Insights Into Colorectal Cancer Screening: A Multidatabase Cohort Study of Over 1.5 Million Taiwanese.

INTRODUCTION: Colorectal cancer (CRC) remains a significant public health concern. This study aims to provide a comprehensive understanding of the effectiveness of fecal immunochemical test (FIT) screening on CRC incidence and mortality, leveraging the scale of over 1.5 million randomly selected Taiwanese and more than 11.7 million person-years of follow-up. METHODS: This prospective cohort study merges data from 3 robust Taiwanese health databases: the CRC screening program, cancer registration, and death registration databases. Incidence and mortality rates of CRC were calculated based on age, sex, urbanization, and past screening status. Cox proportional hazard models were used to assess the association between screening statuses and CRC incidence or mortality, adjusting for age, sex, and urbanization levels. Statistical analysis of the data was conducted in 2021-2022. RESULTS: FIT screening was associated with a 33% reduction in CRC incidence and a 47% reduction in mortality. The study identified a dose-response relationship between the fecal hemoglobin concentration (f-HbC) levels and CRC risk. Participants with consistent FIT-negative results had significantly reduced CRC incidence and mortality risks, while those with one or more positive FIT results faced increased risks. Notably, compliance with follow-up examinations after a positive FIT significantly lowered mortality risk. CONCLUSIONS: This large-scale study validates the efficacy of FIT screening in reducing CRC incidence and mortality. It offers a nuanced understanding of how various screening statuses impact CRC risks, thus providing valuable insights for public health strategies aimed at CRC prevention.

The Risk of Cancer-Associated and Radiotherapy-Associated Cardiovascular Diseases among Patients with Breast Cancer.

BACKGROUND: The cardio-related issues should be emphasized as the survival rates of breast cancer increased. We investigated the risk of coronary artery disease (CAD) and stroke due to breast cancer or radiotherapy. METHODS: In this retrospective cohort study, breast cancer patients diagnosed between 2007 and 2016 were recruited from Taiwan Cancer Registry Database and were followed until the end of 2018 by linking with the Taiwan National Health Insurance Database. The general population was randomly selected from the whole population in 2007. Standardized incidence ratios (SIR) were calculated to compare the risk of CAD and stroke between patients and the general population. Within the cohort, we included the patients diagnosed between 2011 and 2016. Cox proportional hazards model and subdistribution hazard function were used to investigate the associations of radiotherapy with the risk of CAD and stroke. RESULTS: Overall SIR of CAD was 0.82 (95% confidence interval [CI]: 0.78-0.86), while were 1.43 and 1.08 (95% CI: 1.30-1.55 and 1.00-1.16) 1 and 2 years after diagnosis, respectively. Overall SIR of stroke was 0.63 (95% CI: 0.60-0.67), the results were similar after considering the time since diagnosis. The adjusted hazard ratios (HR) for the associations of radiotherapy with CAD and stroke risk were 0.91 (95% [CI] = 0.76-1.09) and 0.84 (95% CI = 0.68-1.04), respectively. The results were similar by using subdistribution hazard function. CONCLUSIONS: The risk of CAD was higher within the first 2 years of breast cancer diagnosis. We found no association between radiotherapy and the risk of CAD and stroke.

Screening History and 7-Year Survival in 32,099 Colorectal Cancer Patients: A Population-Based Cohort Study.

Background: It is unclear whether colorectal cancer screening history, regardless of stage, is an independent predictor of survival, and if the screening advantage persists after diagnosis. 32 099 patients with colorectal cancer were enrolled in this population-based cohort study. Methods: We used data from the Taiwan Cancer Registry on patients with a first-time diagnosis of colorectal cancer between 2013 and 2015. In addition, we utilized data from a nationwide database of colorectal cancer screening programs to evaluate patients' screening histories, and sourced outcome data from the National Death Registry, tracking patients up to the last day of 2019. Results: Compared with fecal immunochemical testing (FIT)-positive patients with a follow-up examination, the adjusted hazard ratios (95% confidence intervals) for death from colorectal cancer were 1.40 (1.26-1.56) for FIT-positive patients without a follow-up examination, 1.63 (1.48-1.78) for FIT-negative patients, and 1.76 (1.65-1.89) for never screened patients. The adjusted hazard ratios for the FIT-positive patients with a follow-up examination increased when diagnosis was delayed by more than 12 months and were 1.2 after a 2-year delay. The adjusted hazard ratios for FIT-negative patients were approximately 2.0, decreased rapidly to 1.6, and stabilized after the 9th time-to-diagnosis month. Conclusion: In colorectal cancer patients, screening history prior to diagnosis is an independent prognostic factor, regardless of cancer stage or other variables. This study recommends that physicians take screening history into account during diagnosis to optimize follow-up and management for patients at higher risk.

