Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10−8, and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19–1.40) and P= 7.63 × 10−10. An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
Several studies have indicated that combinations of lifestyle and dietary factors are associated with risk of total mortality and death from cardiovascular disease and cancer, but limited data are available from long-term follow-up studies in China.This study was a observational cohort study. We prospectively examined the associations of combined lifestyle factors and risk of total and cause-specific mortality in the Linxian General Population Nutrition Intervention Trial (NIT) cohort that included 29,584 healthy adults. A points system method was used to calculate a combined risk score of five lifestyle factors, including smoking, alcohol drinking, body mass index, vegetable intake and fruit intake. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).Overall, adjusted hazard ratios for mortality increased progressively with an increasing combined risk score. Compared to individuals with a score of zero or one, HRs (95%CIs) for a score of five or above were 1.59 (1.44-1.75) for all-cause mortality, 1.67 (1.48-1.88) for heart disease, 1.69 (1.52-1.88) for stroke, and 1.34 (1.21, 1.47) for cancer. This association for mortality was seen consistently, regardless of gender and age at baseline.A higher combined risk score was positively associated with risk of total, heart disease, stroke, and cancer mortality. These findings could provide further evidence for the idea that healthy lifestyle is the optimal way to reduce the risk of premature death, and encourage behavior change.
<p>Table S1 shows the information of Linxian Nutrition Intervention Trials; Table S2 shows the correlation between sex hormones and SHBG; Table S3-S6 show the ORs by age, alcohol drinking, smoking, follow-up time subgroups; Table S7 shows that the ORs in General Population Trial.</p>
e12513 Background: We aimed to evaluate factors associated with receipt of chemotherapy, and to describe trends of chemotherapeutic regimens and agents in Chinese females with breast cancer. Methods: We retrospectively analyzed demographic and pathological data along with chemotherapeutic information of 4211 breast cancer patients randomly selected from representative hospitals of 7 traditional areas in China between 1999 and 2008. Results: Among the 4211 cases, a total of 3271 cases (77.7%) received adjuvant chemotherapy (ACT), 558 (13.3%) received neoadjuvant chemotherapy (NACT), and 392 (9.3%) received chemotherapy for metastatic disease. In adjuvant settings, age, stage, HR and HER2 status were independent factors affecting the use of ACT (P < 0.001). Frequencies of ACT in stage I, II and III cases were 69.1%, 83.2% and 93.9%, respectively. Frequencies of ACT in age groups of ≤ 39, 40-49, 50-59, 60-69 and ≥ 70 years were 84.2%, 81.9%, 79.5%, 65.6% and 28.3%, respectively. The percentage of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in ACT decreased from 51.2% to 1.3% between 1999 and 2008, and the use of regimens containing both anthracyclines and taxanes increased from 14.4% to 45.4% during the same period, while anthracycline-based (without taxanes) regimens increased during the first 5 years (from 15.3% to 54.5%) and decreased to 26.8% in 2008. Compared to earlier stage, more locally advanced patients received NACT (24.1% vs. 9.2%, p < 0.001). The percentage of NACT regimens containing both anthracyclines and taxanes increased from 2.4% to 43.8% between 1999 and 2008, while anthracycline-based (without taxanes) regimens increased in the first 6 years (from 24.4% to 70.4%) and decreased to 30.0% in 2008. In first-line chemotherapy, 87.5% of cases received combined chemotherapy. Among them, most received anthracyclines and taxanes (34.9%), followed by taxanes plus platinum (21.7%) and vinorelbine plus platinum (16.5%). Conclusions: Major changes have taken place in chemotherapy for early and metastatic breast cancer patients in China during this 10-year interval, which reflected the incorporation of key evidence and guidelines into Chinese medical practice.
Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case–cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case–control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR Q1:Q4 ) for GNCA in NIT was 1.35 (95% CI: 0.89–2.05; p ‐trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02–2.70; p ‐trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR Q1:Q4 = 2.00, 95% CI: 1.45–2.77; p ‐trend<0.001). In contrast, a lower risk of ESCC (NIT ESCC HR Q1:Q4 = 0.65, 95% CI: 0.45–0.92; p ‐trend = 0.02) was found in NIT. Low baseline ghrelin concentrations were associated with an increased risk for GNCA and GCA in the NIT and the SWHS. In contrast, low ghrelin concentrations at baseline were associated with a reduced risk of developing ESCC in the NIT. Ghrelin may be an early marker of future cancer risk for developing upper gastrointestinal cancer in regions of high incidence.
Several studies have indicated possible associations between age and the prognosis of breast cancer (BC), but limited data are available from hospital-based multicenter studies in China. This study aimed to explore the associations between age at initial diagnosis of BC and the risk of recurrence or metastasis among Chinese women with newly diagnosed advanced breast cancer (ABC) and provide treatment decision support for BC patients of different ages to medical workers.The medical records of patients newly diagnosed with ABC were obtained from 21 hospitals in seven geographic regions in China from 2012 to 2014. Patients' general information, clinicopathological features at first diagnosis, treatment information, and prognosis were retrospectively collected based on the self-designed case report form (CRF). Cox proportional hazards regression models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for the associations between age groups and the risk of recurrence and metastasis.A total of 1,852 cases were included in the final analysis. Age at initial diagnosis was shown to be significantly related to hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, molecular subtypes, and the number of lymph node metastasis (all P<0.05). Patients aged <35 years were more likely to have bone metastasis (45.6%). Patients aged ≥65 years had a lower percentage of receiving surgery (87.1%), adjuvant chemotherapy (61.3%), adjuvant radiotherapy (35.5%), and adjuvant endocrine therapy (30.6%) than the other groups (all P<0.05). Compared with patients aged <35 years, the risk of recurrence or metastasis in those aged 55-64 years was significantly higher (HRage 55-64 =1.24, 95% CI: 1.04-1.47), and the risk of bone metastasis and lung metastasis in those aged 35-44 years was lower (HRbone metastasis =0.74, 95% CI: 0.59-0.93; HRlung metastasis =0.70, 95% CI: 0.53-0.93). After adjusting for stage, grade, and molecular subtype, surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, adjuvant radiotherapy, adjuvant endocrine therapy, and family history of BC, patients aged 35-44 years still had a significantly reduced risk of bone metastasis and lung metastasis by 31% and 52%, respectively (HRbone metastasis =0.69, 95% CI: 0.48-0.98; HRlung metastasis =0.48, 95% CI: 0.31-0.74).Age at initial diagnosis is related to the clinicopathological characteristics and treatment pattern. Although the risk of site-specific metastasis varies by age, age is not an independent factor influencing the risk of total recurrence and metastasis. In accordance with current clinical practice guidelines for BC, however, precise treatment shall be chosen personally for patients whose ages at initial diagnosis are different.
Cancer stem-like cells have been identified in primary human tumors and cancer cell lines. Previously we found TM4SF1 gene was highly expressed in side population (SP) cells from esophageal squamous cell carcinoma (ESCC) cell lines, but the role and underlying mechanism of TM4SF1 in ESCC remain unclear. In this study, we observed TM4SF1 was up-regulated but miR-141 was down-regulated in SP cells isolated from ESCC cell lines. TM4SF1 could stimulate the self-renewal ability and carcinogenicity of esophageal cancer stem-like cells, and promote cell invasion and migration. In miR-141 overexpression cells, the expression of TM4SF1 was significantly reduced. We also found that overexpression of miR-141 could abolish the self-renewal ability and carcinogenicity of esophageal cancer stem-like cells and decrease cell invasion and migration by suppressing TM4SF1. Consequently, TM4SF1 is a direct target gene of miR-141. The regulation of TM4SF1 by miR-141 may play an important role in controlling self-renewals of esophageal cancer stem-like cells. It may also promote the development of new therapeutic strategies and efficient drugs to target ESCC stem-like cells.
Previous studies suggest that serum ferritin may be associated with higher risk of liver cancer. However, additional studies of the association are needed. It is also not clear whether serum ferritin is associated with mortality from chronic liver disease (CLD).
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