Weight change and all-cause and cause-specific mortality: A 25-year follow-up study.

BACKGROUND: Whether the dynamic weight change is an independent risk factor for mortality remains controversial. This study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial (NIT) cohort. METHODS: Body weight of 21,028 healthy residents of Linxian, Henan province, aged 40-69 years was measured two times from 1986 to 1991. Outcome events were prospectively collected up to 2016. Weight maintenance group (weight change <2 kg) or stable normal weight group was treated as the reference. Cox proportional hazard model was performed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) to estimate the risk of mortality. RESULTS: A total of 21,028 subjects were included in the final analysis. Compared with the weight maintenance group, subjects with weight loss ≥2 kg had an increased risk of death from all-cause (HR All-cause  = 1.14, 95% CI: 1.09-1.19, P  <0.001), cancer (HR Cancer  = 1.12, 95% CI: 1.03-1.21, P  = 0.009), and heart disease (HR Heart diseases  = 1.21, 95% CI: 1.11-1.31, P  <0.001), whereas subjects with weight gain ≥5 kg had 11% (HR Cancer  = 0.89, 95% CI: 0.79-0.99, P  = 0.033) lower risk of cancer mortality and 23% higher risk of stroke mortality (HR Stroke  = 1.23,95% CI: 1.12-1.34, P  <0.001). For the change of weight status, both going from overweight to normal weight and becoming underweight within 5 years could increase the risk of total death (HR Overweight to normal = 1.18, 95% CI: 1.09-1.27; HR Becoming underweight = 1.35, 95% CI: 1.25-1.46) and cancer death (HR Overweight to normal = 1.20, 95% CI: 1.04-1.39; HR Becoming underweight = 1.44, 95% CI: 1.24-1.67), while stable overweight could increase the risk of total death (HR Stable overweight = 1.11, 95% CI: 1.05-1.17) and death from stroke (HR Stable overweight = 1.44, 95% CI: 1.33-1.56). Interaction effects were observed between age and weight change on cancer mortality, as well as between baseline BMI and weight change on all-cause, heart disease, and stroke mortality (all Pinteraction  <0.01). CONCLUSIONS: Weight loss was associated with an increased risk of all-cause, cancer, and heart disease mortality, whereas excessive weight gain and stable overweight were associated with a higher risk of stroke mortality. Efforts of weight management should be taken to improve health status. TRIAL REGISTRATION: https://classic.clinicaltrials.gov/ , NCT00342654.

Short-term and long-term effect of nutrition intervention in the Linxian Dysplasia Nutrition Intervention Trial and the reason for disappearance of the intervention effect: A cohort study.

BACKGROUND: The objective of this study was to determine the short-term and long-term effects of a nutrition intervention in using 37 years of follow-up data. METHODS: The Linxian Dysplasia Population Nutrition Intervention Trial was a randomized, double-blind, placebo-controlled trial with 7 years of intervention and 30 years of follow-up. The Cox proportional hazard model was used for analyses. Subgroup analyses were conducted in age and sex subgroups, and the 30 years of follow-up were divided into two 15-year early and late periods. RESULTS: The results at 37 years did not indicate any effects on mortality from cancers or other diseases. In the first 15 years, the intervention decreased the overall risk of gastric cancer deaths in all participants (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.58-1.00) and in the subgroup participants younger than 55 years (HR, 0.64; 95% CI, 0.43-0.96). In addition, in the group younger than 55 years (HR, 0.58; 95% CI, 0.35-0.96), the intervention decreased the risk of death from other diseases; and, in the group aged 55 years and older (HR, 0.75; 95% CI, 0.58-0.98), the intervention reduced the risk of death from heart disease. There were no significant results in the later 15 years, which indicated the disappearance of the intervention effect. Comparing demographic characteristics between those who died during the two periods, the participants who died later included more women, had a higher education level, had a lower smoking rate, were younger, and also more had a mild degree of esophageal dysplasia, representing a better lifestyle and health condition. CONCLUSIONS: Long-term follow-up indicated no effect of nutrition on deaths in a population with esophageal squamous dysplasia, further supporting the significance of continuous nutritional intervention for cancer protection. The pattern of protective effect of a nutrition intervention on gastric cancer in patients with esophageal squamous dysplasia was similar to that in the general population. Participants who died in the later period had more protective factors than those who died in the earlier period, contributing to the obvious effect of the intervention in early stage disease.