Association between thyroid cancer and cardiovascular disease risk: a nationwide observation study.

Treatment with levothyroxine and radioiodine contribute alternative cardiovascular function in adults with thyroid cancer. The risks of long-term cardiovascular conditions among thyroid cancer patients is unknown. This study aimed to compare the incidence of coronary heart disease (CHD), ischemic stroke (IS), and atrial fibrillation (AF) among adults with thyroid cancer with that of the general population, especially when stratified by age (< 65 and ≥ 65 years old). This observational cohort study enrolled patients between January 1, 2011 and December 31, 2016 with a follow-up until December 31, 2018. This study analyzed the data of Taiwanese thyroid cancer patients registered on the National Taiwan Cancer Registry Database, with CHD and IS. SIR models were used to evaluate the association between thyroid cancer and CHD, IS, AF, and cardiovascular disease outcome, stratified by age and sex. SIR analyses were also conducted for both sexes, age groups (< 65, ≥ 65 years), and different follow-up years. After excluding 128 individuals (< 20 years or ≥ 85 years old) and with missing index data, 4274 eligible thyroid cancer patients without CHD history, 4343 patients without IS history, and 4247 patients without AF history were included for analysis. During the median follow-up of 3.5 (1.2) years among thyroid cancer patients, the observed number of new CHD events was 70; IS, 30; and AF, 20, respectively. The SIR was significantly higher for CHD (SIR, 1.57; 95% confidence interval [CI] 1.2-1.93) among thyroid cancer patients compared with the age- and sex-specific standardized population. However, the association between thyroid cancer and the risks of IS (SIR, 0.74; 95% CI 0.47-1), cardiovascular disease (SIR, 0.88; 95% CI 0.7-1.05), and atrial fibrillation (SIR, 0.74; 95% CI 0.42-1.06) were insignificant. Moreover, stratification by age < 65 or age ≥ 65 years old and by sex for CHD suggested that the diagnosis of thyroid cancer in the young may attenuate the CHD risk (SIR, 2.08; 95% CI 1.5-2.66), and the CVD risk was constant among both men (SIR, 1.63; 95% CI 1.03-2.24) and women (SIR, 1.53; 95% CI 1.06-1.99). The patients had persistent higher CHD risk for 5 years after cancer diagnosis. Thyroid cancer survivors have a substantial CHD risk, even at long-term follow-up, especially in those patients < 65 years old. Further research on the association between thyroid cancer and CHD risk is warranted.

The Risk of Ischemic Stroke in Head and Neck Cancer Patients and Those Who Were Treated with Radiotherapy: A Population-Based Cohort Study.

BACKGROUND: To investigate the standardized incidence ratios (SIR) of stroke in patients with head and neck cancer and their relationship to radiotherapy. METHODS: Patients with head and neck cancer ages 20-85 years were enrolled from 2007 to 2016 using the Taiwan Cancer Registry. The study endpoint was fatal and non-fatal ischemic stroke, ascertained by the National Health Insurance Research Database. Age- and sex-adjusted SIRs, categorized by 10-year age standardization, were used to compare the patients with head and neck cancer with a randomly selected 2,000,000 general population. We compared the risk of stroke in patients with head and neck cancer who received radiotherapy or surgery alone. Multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI) were obtained from Cox regression analysis with competing risk. RESULTS: Among 41,266 patients (mean age, 54.1 years; men, 90.6%) in the median follow-up period of 3.9 years, 1,407 strokes occurred. Compared with the general population, the overall SIR of stroke was 1.37 (95% CI, 1.30-1.44) in patients with head and neck cancer. In patients with head and neck cancer, the fully adjusted HR of stroke in those who received radiotherapy was 0.96 (95% CI, 0.83-1.10), compared with those who received surgery alone. CONCLUSIONS: Patients with head and neck cancer had a higher risk of fatal or non-fatal ischemic stroke. The risk of stroke was not higher in patients initially treated with radiotherapy. IMPACT: Oncologists should emphasize stroke prevention in all patients with head and neck cancer, not only in those who received radiotherapy.

Increased standardised incidence ratio of cardiovascular diseases among colorectal cancer patients.

