Restoring miR-126-3p, miR-218-5p, or miR-374b-5p, or inhibiting miR-27b-3p in MDA-MB-231 cells reduced cell proliferation. miR-374b-5p suppressed cell invasion and miR-218-5p inhibited colonization. This study provides strong evidence that the expression levels of miR-374b-5p, miR-27b-3p, miR-126-3p, and miR-218-5p in tumor tissues predict TNBC outcomes.

Soy isoflavone intake and bone mineral density in breast cancer survivors.

PURPOSE: Low bone mineral density (BMD) is common among breast cancer survivors due to acute estrogen deprivation. Soy food is a rich source of phytoestrogens, namely isoflavones, known to have both estrogenic and anti-estrogenic effects. The objective of the study was to assess the association between soy consumption and BMD in breast cancer survivors, which has not previously been evaluated. METHODS: Forearm BMD was evaluated using dual-energy X-ray absorptiometry at 60 months post-diagnosis for 1,587 participants of the Shanghai Breast Cancer Survival Study. Soy intakes collected at 6, 18, and 36 months post-diagnosis were averaged, and the association with BMD, osteopenia, and osteoporosis was evaluated using linear and logistic regression. RESULTS: The mean (standard deviation) intake of isoflavones was 48.1 (28.0) mg/day. Soy intake was inversely associated with BMD and positively associated with osteoporosis. Compared with the lowest quartile, the highest quartile of soy isoflavone intake, ≥ 62.64 mg/day, was associated with a reduction of BMD by 1.95% [95% confidence interval (CI) -3.54, -0.36%] and an increased odds ratio of 1.69 for osteoporosis (95% CI 1.09, 2.61). The inverse association was predominantly seen among women who recently entered menopause (≤ 5 years). CONCLUSION: In contrast to observations from general populations, high soy intake (≥ 62.64 mg of soy isoflavone/day) was associated with lower proximal forearm BMD among breast cancer survivors, particularly during the early years of menopause. Our finding needs to be replicated, particularly in studies with more comprehensive bone density evaluation.

Association of type 2 diabetes genetic variants with breast cancer survival among Chinese women.

OBJECTIVE: To evaluate whether the genetic susceptibility of T2D was associated with overall survival (OS) and disease-free survival (DFS) outcomes for breast cancer (BC). METHODS: Included in the study were 6346 BC patients who participated in three population-based epidemiological studies of BC and were genotyped with either GWAS or Exome-chip. We constructed a genetic risk score (GRS) for diabetes using risk variants identified from the GWAS catalog (http://genome.gov/gwastudies) that were associated with T2D risk at a minimum significance level of P ≤ 5.0E-8 among Asian population and evaluated its associations with BC outcomes with Cox proportional hazards models. RESULTS: During a median follow-up of 8.08 years (range, 0.01-16.95 years), 1208 deaths were documented in 6346 BC patients. Overall, the diabetes GRS was not associated with OS and DFS. Analyses stratified by estrogen receptor status (ER) showed that the diabetes GRS was inversely associated with OS among women with ER- but not in women with ER+ breast cancer; the multivariable adjusted HR was 1.38 (95% CI: 1.05-1.82) when comparing the highest to the lowest GRS quartiles. The association of diabetes GRS with OS varied by diabetes status (P for interaction <0.01). In women with history of diabetes, higher diabetes GRS was significantly associated with worse OS, with HR of 2.22 (95% CI: 1.28-3.88) for the highest vs. lowest quartile, particularly among women with an ER- breast cancer, with corresponding HR being 4.59 (95% CI: 1.04-20.28). No significant association between the diabetes GRS and OS was observed across different BMI and PR groups. CONCLUSIONS: Our study suggested that genetic susceptibility of T2D was positively associated with total mortality among women with ER- breast cancer, particularly among subjects with a history of diabetes. Additional studies are warranted to verify the associations and elucidate the underlying biological mechanism.

Dual specificity phosphatase 4 gene expression in association with triple-negative breast cancer outcome.