Performance of deep learning algorithms to distinguish high-grade glioma from low-grade glioma: A systematic review and meta-analysis.

This study aims to evaluate deep learning (DL) performance in differentiating low- and high-grade glioma. Search online database for studies continuously published from 1st January 2015 until 16th August 2022. The random-effects model was used for synthesis, based on pooled sensitivity (SE), specificity (SP), and area under the curve (AUC). Heterogeneity was estimated using the Higgins inconsistency index (I2). 33 were ultimately included in the meta-analysis. The overall pooled SE and SP were 94% and 93%, with an AUC of 0.98. There was great heterogeneity in this field. Our evidence-based study shows DL achieves high accuracy in glioma grading. Subgroup analysis reveals several limitations in this field: 1) Diagnostic trials require standard method for data merging for AI; 2) small sample size; 3) poor-quality image preprocessing; 4) not standard algorithm development; 5) not standard data report; 6) different definition of HGG and LGG; and 7) poor extrapolation.

Association between type of drinking water and upper gastrointestinal cancer incidence in the Linxian General Population.

BACKGROUND: This study aimed to explore the association between drinking water source and risk of upper gastrointestinal (UGI) cancer, including esophageal cancer (EC) and gastric cancer (GC), in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. METHODS: In this study, we used data from the Linxian NIT cohort, which included 29,584 healthy adults aged 40 to 69 years. Subjects were enrolled in April 1986 and followed up until March 2016. Tap water drinking status and demographic characteristics were collected at baseline. Subjects who drank tap water were treated as the exposed group. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model. RESULTS: A total of 5,463 cases of UGI cancer were identified during the 30-year follow-up period. After adjusting for multiple factors, the incidence rate of UGI cancer in participants who drank tap water was significantly lower compared with individuals in the control (HR = 0.91, 95% CI: 0.86-0.97). A similar association was observed between tap water drinking and EC incidence (HR = 0.89, 95% CI: 0.82-0.97). The association between drinking tap water and risk of UGI cancer and EC incidence did not vary across the subgroup by age and gender (All Pinteraction > 0.05). For EC incidence, an interaction effect was observed for riboflavin/niacin supplements and drinking water source (Pinteraction = 0.03). No association was observed between drinking water source and GC incidence. CONCLUSIONS: In this prospective cohort study in Linxian, participants who drank tap water had a lower risk of EC incidence. As a source of drinking water, use of tap water may reduce the risk of EC by avoiding exposure to nitrate/nitrite. Measures should be taken to improve the quality of drinking water in high-incidence areas of EC. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT00342654, 21/06/2006), and the trial name is Nutrition Intervention Trials in Linxian Follow-up Study.

Efficacy of PARP Inhibitor, Platinum, and Immunotherapy in BRCA-Mutated HER2-Negative Breast Cancer Patients: A Systematic Review and Network Meta-Analysis.

The optimal treatment regimen for breast cancer patients with gBRCA mutations remains controversial given the availability of numerous options, such as platinum-based agents, polymerase inhibitors (PARPis), and other agents. We included phase II or III RCTs and estimated the HR with 95% CI for OS, PFS, and DFS, in addition to the OR with 95% CI for ORR and pCR. We determined the treatment arm rankings by P-scores. Furthermore, we carried out a subgroup analysis in TNBC and HR-positive patients. We conducted this network meta-analysis using R 4.2.0 and a random-effects model. A total of 22 RCTs were eligible, involving 4253 patients. In the pairwise comparisons, PARPi + Platinum + Chemo was better than PARPi + Chemo for OS (in whole study group and in both subgroups) as well as PFS. The ranking tests demonstrated that PARPi + Platinum + Chemo ranked first in PFS, DFS, and ORR. Platinum + Chemo showed higher OS than PARPi + Chemo. The ranking tests for PFS, DFS, and pCR indicated that, except for the best treatment (PARPi + Platinum + Chemo) containing PARPi, the second and third treatments were platinum monotherapy or platinum-based chemotherapy. In conclusion, PARPi + Platinum + Chemo might be the best regime for gBRCA-mutated BC. Platinum drugs showed more favorable efficacy than PARPi in both combination and monotherapy.

Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study.

Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC). Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites. Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07). Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

Associations between serum glucose, insulin, insulin resistance and the risk of incident primary liver cancer or chronic liver disease mortality: a nested case-control study.

BACKGROUND: To evaluate the associations between pre-diagnostic levels of serum insulin, glucose and insulin resistance (HOMA-IR) and future risk of incident primary liver cancer (PLC) or chronic liver disease (CLD)-related mortality. METHODS: We used a nested case-control design to evaluate subjects over 22 years of follow-up. Glucose, insulin, and three markers of hepatitis B virus (HBV) and hepatitis C virus were measured in fasting baseline serum from 119 incident PLCs, 157 CLD-death cases and 512 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression to estimate the associations between insulin, glucose, HOMA-IR and the risk of PLC or CLD death. RESULTS: Compared with the lowest quartile of insulin, multivariable adjusted models showed that subjects in the highest quartile had elevated odds of developing PLC (ORQ4/Q1 = 2.42, 95% CI = 1.26-4.75, Ptrend = 0.007), particularly in HBV-positive subjects (Pinteraction = 0.040), and of CLD death (ORQ4/Q1 = 1.80, 95% CI = 1.02-3.21, Ptrend = 0.018). For glucose, in the HBV-positive group, subjects in the fourth quartile had an increased risk of PLC (ORQ4/Q1 = 2.18, 95% CI = 1.07-4.60, Ptrend = 0.009), and of CLD mortality (ORQ4/Q1 = 1.75, 95% CI = 0.95-3.28, Ptrend = 0.019). Subjects with the highest HOMA-IR values had a threefold risk of developing PLC (ORQ4/Q1 = 2.94, 95% CI = 1.54-5.87, Ptrend = 0.001), and a twofold risk of CLD death (ORQ4/Q1 = 2.20, 95% CI = 1.25-3.94, Ptrend = 0.005). CONCLUSIONS: We found that serum insulin and HOMA-IR could potentially be risk factors for PLC or CLD death.

Age at initial diagnosis and prognosis of breast cancer: a nationwide multicenter retrospective study in China.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Combined risk factors and risk of upper gastrointestinal cancer mortality in the Linxian general population.

We aimed to explore the association of combined risk factors with risk of death from upper gastrointestinal (UGI) cancer, including esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC) and gastric noncardia carcinoma (GNCC) in the Linxian Nutrition Intervention Trial (NIT) cohort. The NIT cohort included 29 584 healthy adults. A combined risk score (CRS) was calculated using a point system method based on 10 risk factors collected at baseline, including gender, smoking, alcohol drinking, body mass index, family history of UGI cancer, drinking tap water, tooth loss and consumption of fresh fruit, eggs and meat. Possible score ranged from 0 to 31, and higher score indicated as poorer health status. Subjects were divided into three groups by the CRS (<12 points, 12 to 20 points and >20 points). The group of CRS <12 points was considered as the reference. During the 30-year follow-up, we identified 4553 UGI cancer deaths. Compared to subjects with a CRS <12 points, the adjusted HRs for CRS of 12 to 20 points and >20 points were 1.69 (95% CI: 1.56-1.83) and 3.06 (95% CI: 2.82-3.33) for UGI cancer mortality, respectively (Ptrend < .001). Comparable associations were also observed for ESCC, GCC and GNCC mortality. Results remained similar across different age groups (Pinteraction > .05). All HRs observed in the second half follow-up period were stronger than that observed in the first half follow-up period. Our study indicated that higher CRS was associated with increased risk of UGI cancer mortality. Appropriate measures should be taken to reduce unhealthy lifestyles.

Mortality after multivitamin supplementation: Nearly 35-year follow-up of the randomized Linxian Dysplasia Nutrition Intervention Trial.

