Effectiveness of a single low-dose computed tomography screening for lung cancer: A population-based perspective cohort study in China.

The purpose of this perspective cohort study was to evaluate the effectiveness of low-dose computed tomography (LDCT) screening for lung cancer in China. This study was conducted under the China Urban Cancer Screening Program (CanSPUC). The analysis was based on participants aged 40 to 74 years from 2012 to 2019. A total of 255 569 eligible participants were recruited in the study. Among the 58 136 participants at high risk of lung cancer, 20 346 (35.00%) had a single LDCT scan (defined as the screened group) and 37 790 (65.00%) not (defined as the non-screened group). Overall, 1162 participants were diagnosed with lung cancer at median follow-up time of 5.25 years. The screened group had the highest cumulative incidence of lung cancer and the non-screened group had the highest cumulative lung cancer mortality and all-cause cumulative mortality. We performed inverse probability weighting (IPW) to account for potential imbalances, and Cox proportional hazards model to estimate the weighted association between mortality and LDCT scans. After IPW adjusted with baseline characteristics, the lung cancer incidence density was significantly increased (37.0% increase) (HR1.37 [95%CI 1.12-1.69]), lung cancer mortality was decreased (31.0% decrease) (HR0.69 [95%CI 0.49-0.97]), and the all-cause mortality was significantly decreased (23.0% lower) (HR0.77 [95% CI 0.68-0.87]) in the screened group. In summary, a single LDCT for lung cancer screening will reduce the mortality of lung cancer and all-cause mortality in China.

Yield and cost of government-organized colorectal cancer screening in young high-risk population in Northeast China.

Guidelines for colorectal cancer (CRC) screening recommend screening at age 40 for high-risk population in China. However, the yield and cost of CRC screening in younger population are lacking. This analysis aimed to evaluate the yield and cost of CRC screening in high-risk 40- to 54-year-olds. Individuals aged 40-54 years who were determined to have a high risk of CRC were recruited from December 2012 to December 2019. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the detection rate of colorectal lesions among the three age groups and further calculated number of colonoscopies needed to screen (NNS) to detect one advanced lesion and cost of each group. The detection rates of advanced colorectal neoplasm in men aged 45-49 years (OR = 2.00, 95% CI: 0.93-4.30) and 50-54 years (OR = 2.19, 95% CI: 1.04-4.62) were higher than that aged 40-44 years. The detection rates of colorectal adenoma in women aged 50-54 years was higher than that aged 40-44 years (OR = 1.64, 95% CI: 1.23-2.19). Among the male screening population, NNS and cost to detect one advanced lesion in participants aged 45-49 years were similar to that aged 50-54 years, saving approximately half endoscopic resources and financial expenses compared with screening that aged 40-44 years. From the perspective of screening results and costs, it might be beneficial to delay the starting age of screening by gender. This study may provide reference for optimizing CRC screening strategies.

Outcomes of upper gastrointestinal cancer screening in high-risk individuals: a population-based prospective study in Northeast China.

OBJECTIVES: The strategy for upper gastrointestinal cancer (UGC) screening has not yet been determined, especially in northeast China. DESIGN: The sample was from an ongoing prospective population-based cohort for cancer screening. PARTICIPANTS: This study belonged to the Chinese Urban Cancer Screening Program. The analysis was based on the recruitment of participants aged 40-74 in Northeast China from 2016 to 2017. Totally, 39 369 eligible participants were recruited, 8772 were evaluated to be at high risk for UGC, 1957 underwent endoscopy. OUTCOMES: χ2 test and multifactor logistic regression model was performed to analyse influencing factors of participation rate. Receiver operating characteristic curve analysis was applied to evaluate the diagnostic power of the high-risk assessment. The Cox regression model was used to estimate hazard ratio (HR) for the potential value. RESULTS: The high-risk rate was 22.28% and the participation rate of endoscopy screening was 22.31%. Factors such as age at 45-59 years, female sex, high level of education, occupation for professional and technical personnel, former drinking, secondary smoking, less physical activity, history of trauma or mental depression, history of upper gastrointestinal system disease and family history of UGC were associated with increased participation in endoscopy screening (all the p<0.05). There were five UGCs, 86 oesophageal precancerous lesions and 145 gastric precancerous lesions, and the detection rates were 0.26%, 4.39% and 7.41%, respectively. The detection rate for both oesophageal and gastric lesions increased with age and was higher for men than for women (all the p<0.05). After a 3-year follow-up, 30 UGCs had been diagnosed and the high risk of UGC increased the mortality risk ratio (HR: 1.90, 95% confidence interval (CI) 1.41 to 2.56). CONCLUSION: The participation rate and outcomes of UGC screening were promising in our study and will provide important reference for evaluating value of UGC screening in China.

