BACKGROUND: Although change in the birth cohort effect on cancer mortality rates is known to be highly associated with the decreasing rates of age-standardized cancer mortality rates in Japan, the differences in the trends of cohort effect for representative cancer types among the prefectures remain unknown. This study aimed to investigate the differences in the decreasing rate of cohort effects among the prefectures for representative cancer types using age-period-cohort (APC) analysis. METHODS: Data on stomach, colorectal, liver, and lung cancer mortality for each prefecture and the population data from 1999 to 2018 were obtained from the Vital Statistics in Japan. Mortality data for individuals aged 50 to 79 years grouped in 5-year increments were used, and corresponding birth cohorts born 1920-1924 through 1964-1978 were used for analysis. We estimated the effects of age, period, and cohort on each type of mortality rate for each prefecture by sex. Then, we calculated the decreasing rates of cohort effects for each prefecture. We also calculated the mortality rate ratio of each prefecture compared with all of Japan for cohorts using the estimates. RESULTS: As a result of APC analysis, we found that the decreasing rates of period effects were small and that there was a little difference in the decreasing rates among prefectures for all types of cancer among both sexes. On the other hand, there was a large difference in the decreasing rates of cohort effects for stomach and liver cancer mortality rates among prefectures, particularly for men. For men, the decreasing rates of cohort effects in cohorts born between 1920-1924 and 1964-1978 varied among prefectures, ranging from 4.1 to 84.0% for stomach cancer and from 20.2 to 92.4% for liver cancers, respectively. On the other hand, the differences in the decreasing rates of cohort effects among prefectures for colorectal and lung cancer were relatively smaller. CONCLUSIONS The decreasing rates of cohort effects for stomach and liver cancer varied widely among prefectures. It is possible that this will influence cancer mortality rates in each prefecture in the future.
Aged ; Cohort Studies ; Colorectal Neoplasms/mortality* ; Female ; Humans ; Japan/epidemiology* ; Liver Neoplasms/mortality* ; Lung Neoplasms/mortality* ; Male ; Middle Aged ; Risk Factors ; Stomach Neoplasms/mortality*

PURPOSE: Colorectal cancer (CRC) is the third most common cancer in China and poses high morbidity and mortality. In recent years, increasing evidence has indicated that microRNAs played important functions in the occurrence and development of tumors. The purpose of this study was to identify the biological mechanisms of miR-362 in CRC. MATERIALS AND METHODS: Quantitative real-time PCR was carried out to assess the expression of miR-362 and SIX1. The Kaplan-Meier method was employed to evaluate the 5-year overall survival of CRC patients. The proliferative and invasive abilities of CRC cells were assessed by MTT and transwell assays. RESULTS: miR-362 was significantly decreased in CRC tissues and cell lines, compared to the normal tissues and normal cells. A significant connection was confirmed between the overall survival of 53 CRC patients and low expression of miR-362. Downregulation of miR-362 inhibited the proliferation and invasion through binding to the 3′-UTR of SIX1 mRNA in CRC. Additionally, we discovered that SIX1 was a direct target gene of miR-362 and that the expression of miR-362 had a negative connection with SIX1 expression in CRC. SIX1 could reverse partial functions in the proliferation and invasion in CRC cells. CONCLUSION: miR-362 may be a prognostic marker in CRC and suppress CRC cell proliferation and invasion in part through targeting the 3′-UTR of SIX1 mRNA. The newly identified miR-362/SIX1 axis provides insight into the progression of CRC.
Cell Line ; Cell Proliferation ; China ; Colorectal Neoplasms ; Down-Regulation ; Humans ; Methods ; MicroRNAs ; Mortality ; Real-Time Polymerase Chain Reaction ; RNA, Messenger

PURPOSE: Previous studies have reported conflicting results regarding the prognostic value of tumor sidedness in colon cancer. We investigated the oncologic impact of tumor location and examined whether recurrence patterns were related to tumor sidedness in colon cancer patients. METHODS: We identified stage I–III colon adenocarcinoma patients from a prospective colorectal cancer registry at Severance Hospital, Seoul, Korea, who underwent complete mesocolic excision between 2005 and 2012. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for predictors of cancer-specific survival (CSS), recurrence-free survival (RFS), and cumulative recurrence at specific anatomic sites were examined using Cox proportional hazard regression analysis. RESULTS: Overall, 1,912 patients, 1,077 (56.3%) with left-sided colon cancer (LCC), and 835 (43.7%) with right-sided colon cancer (RCC), at a median follow-up of 59 months, were eligible and included in the study. In univariate analysis, similar 5-year CSS and RFS were observed for LCC and RCC in the total patient population, and when stratified by stage for stage I and II patients. For stage III patients, an adjusted Cox regression analysis indicated that RCC patients had a higher risk of cancer-specific mortality (HR, 1.75; 95% CI, 1.07–2.86; P = 0.024) and recurrence (HR, 1.78; 95% CI, 1.22–2.60; P = 0.003). Furthermore, RCC was an independent predictor of peritoneal recurrence (HR, 1.86; 95% CI, 1.05–3.29; P = 0.031) in stage III patients. CONCLUSION: RCC correlated with worse CSS and RFS than LCC. In stage III patients, RCC correlated with increased risk of peritoneal recurrence. The reasons for these differences remain to be investigated.
Adenocarcinoma ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; Follow-Up Studies ; Humans ; Korea ; Mortality ; Prospective Studies ; Recurrence ; Seoul ; Treatment Outcome