BACKGROUND: The objective of this study was to update the association between multivitamin supplementation and total or cause-specific mortality in a population with a high prevalence of undernutrition in China. METHODS: The Linxian Dysplasia Nutrition Intervention Trial was a randomized, double-blind, placebo-controlled trial in which 3318 persons aged 40-69 years with esophageal squamous dysplasia were assigned to receive daily multivitamin supplementation or a placebo for 6 years and were followed for 29 years. The primary outcome was esophageal/gastric cardia cancer mortality. The data were analyzed with Cox proportional hazards regression models. Subgroup analyses were performed by common characteristics such as age and gender. RESULTS: The cumulative total mortality was 83.5%. Multivitamin supplementation did not affect total or cause-specific mortality in the participants as a whole (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03). Subgroup analyses showed that no association between multivitamin supplementation and all-cause mortality was observed in men (HR, 0.90; 95% CI, 0.81-1.01), women (HR, 1.01; 95% CI, 0.91-1.12), younger participants (HR, 0.97; 95% CI, 0.87-1.08), or older participants (HR, 0.94; 95% CI, 0.85-1.04). Significant reductions in heart disease mortality (HR, 0.64; 95% CI, 0.47-0.87) and cerebrovascular disease mortality (HR, 0.74; 95% CI, 0.56-1.00) were seen in older men. In a subgroup of younger men and a subgroup of moderate or severe dysplasia, subjects receiving multivitamin supplementation had a lower risk of esophageal/cardia cancer mortality (HR for younger men, 0.76; 95% CI, 0.58-0.99; HR for moderate or severe dysplasia, 0.76; 95% CI, 0.58-1.00). No association between multivitamin supplementation and any cause-specific mortality was observed in a mild dysplasia population. CONCLUSIONS: Multivitamin supplementation in a population with esophageal squamous dysplasia was not associated with the risk of total mortality in the 35-year follow-up of this randomized controlled trial. In light of this and previous trials, multivitamin supplements should be used thoughtfully to improve health status of populations with esophageal squamous dysplasia. LAY SUMMARY: Multivitamin supplementation is common, yet its effect on mortality is unclear. The aim of this study was to update the long-term effects of multivitamin supplementation on total and cause-specific mortality during nearly 35 years of follow-up in the Linxian Dysplasia Nutrition Intervention Trial in China. Multivitamin supplementation in a population with esophageal squamous dysplasia was not associated with the risk of total mortality in the 35-year follow-up of this randomized controlled trial, and this indicates that multivitamin supplements should be used thoughtfully to improve health status.

The Association Between Family History of Upper Gastrointestinal Cancer and the Risk of Death from Upper Gastrointestinal Cancer-based on Linxian Dysplasia Nutrition Intervention Trial (NIT) Cohort.

Objective: Explore the influence of family history of upper gastrointestinal (UGI) cancer on UGI cancer death, based on the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort. Methods: Family history of UGI cancer was defined as at least one first-degree relative (parent, child, or sibling) had a history of esophageal or gastric cancer. Cancer death was carried out by ICD-10 code. Family history information was collected at baseline and cancer deaths were assessed at each annual follow-up. The COX proportional risk model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). We compared the positive family history group with the negative to determine the risk of family history on UGI cancer death. The effect of category of relatives, number of relatives with UGI cancer, and diagnosis age of relatives on the UGI death risk were further analyzed. Interaction and stratification analyses were done to see the subgroup effects. Sensitivity analyses were also conducted by exclusion of individuals who were followed up less than three years. We considered controlling of covariates including: gender, age (continuity), community, education level, number of siblings (continuity), BMI (continuity), smoking, alcohol use, fresh fruit intake, fresh vegetable intake, hot beverage intake, edible oil intake, meat intake, and moldy staple food intake. All food intake variables were converted into categorical variables. Results: From1985 to2015, we followed up total 3,318 individuals with 898 UGI cancer deaths (537 from ESCC, 77 from GNCC, and 284 from GCC). In a single factor analysis, family history of UGI cancer increased the risk of death of esophageal squamous cell carcinoma (ESCC) by 27% (HR=1.270, 95%CI1.072-1.504). No associations were observed in gastric cardia carcinoma (GCC) and gastric non-cardia carcinoma (GNCC). After adjusting for multi-factor, a family history of UGI cancer risk of death increased by 31.9% from ESCC (HR=1.319,95%CI:1.110-1.567). Subgroup analysis of different types of relatives with UGI cancers, UGI cancers in the mother (HR=1.457,95%CI:1.200-1.768), brother (HR=1.522,95%CI:1.117-2.073), and sister (HR=1.999,95%CI:1.419-2.817) were independent risk factors for ESCC death, while the father was not. In addition, 2 relatives with UGI cancer (HR=1.495, 95%, CI:1.110-2.013) and ≥3 relatives with UGI cancer (HR=2.836, 95%CI:1.842-4.367) significantly increased the risk of ESCC death, and the trend test was statistically significant (P<0.001). Relatives' diagnostic age of 51-60 years (HR=1.322, 95%CI:1.046-1.672) and 41-50 years (HR=1.442, 95%CI:1.078-1.930) were the risk factors for ESCC death, with statistical significance in the trend test (P=0.010). No statistically significant result of the family history effect on the risk of death from GCC or GNCC was found. Sensitivity analysis of 80% of subjects, randomly selected, did not change the results. Conclusion: A family history of UGI cancer may predict the risk of death from ESCC but not from GCC or GNCC. UGI cancer in the mother may predict the risk of death from ESCC, but not father, which indicates gender differences. Gender and smoking are the interaction items with family history in a similar extent. In the subgroup, the risk of ESCC death is more distinct by family history in younger, female, and better-lifestyle individuals, which indicates the unique role of genetic factors.

