Cancer Incidence Characteristic Evolution Based on the National Cancer Registry in Taiwan

Huang, Yu‐Ting; Chen, Yu-Hung

doi:10.1155/2020/1408793

Cited by 24 publications

(23 citation statements)

References 53 publications

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“…The incidence rate of pancreatic cancer, which has the most unfavorable prognosis and survival rate, is also increasing in Taiwan. Finally, head and neck cancers have an incidence rate ten times greater in males than in females because of the habit of chewing betel nuts [35]. In a previous study, researchers demonstrated a significant correlation between TMB and the immune response across 27 solid tumor types [1].…”

Section: Discussionmentioning

confidence: 98%

Comprehensively Exploring the Mutational Landscape and Patterns of Genomic Evolution in Hypermutated Cancers

Lin

Yeh

Hsu

et al. 2021

Cancers

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Tumor heterogeneity results in more than 50% of hypermutated cancers failing to respond to standard immunotherapy. There are numerous challenges in terms of drug resistance, therapeutic strategies, and biomarkers in immunotherapy. In this study, we analyzed primary tumor samples from 533 cancer patients with six different cancer types using deep targeted sequencing and gene expression data from 78 colorectal cancer patients, whereby driver mutations, mutational signatures, tumor-associated neoantigens, and molecular cancer evolution were investigated. Driver mutations, including RET, CBL, and DDR2 gene mutations, were identified in the hypermutated cancers. Most hypermutated endometrial and pancreatic cancer patients carry genetic mutations in EGFR, FBXW7, and PIK3CA that are linked to immunotherapy resistance, while hypermutated head and neck cancer patients carry genetic mutations associated with better treatment responses, such as ATM and BRRCA2 mutations. APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) and DNA repair defects are mutational drivers that are signatures for hypermutated cancer. Cancer driver mutations and other mutational signatures are associated with sensitivity or resistance to immunotherapy, representing potential genetic markers in hypermutated cancers. Using computational prediction, we identified NF1 p.T700I and NOTCH1 p.V2153M as tumor-associated neoantigens, representing potential therapeutic targets for immunotherapy. Sequential mutations were used to predict hypermutated cancers based on genomic evolution. Using a logistic model, we achieved an area under the curve (AUC) = 0.93, accuracy = 0.93, and sensitivity = 0.81 in the testing set. The sequential patterns were distinct among the six cancer types, and the sequential mutation order of MSH2 and the coexisting BRAF genetic mutations influenced the hypermutated phenotype. The TP53~MLH1 and NOTCH1~TET2 sequential mutations impacted colorectal cancer survival (p-value = 0.027 and 0.0001, respectively) by reducing the expression of PTPRCAP (p-value = 1.06 × 10−6) and NOS2 (p-value = 7.57 × 10−7) in immunity. Sequential mutations are significant for hypermutated cancers, which are characterized by mutational heterogeneity. In addition to driver mutations and mutational signatures, sequential mutations in cancer evolution can impact hypermutated cancers. They characterize potential responses or predictive markers for hypermutated cancers. These data can also be used to develop hypermutation-associated drug targets and elucidate the evolutionary biology of cancer survival. In this study, we conducted a comprehensive analysis of mutational patterns, including sequential mutations, and identified useful markers and therapeutic targets in hypermutated cancer patients.

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Section: Discussionmentioning

confidence: 98%

Comprehensively Exploring the Mutational Landscape and Patterns of Genomic Evolution in Hypermutated Cancers

Lin

Yeh

Hsu

et al. 2021

Cancers

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“…Moreover, while stomach cancer is markedly prevalent in most East Asian countries, liver cancer is relatively common in Taiwan [ 43 , 44 ]. In this study, gastrointestinal cancer accounted for approximately 30%, which corresponded to the cancer epidemiology in Taiwan during the study period [ 45 ]. Unfortunately, the influence of metabolic depression on different site-specific cancers could not be studied in detail.…”