Triple-negative breast cancer (TNBC) is an aggressive cancer with limited treatment options. Dual specificity phosphatase 4 (DUSP4) has recently been suggested as a potential marker of chemotherapy resistance for TNBC. DUSP4 gene expression levels were measured in breast cancer tissue from 469 TNBC patients aged 20-75 years who participated in the Shanghai Breast Cancer Survival Study, and their association with recurrence/breast cancer mortality and total mortality was evaluated. Information on breast cancer diagnosis, treatment, and disease progression was collected via medical chart review and multiple in-person follow-up surveys. A Cox regression model was applied in the data analyses. Over a median follow-up of 5.3 years (range: 0.7-8.9 years), 100 deaths and 92 recurrences/breast cancer deaths were documented. Expression levels of transcript variant 1 (NM_001394) and transcript variant 2 (NM_057158) of the DUSP4 gene were studied and were highly correlated (r = 0.76). Low DUSP4 expression levels, particularly of variant 1, were associated with both increased recurrence/breast cancer mortality and increased overall mortality. Hazard ratios with adjustment for age at diagnosis and TNM stage associated with below versus above the median expression level were 1.97 (95 % confidence interval (CI): 1.27-3.05) for recurrence/breast cancer mortality and 2.09 (95 % CI: 1.38-3.17) for overall mortality. Additional adjustment for expression levels of MKI67 and TP53, common treatment types, breast cancer subtype, and grade did not materially alter the observed associations. Low DUSP4 expression levels predict recurrence and mortality in TNBC patients independently from known clinical and molecular predictors.

Menopausal symptoms among breast cancer patients: a potential indicator of favorable prognosis.

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.

Performance of breast cancer screening methods and modality among Chinese women: a report from a society-based breast screening program (SBSP) in Shanghai.

To evaluate the screening performance of individual and combined use of clinical breast examination, ultrasonography and mammography in Chinese women, we conducted a biennial breast cancer screening program among 14,464 women aged 35 to 74 years old who lived in Qibao County, Minhang district of Shanghai, China, between May 2008 and Sept 2012. All participants were submitted to clinical breast examination, and then women with positive results and all women at age of 45-69 years old were preformed breast ultrasonography and mammography. The examination results were compared against pathological findings as the gold standard of reference. A total of 66 women were diagnosed with breast cancer in the two rounds of the screening, yielding an incident rate of 194 per 100,000 person-years. The sensitivity of clinical breast examination, ultrasonography and mammography alone were 61.4%, 53.7% and 67.3%, respectively. While mammography performed better in elder age groups and hormone receptor positive disease groups, ultrasonography had a higher sensitivity in younger age group and did not differ in sensitivity by estrogen receptor or progesterone receptor status. Combined use of the two imaging examinations increased the sensitivity in almost all age groups, but had a higher sensitivity in hormone receptor positive cancers than in those negative. Our results suggest that the Qibao modality is an effective strategy for breast cancer screening among Chinese women, especially for early detection of elder and hormone receptor positive breast cancer.

[Recent incidences and trends of childhood malignant solid tumors in Shanghai, 2002-2010].