A Nomogram to Accurately Identify Pancreatic Neuroendocrine Tumors Metastasizing to Distant Organs: A Study Based on Two National Population-Based Cohorts From the United States and China.

Background: Distant organ metastasis is the leading cause of death in pancreatic neuroendocrine tumor (pNET) patients. In the present study, we aimed to develop and validate a nomogram that could accurately identify pNET metastasizing to distant organs. Methods: The cases extracted from the Surveillance, Epidemiology, and End Results (SEER) program were assigned to the training cohort and validation cohort. The cases from the Chinese Gastrointestinal Neuroendocrine Tumors program were assigned to the external validation cohort. The strategy was developed with the support of a nomogram, and the predictive value of this strategy was evaluated by the receiver operating characteristic (ROC) curve analysis. Results: In total, 2024 American cases were involved in the present study. Besides, 1450 and 574 patients were allocated into training and internal validation cohorts, respectively. In addition, 122 Chinese patients were assigned to the external validation cohort. The results of the univariate logistic regression analysis suggested that tumor grade, tumor size, and the number of metastatic lymph nodes were the risk of metastasis to distant organs, and these 3 clinicopathological characteristics were used to develop the nomogram. We observed that the accuracy of the nomogram for predicting metastasis to distant organs was 0.797, 0.819, and 0.837 in the training cohort, internal validation cohort, and external validation cohort, respectively. Conclusions: A predictive nomogram was developed and validated, and it showed an acceptable performance in predicting metastasis to distant organs. The results will enable clinicians to identify pNETs, metastasizing to distant organs, and develop an effective individualized therapeutic strategy for these patients.

Relationships between serum iron and liver diseases in nutrition intervention trials: A nested case-control study.

BACKGROUND: Serum iron is associated with the risk of several diseases. However, limited prospective studies have been performed between serum iron and the subsequent risk of chronic liver disease (CLD) and primary liver cancer (PLC) incidence. METHODS: We performed a nested case-control study using data from the Linxian Nutrition Intervention Trials among participants who developed PLC incidence or died from CLD over 22-years of follow-up. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of PLC incidence or CLD death in different quintile of baseline serum iron using logistic regression. RESULTS: Individuals with serum iron in the highest quintile, compared to those in the second quintile (the reference), had an increased risk of CLD mortality (OR=2.02, 95% CI=1.27-3.27, Ptrend=0.011). The association was stronger among HCV-positive participants (Pinteraction=0.005). For PLC incidence, the risk estimates were above one, but not statistically significant (all P > 0.05). CONCLUSIONS: A significant positive association was found between serum iron and the risk of CLD-related mortality, especially in HCV-positive subjects. Our results suggest that serum iron plays a risk role in CLD death but not in PLC incidence.

Combined Lifestyle Factors and Risk of All-Cause and Cause-Specific Mortality Among Participants in the Linxian Nutrition Intervention Trial: A Cohort, Observational Study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Comparisons of Treatment for HER2-Positive Breast Cancer between Chinese and International Practice: A Nationwide Multicenter Epidemiological Study from China.

OBJECTIVE: To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice. METHODS: This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II-IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall's correlation coefficient = 0.3, P < 0.0001), while no prohibitive variables among clinical characteristics were detected. CONCLUSION: Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889.