Section: Discussionmentioning

confidence: 99%

Lipid biomarkers and Cancer risk - a population-based prospective cohort study in Taiwan

et al. 2021

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Background Blood lipids are essential components for cellular growth. An inverse association between serum lipid levels and risk of cancer has led to a controversy among previous studies. The aim of this prospective cohort study was to investigate the association between blood lipids change and risk of cancer incidence. Methods A cohort of 4130 Taiwanese adults from the Taiwanese Survey on the Prevalence of Hypertension, Hyperglycemia, and Hyperlipidemia database underwent repeated examinations in 2002 and 2007. Six groups were established based on the combined baseline (lower/higher) and interval change (decreasing/stable/increasing) in plasma lipid levels. Multivariable Cox proportional hazard model was used to investigate the relationship between lipids change and all-cause cancer incidence. Results Two hundred and forty cancer events developed over a median follow-up of 13.4 years. Comparing these with individuals with decreasing lower-baseline lipid levels, cancer risk reduction was demonstrated in those with increasing lower-baseline total cholesterol (adjusted hazard ratio [aHR], 0.48; 95% confidence interval [CI], 0.27 to 0.85), low-density lipoprotein cholesterol (LDL-C; aHR, 0.56; 95% CI, 0.35 to 0.92), and non–high-density lipoprotein cholesterol (non-HDL-C) (aHR, 0.54; 95% CI, 0.31 to 0.92) levels. A decreased risk for cancer incidence also presented in participants with stable lower-baseline, decreasing and increasing higher-baseline LDL-C levels, and with decreasing and stable higher-baseline non-HDL-C levels. Conclusions The interval decline in lower-baseline total cholesterol, LDL-C, and non-HDL-C levels was linked to a higher risk for all-cause cancer incidence. More attention to a potential cancer risk may be warranted for an unexplained fall in serum lipids.

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“…In general, the TCR, with a 98.4% coverage, 93% histological verification, and 97.6% morphological verification (excluding liver), is the most important cancer registry in Taiwan. 17,18 Pancreatic cancer has an estimated coverage rate of approximately 60% for detailed cancer staging parameters in Taiwan since 2013. Admittedly, however, some limitations exist in the TCR, because some clinical factors and surgical variables may be missing or not documented in the database.…”

Section: Study Subjects In Taiwan As the Identification Setmentioning

confidence: 99%

Distinct Survival Outcomes in Subgroups of Stage III Pancreatic Cancer Patients: Taiwan Cancer Registry and Surveillance, Epidemiology and End Results registry

Chang

et al. 2021

Ann Surg Oncol

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Purpose Pancreatic cancer is one of the most malignant cancers with poor survival. The latest edition of the American Joint Committee on Cancer (AJCC) staging system classifies the majority of operable pancreatic cancer patients as stage-III, while dramatic heterogeneity is observed among these patients. Therefore, subgrouping is required to accurately predict their prognosis and define a treatment plan. This study conducts a cohort study to provide a more precise classification system for stage-III pancreatic cancer patients by utilizing clinical variables. Methods We analyzed survival using log-rank tests, univariate Cox-regression models, and Kaplan-Meier survival curves for stage-III pancreatic ductal adenocarcinoma (PDAC) patients from the Taiwan Cancer Registry (TCR). Patients were further divided into subgroups using classification and regression tree (CART) algorithm. All results were validated using the SEER database. Results Among stage-III PDAC patients, lymph node and tumor grade showed significant association with survival. Patients with N2 stage had higher mortality risks (hazard ratio [HR] = 2.30, 95% confidence interval [CI] 1.71–3.08, p < 0.0001) than N0 patients. Patients with grade 3 also had higher risk of mortality (HR = 3.80, 95% CI 2.25–6.39, p < 0.0001) than grade 1 patients. The CART algorithm stratified stage-III patients into four subgroups with significantly different survival rates. The median survival of the four subgroups was 23.5, 18.4, 14.5, and 9.0 months, respectively (p < 0.0001). Similar results were observed with SEER data. Conclusions Lymph node involvement and tumor grade are predictive factors for survival in stage-III PDAC patients. This new precise classification system can be used to guide treatment planning in advanced-stage pancreatic cancer.

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Cancer Incidence Characteristic Evolution Based on the National Cancer Registry in Taiwan

Cited by 24 publications

References 53 publications

Comprehensively Exploring the Mutational Landscape and Patterns of Genomic Evolution in Hypermutated Cancers

Comprehensively Exploring the Mutational Landscape and Patterns of Genomic Evolution in Hypermutated Cancers

Lipid biomarkers and Cancer risk - a population-based prospective cohort study in Taiwan

Distinct Survival Outcomes in Subgroups of Stage III Pancreatic Cancer Patients: Taiwan Cancer Registry and Surveillance, Epidemiology and End Results registry

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