The COmprehensive Score for financial Toxicity in China: Validation and Responsiveness.

CONTEXT: Financial toxicity is a priority concern faced by cancer patients and oncology providers. A validated instrument is important to measure this toxicity and improve health-related quality of life of patients. OBJECTIVES: To assess the validity and responsiveness of the Chinese version of the COmprehensive Score for financial Toxicity (COST) and to measure financial toxicity using the COST instrument in Chinese health care systems. METHODS: A longitudinal observational study was performed at three cancer centers from March 2017 to October 2018 for eligible patients. Construct validity was assessed by exploratory and confirmatory factor analysis. The convergent and discriminant validity was tested by examining the correlation coefficient. Responsiveness was tested using the standardized response mean and effect size. Associations between the financial toxicity and variables were assessed by multivariable linear analysis. RESULTS: There were 440 participants at baseline and 268 participants at 6-month follow up. A two-factor solution better represented the Chinese version of COST structure with good internal consistency and test-retest reliability. Convergent validity showed mild to moderate correlations between the domains of COST and the similar domains of Self-Perceived Burden Scale and Quality of Life Discriminant validity showed a low correlation between the COST and the subjective support of Social Support Rate Scale. Sensitivity to change at the sixth month showed effect sizes with global COST scores of 0.3. Multivariable analysis showed that age, household income, and health insurance were significantly associated with financial toxicity. CONCLUSIONS: The Chinese version of COST is a valid and clinically responsive instrument. The identified baseline variables can be used to provide evidence for a financial toxicity intervention study.

Correlation between hormone receptor status and depressive symptoms in patients with metastatic breast cancer.

Individual differences in depressive symptoms correlate with morbidity and outcomes in breast cancer patients. We evaluated the effect of hormone receptor (HR) status on depressive symptoms in 176 women with metastatic breast cancer at diagnosis. To assess depression, the women completed Self-Rating Depression Scale (SDS) questionnaires at baseline examination (T1), after 4 chemotherapy cycles (T2) and after 6 months (T3). At baseline examination, 45/176 (25.6%) patients were found to be at high or medium risk for depression (SDS score ≥0.6). Among these, depression was both prevalent in HR-positive patients and in HR-negative patients (64.4% versus 51.4%, P = 0.001). In multivariate model, HR positivity and higher depression risk were associated with poorer overall survival (25.0 months versus 32.0 months, P < 0.05). Patients at high/medium risk of depression were treated with the antidepressant agent fluoxetine (N = 23) or no drug (N = 22). SDS scores in patients treated with fluoxetine were lower after 4 chemotherapy cycles and after 6 months than in the control group (mean scores: T2, 0.61 versus 0.67, P = 0.001; T3, 0.56 versus 0.65, P < 0.001). No difference on SDS scores was found between patients with positive or negative HR status during fluoxetine treatment. These findings suggest hormone receptor status is associated with depressive symptoms in patients with metastatic breast cancer. Fluoxetine relieves depressive symptoms in these patients, regardless of hormone receptor status.

Cell-based immunotherapy with cytokine-induced killer (CIK) cells: From preparation and testing to clinical application.