Profile, treatment patterns, and influencing factors of anthracycline use in breast cancer patients in China: A nation-wide multicenter study.

BACKGROUND: Anthracycline-based chemotherapy (ABC) is one of the standard therapies against breast cancer. However, few guidelines are currently available to optimize the use of ABC. Therefore, the present analysis aimed at determining the profile and treatment patterns of ABC and the association of clinicopathological characteristics with ABC selection. METHODS: We retrospectively analyzed the data of a nation-wide multicenter epidemiological study, which collected the medical records of breast cancer patients receiving chemotherapy in different settings from seven geographic regions in China (NCT03047889). RESULTS: In total, 3393 patients were included, with 2917 treated with ABC. Among them, 553 (89.8%), 2165 (81.7%), and 814 (25.7%) were subjected to ABC as neoadjuvant, adjuvant, and advanced chemotherapy, respectively. The most frequently used regimens were anthracycline-taxane-based combinations for neo- and adjuvant chemotherapy, along with taxanes and oral fluorouracils for the palliative stages. In the overall cohort, patients aged < 40 or 40-65 (p < 0.001), in premenopause (p < 0.001), without comorbidities (p = 0.016), with invasive ductal carcinoma (p= 0.001), high lymph node involvement (p < 0.001), in the pTNM stage II, III, or IV versus stage I (p < 0.001), subjected to mastectomy (p < 0.001) or subjected to sentinel lymph node biopsy combined with axillary lymph node dissection (p = 0.044), or with a decreased disease-free survival (p < 0.001) were more likely to be recommended to ABC. CONCLUSION: Taken together, ABC remained the mainstay of breast cancer treatment, especially in neo and adjuvant therapy. ABC was mainly used as a combination therapy, and the correlation between influencing factors and ABC choice varied during different settings, indicating the preference and different perspectives of medication considered by medical oncologists regarding the use ABC in China.

Colorectal cancer in the Linxian China Nutrition Intervention Trial: Risk factors and intervention results.

BACKGROUND: Colorectal cancer (CRC) is among the most common cancers in economically developed countries and developing world. While dietary factors are associated with risk of CRC in the West and urban China, little is known about risk or protective factors in rural China. METHODS: The Linxian General Population Nutrition Intervention Trial (NIT) cohort was established over 30 years ago to test whether daily multivitamin/mineral supplements could reduce the incidence and mortality of esophageal/gastric cardia cancer. The cohort included a total of 29,553 healthy participants 40-69 years old who were randomly assigned to supplements or placebos via a 24 fractional factorial study design. We examined risk factors for the development of CRC as well as the effects of four different nutritional factors (Factor A: retinol, zinc; B: riboflavin, niacin; C: ascorbic acid, molybdenum; D: selenium, alpha-tocopherol, beta-carotene,) on CRC incidence following 5.25 years of supplementation in this randomized, placebo-controlled intervention trial. RESULTS: CRC risk increased with age and height as well as piped water usage, family history of CRC, and consumption of foods cooked in oil, eggs, and fresh fruits. No effect on CRC was seen for any of these four intervention factors tested in both genders, but CRC was reduced 37% in females who received Factor D (selenium/alpha-tocopherol/beta-carotene) (RR = 0.63, 95% CI = 0.43-0.92, P = 0.016) compared to females who did not receive Factor D. CONCLUSIONS: In this undernourished rural Chinese population, CRC risk factors in this Chinese cohort showed both similarities and differences compared to Western and urban Asian Chinese populations. Intervention results suggested a potential benefit for women supplemented with selenium/alpha-tocopherol/beta-carotene.

Family History and Risk of Upper Gastrointestinal Cancer in the Linxian General Population.