PURPOSE: Liver resection is considered the only curative treatment modality for colorectal liver metastasis. The recurrence rate after hepatectomy is >50%. Two or more hepatectomies are applied to treat recurred metastases. We assessed the efficiency and feasibility of repeat hepatectomy and analyzed the prognostic factors after a repeat hepatectomy. METHODS: In total, 248 patients were diagnosed with recurred liver metastasis between January 2003 and May 2016. Second and third hepatectomies were performed in 70 and 7 patients, respectively. The other 171 patients did not undergo a repeat hepatectomy. Clinical features were collected from the medical records. We analyzed survival rates of the repeat hepatectomy group and the nonrepeat hepatectomy group. We also investigated factors affecting overall and disease-free survival of patients who received a repeat hepatectomy using univariate and multivariate analyses. RESULTS: Median overall survival was significantly higher in the repeat hepatectomy group than in the nonrepeat group (83.0 months vs. 25.0 months, P < 0.001). The morbidity and mortality rates of repeat hepatectomy were 9.1% and 0%, respectively. Median overall and disease-free survival of the repeat hepatectomy group were 62.0 and 51.0 months, respectively. The number of recurred tumors was the only significant factor for disease-free survival (P = 0.029). None of the factors affected overall survival. CONCLUSION: Repeat hepatectomy is necessary, effective, and safe for treating recurred colorectal liver metastasis. Repeat hepatectomy can be considered in patients with fewer than three recurred metastatic tumors.
Colorectal Neoplasms ; Disease-Free Survival ; Feasibility Studies ; Hepatectomy ; Humans ; Liver ; Medical Records ; Mortality ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Survival Rate

PURPOSE: Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival. MATERIALS AND METHODS: The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models. RESULTS: After adjustment for clinical characteristics and treatment factors, use of metformin was associated with better overall survival among colorectal cancer patients (hazards ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.88) and for all four types of cancer combined (HR, 0.75; 95% CI, 0.57 to 0.98). Ever use of insulin was associated with worse survival for all cancer types combined (HR, 1.89; 95% CI, 1.57 to 2.29) and for the four cancer types individually. Similar associations were seen for diabetic patients. Sulfonylureas use was associated with worse overall survival for breast or gastric cancer (HR, 2.87; 95% CI, 1.22 to 6.80 and HR, 2.05; 95% CI, 1.09 to 3.84, respectively) among diabetic patients. Similar association patterns were observed between diabetes medication use and cancer-specific survival. CONCLUSION: Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.
Breast ; Cohort Studies ; Colorectal Neoplasms ; Electronic Health Records ; Humans ; Insulin ; Lung ; Metformin ; Mortality ; Proportional Hazards Models ; Stomach Neoplasms

PURPOSE: Considering the health impact of obesity and cancer, it is important to estimate the burden of cancer attributable to high body mass index (BMI). Therefore, the present study attempts to measure the health burden of cancer attributable to excess BMI, according to cancer sites. MATERIALS AND METHODS: The present study used nationwide medical check-up sample cohort data (2002-2015). The study subjects were 496,390 individuals (268,944 men and 227,446 women). We first calculated hazard ratio (HR) in order to evaluate the effect of excess BMI on cancer incidence and mortality. Then, the adjusted HR values and the prevalence of excess BMI were used to calculate the population attributable risk. This study also used the Global Burden of Disease method, to examine the health burden of obesity-related cancers attributable to obesity. RESULTS: The highest disability-adjusted life year (DALY) values attributable to overweight and obesity in men were shown in liver cancer, colorectal cancer, and gallbladder cancer. Among women, colorectal, ovarian, and breast (postmenopausal) cancers had the highest DALYs values attributable to overweight and obesity. Approximately 8.0% and 12.5% of cancer health burden (as measured by DALY values) among obesity-related cancers in men and women, respectively, can be prevented. CONCLUSION: Obesity has added to the health burden of cancer. By measuring the proportion of cancer burden attributable to excess BMI, the current findings provide support for the importance of properly allocating healthcare resources and for developing cancer prevention strategies to reduce the future burden of cancer.
Body Mass Index ; Breast ; Cohort Studies ; Colorectal Neoplasms ; Delivery of Health Care ; Female ; Gallbladder Neoplasms ; Humans ; Incidence ; Korea ; Liver Neoplasms ; Male ; Methods ; Mortality ; Obesity ; Overweight ; Prevalence