Cell-based immunotherapy holds promise in the quest for the treatment of cancer, having potential synergy with surgery, chemotherapy and radiotherapy. As a novel approach for adoptive cell-based immunotherapy, cytokine-induced killer (CIK) cells have moved from the 'bench to bedside'. CIK cells are a heterogeneous subset of ex-vitro expanded, polyclonal T-effector cells with both natural killer (NK) and T-cell properties, which present potent non-major histocompatibility complex-restricted cytotoxicity against a variety of tumor target cells. Initial clinical studies on CIK cell therapy have provided encouraging results and revealed synergistic antitumor effects when combined with standard therapeutic procedures. At the same time, issues such as inadequate quality control and quantity of CIK cells as well as exaggerated propaganda were continuously emerging. Thus, the Ministry of Health in China stopped CIK cell therapy in May 2016, which was a major setback for the innovation of CIK cell-based immunotherapy. Thus, it is very important to modify technical criteria to develop a standardized operation procedure (SOP) and standardized system for evaluating antitumor efficacy in a safe way.

The potential of plasma miRNAs for diagnosis and risk estimation of colorectal cancer.

Circulating microRNAs (miRNAs) were recognized to be potential non-invasive biomarkers for colorectal cancer (CRC) detection and prediction. Meanwhile, the association of the expression of plasma miRNAs with the risk of CRC patients has rarely been analyzed. Therefore, we conducted this study to evaluate the value of plasma miRNAs for CRC diagnosis and risk estimation. Fasting blood samples from 100 CRC patients and 79 cancer-free controls were collected. Plasma miR-106a, miR-20a, miR-27b, miR-92a and miR-29a levels were detected by RT-qPCR. Sensitivity and specificity were employed to evaluate the diagnostic value of miRNAs for CRC. Univariate and multivariate logistic regression were employed to analyze the association between miRNAs expression and CRC risk. As results, miR-106a and miR-20a were elevated in the patients with CRC. The sensitivity of miR-106a was 74.00% and the specificity was 44.40%, while the cutoff value was 2.03. As for miR-20a, the sensitivity was 46.00% and specificity was 73.42% when employed 2.44 as cutoff value. High expression of plasma miR-106a increased CRC risk by 1.80 -fold. Plasma miR-106a and miR-20a may as noninvasive biomarkers for detecting the CRC. High expression of miR-106a associated with CRC risk.

Intronic and promoter polymorphisms of hMLH1/hMSH2 and colorectal cancer risk in Heilongjiang Province of China.

PURPOSE: Given that mismatch repair (MMR) system plays an important role in recognizing and removing insertion/deletion mutations which occur during DNA replication, common variants associated with impaired MMR system may thus increase risk of colorectal cancer (CRC). Therefore, we aimed to demonstrate the associations between common variants in two MMR genes (hMLH1 and hMSH2) and CRC risk. METHODS: We genotyped 10 intronic/promoter single-nucleotide polymorphisms (SNPs) of hMLH1 and hMSH2 in 451 CRC patients and 630 controls. Associations between genotypes and CRC risk were estimated using odds ratios and 95 % confidence intervals. Gene-gene interactions, as well as gene-environment interactions on CRC risk were also investigated. RESULTS: We found that IVS15-214T>C and IVS11 + 107A>G of hMSH2 were significantly associated with CRC risk. In dominant model, variant carriers of the two SNPs could decrease risk of CRC by 31 % (ORadj = 0.69, 95 % CI 0.53-0.91, p < 0.01) and 33 % (ORadj = 0.67, 95 % CI 0.47-0.95, p = 0.02), respectively. In addition, IVS7-212T>A, IVS11+183A>G and IVS8+719T>C of hMSH2 were associated with the susceptibility to colon cancer rather than rectal cancer. ATTTGGGT and TCTTAGAC haplotypes were associated with 44 and 45 % decreased risk of CRC, respectively, while ATTTGAGT and TTTCAGAC haplotypes were associated with 1.37-fold and 2.49-fold increased risk of CRC, respectively. There was a significant three-way gene-gene interaction among hMSH2 IVS11+107A>G, IVS11+183A>G and IVS8+719T>C (p < 0.01). Significant gene-environment interactions were observed between hMSH2 IVS15-214T>C and IVS11+107A>G and cereals consumption (both with p < 0.01). CONCLUSIONS: Our findings suggested that intronic SNPs, gene-gene and gene-environment interactions in hMSH2 might be associated with susceptibility to CRC.