OBJECTIVE: The objective of this study was to investigate family history (FH) of upper gastrointestinal (UGI) cancer and risk of esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC), and gastric non-cardia carcinoma (GNCC) in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. Methods: This prospective analysis was conducted using the Linxian NIT cohort data. Subjects with FH of UGI cancer was treated as an exposed group while the remainders were considered as a comparison group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between FH of UGI cancer and risk of UGI cancer incidence and mortality were estimated using Cox proportional hazards models. RESULTS: There were 5,680 newly diagnosed UGI cancer cases during the follow-up period, with a total of 4,573 UGI cancer deaths occurred, including 2,603 ESCC, 1,410 GCC, and 560 GNCC deaths. A positive FH of UGI cancer was associated with a significantly increased risk of ESCC and GCC (Incidence: HRESCC = 1.45, 95%CI: 1.35-1.56; HRGCC = 1.27, 95%CI: 1.15-1.40; Mortality: HRESCC = 1.40, 95%CI: 1.30-1.52; HRGCC = 1.27, 95%CI: 1.14-1.42) after adjusting for age at baseline, gender, smoking status, alcohol drinking, education level, and frequency of fresh fruit and vegetable consumption. Subjects with FH in both parents had the highest risk of ESCC and GCC incidence (HRESCC = 1.65, 95%CI: 1.40-1.95; HRGCC = 1.42, 95%CI: 1.12-1.81) and deaths (HRESCC = 1.65, 95%CI: 1.38-1.97; HRGCC = 1.42, 95%CI: 1.09-1.85). Spouse diagnosed with UGI cancer did not increase the risk of any UGI cancers of the subjects. In subgroup analysis, FH of UGI cancer was shown to significantly increase the risk of GCC in non-drinkers (Incidence: HR = 1.31, 95%CI: 1.17-1.47; Mortality: HR = 1.33, 95%CI: 1.17-1.50). No associations were observed for risk of GNCC. Sensitivity analysis by excluding subjects who were followed up less than three years did not materially alter our results. CONCLUSION: Our data point to the role of the FH of UGI cancer to the risk of ESCC and GCC incidence and mortality. The influence of family history on the risk of UGI cancer varies from different types of family members.

Association between serum ferritin, incident primary liver cancer, and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: A nested case-control study.

BACKGROUND AND AIM: 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). METHODS: We performed a nested case-control study in the Linxian Nutrition Intervention Trials. Baseline serum ferritin was measured for 226 incident primary liver cancer cases, 281 CLD mortalities diagnosed, and 1061 age-matched, gender-matched, and trial-matched controls. We used multivariable logistic regression models to calculate odds ratios and 95% confidence intervals. Subgroup analysis and interaction tests were performed by age, gender, alcohol drinking, hepatitis B virus seropositivity (HBV+)/hepatitis C virus seropositivity (HCV+), and trial. RESULTS: Participants with serum ferritin in the highest quartile, as compared with those in the lowest quartile, had an increased risk of CLD mortality (odds ratio = 1.72, 95% confidence interval = 1.12, 2.64, P-trend < 0.01). Moreover, the association with higher serum ferritin was stronger among alcohol drinkers and those who were HCV+ (P-interaction < 0.05). For incident liver cancer, risk estimates were above one but were not statistically significant. CONCLUSION: In this study, higher levels of serum ferritin at baseline were associated with subsequent mortality from CLD, particularly if combined with alcohol drinking or viral hepatitis. Further work is warranted to confirm our findings.

ABO genotypes and the risk of esophageal and gastric cancers.

BACKGROUND: Blood type has been associated with the risk of gastric cancer, but few studies have examined the association with esophageal squamous cell carcinoma (ESCC). METHODS: We conducted a case-control study using genotyping data of Chinese individuals, including cases of 2022 ESCC, 1189 gastric cardia adenocarcinoma, 1161 gastric noncardia adenocarcinoma, and 2696 controls. Genetic blood type was imputed using three single nucleotide polymorphisms. We used logistic regression to examine the association between blood type and the risk of each cancer. RESULTS: Compared to blood type O, the risk of ESCC was significantly elevated for blood type B and AB, with the highest risk for type AB (OR, 95%CI: 1.34, 1.07-1.67). Analysis of genotype suggested that the association of ESCC was from carrying the B allele. Similarly, blood type was significantly associated with gastric noncardia adenocarcinoma (P < 0.001) with risk significantly elevated in type A (1.37, 1.14-1.65) and AB (1.44, 1.10-1.89) compared to type O. Blood type was not associated with gastric cardia adenocarcinoma (P = 0.13). CONCLUSIONS: This study provides novel insights into the association between blood type and the risk of ESCC and restricted previously observed association to only gastric noncardia cancer, providing important evidence to clarify the pattern of association and suggesting mechanisms of action.