OBJECTIVE: To examine the recent incidences and trends of childhood malignant solid tumors in Shanghai. METHOD: Data from the population-based Shanghai Cancer Registry and related retrospective survey were used to analyze the patterns of incidence and trends of malignant solid tumors diagnosed between 2002 and 2010 in children aged 0-14 years. The distributions of incidences were described according to gender, age and cancer types which were classified according to International Classification of Childhood Cancer (ICCC). Annual age-standardized rates (ASRs) were adjusted by the world standard population. Approximate confidence intervals for standardized rate ratios (SRR) based Poisson distribution test-based methods were used to assess changes in incidence over the period 2002 - 2006 and 2007 - 2010. RESULT: (1)A total of 868 cases of childhood malignant solid tumors were diagnosed in Shanghai during 2002 - 2010, accounting for 65.8% of all childhood cancers. The ASR of 2002 - 2010 was 80.2 per million for all solid tumors. (2) The ASR was higher in boys (86.3 per million) than in girls (73.8 per million) with SRR 1.2 (95%CI 1.0 - 1.3). Incidence rate was the highest in the first five years of life with 93.4 per million. The age-specific incidence rates in 5 - 9 and 10 - 14 age groups were 65.2 and 79.3 per million, respectively. (3) CNS tumors, lymphomas, germ cell tumors, neuroblastoma, and soft tissue sarcomas were the top 5 most common solid tumors in children, with the incidence rate of 23.8, 11.0, 7.8, 7.7 and 6.8 per million, respectively. The patterns of subgroups varied in different age groups. Blastomas, such as neuroblastoma, retinoblastoma, were more common in the children aged 0 - 4 years, whereas epithelial carcinomas and bone tumors developed more frequently in elder children aged 10 - 14 years. (4) Compared with the ASR in 2002 - 2006, the ASR for both genders in 2007 - 2010 had no substantial changes (78.7 per million in 2002 - 2006 and 82.9 per million in 2007 - 2010). However, among boys, the incidence rate in 2007 - 2010 was significantly higher than that in 2002 - 2006 with SRR 1.2 (95%CI: 1.0 - 1.4). For specific subgroups of cancer, there were no substantial changes. Some cautions should be taken when interpreting results involving a small number of cases per year and those with wide 95% confidence intervals. CONCLUSION: The incidence rate of pediatric malignant solid tumors among males was higher than females during 2002 - 2010, and it differed among different age groups with the highest in the first five years of life. CNS tumor was the most common type of solid tumors in children. This was a unique characteristics comparing with adult reflected in disease spectrum and age of onset. The patterns of incidence and its trends for childhood malignant solid tumors in Shanghai could provide a basis for etiologic research and preventive interventions. The findings also suggest an urgent need for longer population-based surveillance to verify the pattern and changing trends.

Exercise after diagnosis and metabolic syndrome among breast cancer survivors: a report from the Shanghai Breast Cancer Survival Study.

Metabolic syndrome (MetS) is an established risk factor for cardiovascular diseases and mortality. Limited data are available on the prevalence of MetS and its association with exercise among breast cancer survivors. The present study included 1,696 breast cancer survivors from the Shanghai Breast Cancer Survival Study, a population-based prospective cohort study conducted between April 2002 and October 2011 in Shanghai, China. All women had a physical examination taken at study clinic approximately 60 months post-diagnosis. Exercise was assessed at approximately 6, 18, 36, and 60 months post-diagnosis. Information on medical history, tumor characteristics, cancer treatment, anthropometrics, and lifestyle was collected at study enrollment. Associations between exercise and MetS at 60 months post-diagnosis were evaluated with multivariable logistic regression models. The mean age of the study population was 56.68 at 60-month survey, and the mean follow-up since cancer diagnosis was 63.66 months. The prevalence of MetS using National Cholesterol Education Program Adult Treatment Panel III criteria at approximately 60 months after diagnosis was 33.14%. Among overweight and obesity breast cancer survivors (body mass index (BMI) ≥ 25 kg/m(2) at baseline), the prevalence was 55.18%. The most common type of exercise in this population was walking (45.40%) at baseline. Exercise participation between 6 and 60 months post-diagnosis was inversely associated with the prevalence of MetS with the adjusted odds ratio (OR) for exercise participation of ≥ 3.5 h/week (30 min/day) being 0.69 (95% confidence interval (CI) 0.48-0.98). In addition consistent exercise participation reduced the prevalence of MetS (adjusted OR 0.70 (95% CI 0.50-1.00). Associations of exercise with MetS were not modified by baseline waist circumference, BMI, comorbidity, baseline menopausal status, TNM stage, cancer treatment, or ER/PR status (p interactions > 0.05). Regular and persistent exercise after cancer diagnosis, even at low-to-moderate intensity level, decreases the prevalence of MetS among long-term breast cancer survivors.