PURPOSE: Evidence regarding the relationship between colorectal cancer and the risk of cardiovascular disease (CVD) is limited. Thus, in this study, we aimed to determine the standardised incidence ratio (SIR) of CVDs in colorectal cancer patients in Taiwan. METHODS: A population-based cohort study enrolling the incident colorectal cancer population based on the Cancer Registry Database from 2007 to 2016 was conducted (n = 94,233, mean age: 62.4 years, 43.0% women). New cases of CVD, including coronary heart disease and ischemic stroke, through 31 December 2018 were obtained from the National Health Insurance Research Database and National Death Registry. Compared with the general population (n = 1,977,659, mean age: 44.3 years, 49.6% women), age- and sex-specific SIRs for CVDs were calculated by the time since diagnosis. RESULTS: A total of 6852 cardiovascular events occurred in colorectal cancer patients during a median follow-up of 4.4 years. The SIR of CVD was highest in the first year after diagnosis (SIR: 1.45, 95% confidence interval: 1.39-1.50); however, this decreased to the same value as that of the general population in later years. Similar patterns were observed for the SIR of coronary heart disease. However, the SIR of ischemic stroke among colorectal cancer patients was low from the second year following cancer diagnosis. CONCLUSIONS: Colorectal cancer patients are at an increased risk of developing CVD, especially coronary heart disease, during the first 3 years following colorectal cancer diagnosis.

Ensemble forecasting of a continuously decreasing trend in bladder cancer incidence in Taiwan.

Bladder cancer is one of the most common malignancies involving the urinary system of about 1.65 million cases worldwide. To attain the 25 by 25 goal set by the World Health Organization (25% reduction in non-communicable diseases between 2015 and 2025), developing strategies to reduce cancer burdens is essential. The data of the study comprised the age-specific bladder cancer cases and total population numbers from age 25 to 85 and above from 1997 to 2016 in Taiwan. An ensemble age-period-cohort model was used to estimate bladder cancer incidence trends and forecast the trends to 2025. For men, the projected age-standardized incidence rates per 100,000 people in 2020 and 2025 are 13.0 and 10.4, respectively, with a 16.1% and 32.9% decrease projected from 2016 to 2020 and 2025, respectively. For women, the projected age-standardized incidence rates per 100,000 people in 2020 and 2025 are 4.7 and 3.7, respectively, with a 16.1% and 33.9% decrease projected from 2016 to 2020 and 2025, respectively. The age-specific bladder cancer incidence rates demonstrated a consistently downward trend after 2003 for all ages and both sexes. This study projects that the incidence rates of bladder cancer in Taiwan will continue to decrease, and more than a 25% reduction can be achieved from 2016 to 2025.

Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan.

Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01-8.83; OR = 2.04, 95% CI = 0.99-4.27; OR = 1.74, 95% CI = 1.00-3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated.

Identification of a liver cirrhosis signature in plasma for predicting hepatocellular carcinoma risk in a population-based cohort of hepatitis B carriers.

Liver cirrhosis is a critical state in the natural course of hepatocellular carcinoma (HCC). We sought to investigate the potential of in-depth proteomics to reveal plasma protein signatures that reflect common networks/pathways of liver cirrhosis, and to determine whether the cirrhosis-related signature in plasma is linked to the development of HCC among hepatitis B virus (HBV) carriers. We first compared plasma protein profiles using a 174-antibody microarray system between three groups of HBV carriers with different Child's grades of cirrhosis, which revealed a panel of 45 differentially expressed proteins with a high accuracy for discriminating Child's B/C. Ingenuity Pathway Analysis identified two main up-regulated networks connecting the 45 proteins that were most enriched for genes in the pathway of hepatic stellate cell activation. A parsimonious subset of 11 pathway-based proteins was then selected for quantification to correlate with HCC risk among 49 HCC cases and 50 controls in a nested case-control study within a 16-yr follow-up cohort of HBV carriers. A high risk score derived from a principal component analysis, which was used to extract the cluster structure of the 11 proteins, was associated with HCC (odds ratio = 4.83, 95% confidence interval: 1.26-18.56) even after adjustment for viral and clinical variables, implying the involvement of a pattern of coordinated proteins. Stepwise logistic regression on the 11 proteins revealed ICAM-2 as an independent predictor for HCC. These findings may give further insight into the pathobiology of hepatocarcinogenesis, allow testing of the cirrhosis-related plasma protein signature as a potential predictive biomarker for HCC.