Breastfeeding and ovarian cancer risk: a systematic review and meta-analysis of 40 epidemiological studies.

The present systematic review and meta-analysis was conducted to assess any association between breastfeeding and the risk of ovarian cancer. A systematic search of published studies was performed in PUBMED and EMBASE and by reviewing reference lists from retrieved articles through March 2013. Data extraction was conducted independently by two authors. Pooled relative risk ratios were calculated using random-effect models. Totals of 5 cohort studies and 35 case-control studies including 17,139 women with ovarian cancer showed a 30% reduced risk of ovarian cancer when comparing the women who had breastfed with those who had never breastfed (pooled RR = 0.70, 95% CI: 0.64-0.76; p = 0.00), with significant heterogeneity in the studies (p = 0.00; I2 = 76.29%). A significant decreasd in risk of epithelial ovarian cancer was also observed (pooled RR = 0.68, 95% CI: 0.61-0.76). When the participants were restricted to only parous women, there was a slightly attenuated but still significant risk reduction of ovarian cancer (pooled RR = 0.76, 95% CI: 0.69-0.83). For total breastfeeding duration, the pooled RRs in the < 6 months, 6-12 months and > 12 months of breastfeeding subgroups were 0.85 (95% CI: 0.77-0.93), 0.73 (95% CI: 0.65-0.82) and 0.64 (95%CI: 0.56-0.73), respectively. Meta-regression of total breastfeeding duration indicated an increasing linear trend of risk reduction of ovarian cancer with the increasing total breastfeeding duration (p = 0.00). Breastfeeding was inversely associated with the risk of ovarian cancer, especially long-term breastfeeding duration that demonstrated a stronger protective effect.

Association between main Caspase gene polymorphisms and the susceptibility and prognosis of colorectal cancer.

Caspase (CASP) 3, 8, 9 are important caspases in the apoptosis pathway and play important roles in development and progression of cancer. A case-control study with 451 colorectal cancer (CRC) patients and 631 cancer-free controls were carried out, and CRC patients followed up, to investigate the associations between three main polymorphisms and colorectal cancer risk and prognosis, and their potential interactions with environmental factors on CRC risk among Chinese people. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction-single strand conformation polymorphism sequencing. Odds ratio (OR), hazard ratio (HR) and their 95 % confidence intervals (CIs) were estimated with unconditional logistic-regression and Cox proportion hazard model. Individuals harboring the CASP8 -652 6N ins/del plus del/del genotype had a slightly lower risk for CRC compared those with ins/ins genotype (adjusted OR = 0.77, 95 % CI 0.59-0.99, P = 0.04). Significant associations between CASP3 -928 GG genotype and CASP9 -1263 GG genotype and reduced risk of rectal cancer were observed (adjusted OR = 0.56, 95 % CI 0.34-0.92, P = 0.02; adjusted OR = 0.59, 95 % CI 0.36-0.95, P = 0.03, respectively). There was a marginal significant association between CASP8 -652 6N ins/del polymorphism and CRC prognosis (ins/del versus ins/ins, adjusted HR = 0.69, 95 % CI 0.48-0.99, P = 0.04). These findings suggested these polymorphisms and their combinations with dietary factors may be associated with the development of CRC. CASP8 -652 6N ins/del polymorphism may be an independent survival predictor for CRC.