Comorbidities and breast cancer survival: a report from the Shanghai Breast Cancer Survival Study.

We investigated the association of major comorbidities with breast cancer outcomes using the Shanghai Breast Cancer Survival Study, a population-based, prospective cohort study of Chinese women diagnosed with breast cancer. Analyses included 4,664 women diagnosed with stage I-III incident breast cancer aged 20-75 years (median age = 51) during 2002-2006. Women were interviewed at 3-11 months post-diagnosis (median = 6.4) and followed up by in-person interviews and linkage with the vital statistics registry. Multivariable hazard ratios (HRs) and (95 % confidence intervals (CIs)) for the associations of comorbidities with breast cancer outcomes were estimated using Cox regression models. After a median follow-up of 5.3 years (range: 0.64-8.9), 647 women died (516 from breast cancer) and 632 recurrence/metastases were documented. The main comorbidities reported included: hypertension (22.4 %), chronic gastritis (14.3 %), diabetes mellitus (6.2 %), chronic bronchitis/asthma (5.8 %), coronary heart disease (5.0 %), and stroke (2.2 %). Diabetes was associated with increased risk of total mortality (adjusted HR: 1.40 (1.06-1.85)) and non-breast cancer mortality (adjusted HR: 2.64 (1.63-4.27)), but not breast cancer-specific mortality (adjusted HR: 0.98 (0.68-1.41)), adjusting for socio-demographics, clinical characteristics, selected lifestyle factors, and other comorbidities. Women with a history of stroke had a non-significant increased risk of total mortality (adjusted HR: 1.42 (0.91-2.22)) and a significant increased risk of non-breast cancer mortality (adjusted HR: 2.52 (1.33-4.78)), but not breast cancer-specific mortality (adjusted HR: 0.78 (0.38-1.62)). Overall, none of the comorbidities investigated were significantly associated with recurrence. In this large prospective cohort of breast cancer survivors, diabetes was significantly associated with increased risk of total and non-breast cancer mortality, and history of stroke was associated with increased risk of non-breast cancer mortality.

Polymorphisms in inflammation pathway genes and endometrial cancer risk.

BACKGROUND: Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. METHODS: To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P < 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls. RESULTS: Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. CONCLUSIONS: These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis.

Fruit, vegetable, and animal food intake and breast cancer risk by hormone receptor status.

The effects of diet on breast cancer are controversial and whether the effects vary with hormone receptor status has not been well investigated. This study evaluated the associations of dietary factors with risk for breast cancer overall and by the hormone receptor status of tumors among Chinese women. The Shanghai Breast Cancer Study, a large, population-based, case-control study, enrolled 3,443 cases and 3,474 controls in 1996-1998 (phase I) and 2002-2005 (phase II); 2676 cases had estrogen receptor (ER) and progesterone receptor (PR) data. Dietary intake was assessed using a validated, quantitative, food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from multivariate, polychotomous, unconditional logistic regression models. Total vegetable intake was inversely related to breast cancer risk, with an adjusted OR for the highest quintile of 0.80 (95% CI = 0.67-0.95; P trend = 0.02). Reduced risk was also related to high intake of allium vegetables (P trend = 0.01) and fresh legumes (P trend = 0.0008). High intake of citrus fruits and rosaceae fruits were inversely associated with breast cancer risk (P trend = 0.003 and 0.004, respectively), although no consistent association was seen for total fruit intake. Elevated risk was observed for all types of meat and fish intake (all P trend < 0.05), whereas intakes of eggs and milk were associated with a decreased risk of breast cancer (both P trend <0.05). There was little evidence that associations with dietary intakes varied across the 4 tumor subtypes or between ER+/PR+ and ER-/PR- tumors (P for heterogeneity >0.05). Our results suggest that high intake of total vegetables, certain fruits, milk, and eggs may reduce the risk of breast cancer, whereas high consumption of animal-source foods may increase risk. The dietary associations did not appear to vary by ER/PR status.