Early detection and resection of neoplastic lesions are key objectives to diminish colorectal cancer mortality. Resection of superficial colorectal neoplasms, cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection have all been developed and used worldwide. The pocket-creation method facilitates the resection of tumors in difficult and routine locations. Early detection is the most important first step to maximize the benefits of recent advancements in endoscopic techniques. However, the detection of small, flat-shaped, or faded color lesions remains difficult. Linked color imaging, a novel multi-light technology, facilitates the recognition of minor differences in tissue by enhancing the color contrast between early colorectal neoplasms and surrounding normal mucosa in a bright field of view. The most striking feature of linked color imaging is its ability to display the color of early neoplastic lesions as distinct from inflammatory changes, both of which have similar “redness” when viewed using white light imaging. To increase the detection rate of neoplasms, linked color imaging should be used from the outset for endoscopic observation. Early detection of superficial colorectal tumors can result in decreased mortality from colorectal cancer and maintain a good quality of life for patients.
Colonoscopy ; Colorectal Neoplasms ; Endoscopy ; Humans ; Methods ; Mortality ; Mucous Membrane ; Quality of Life ; SNARE Proteins ; Strikes, Employee

Colorectal cancer (CRC) is one of the major reasons of mortality in the worldwide. There is clear evidence that some amino acids such as arginine can improve CRC and its complications. Hence, in this systematic review we evaluated the association between arginine intake and CRC improvement. We searched the PubMed, Scopus, ISI Web of Science, Cochrane library, and Google Scholar databases by using proper keywords to find the relevant literatures, published to March 2019. Nine human studies of 523 screened articles were included in present systematic review. The majority of studies have found a positive association between consumption of arginine and CRC improvement. Increased inducible nitric oxide (NO) synthase expression and subsequently increasing the NO concentration in the tumor and/or serum, after arginine intake may be responsible for these protective effects. Also, arginine consumption may reduce cell proliferation in CRC and it can enhance immune function after remove the tumor. Although the benefits of arginine consumption in CRC patients were reported in previous trials, the finding need replication in well-designed studies before final conclusion.
Amino Acids ; Arginine ; Cell Proliferation ; Colorectal Neoplasms ; Humans ; Mortality ; Nitric Oxide

BACKGROUND: The National Lung Screening Trial (NLST) and NELSON trial showed that low-dose chest computed tomography (LDCT) screening significantly reduced the mortality form lung cancer. Although cancer survivors are known to have high risk for second malignant neoplasm (SMN), the usefulness of LDCT screening for lung cancer in cancer survivors is not clear. METHODS: Between August 2016 and August 2017, 633 long-term colorectal cancer (CRC) survivors visited the survivorship clinic in Cancer Prevention Center, Yonsei Cancer Center, Seoul, Republic of Korea. We surveyed the smoking status and recommended LDCT screening to ever-smoking CRC survivors aged 55–80 years. The participants were classified into three risk groups: risk group 1 (RG1) who met the NLST criteria (Age 55–74 years, ≥ 30 pack-years of smoking, smoking cessation < 15 years); risk group 2 (RG2) who would not meet the NLST criteria but were at increased 6-year risk of lung cancer (PLCOM2012 ≥ 0.0151); risk group 3 (RG3) who did not meet any of the criteria above. RESULTS: Among 176 ever-smoking CRC survivors, 173 (98.3%) were male, 32 (18.2%) were current-smoker, and median age was 66 years (range, 55–79 years). We found 38 positive findings (non-calcified nodule ≥ 4 mm), 8 clinically significant findings, 66 minor abnormalities, and 64 negative findings on LDCT. Positive findings were identified in 15 of 79 (19.0%) of RG1, in 9 of 36 (25%) of RG2, and in 14 of 61 (23.0%) of RG3. Second primary lung cancers were found in 2 patients of RG2, and in 1 patient of RG3. SMN was most frequently found in RG2 (11 of 36 patients, 30.6%), compared with RG1 (12.7%) or RG3 (9.8%) (P = 0.016). CONCLUSIONS: LDCT screening for lung cancer in Korean CRC survivors is feasible. Well-designed clinical trial for defining high risk patients for lung cancer among CRC survivors is needed.
Colorectal Neoplasms ; Early Detection of Cancer ; Humans ; Lung Neoplasms ; Lung ; Male ; Mass Screening ; Mortality ; Neoplasms, Second Primary ; Republic of Korea ; Seoul ; Smoke ; Smoking ; Smoking Cessation ; Survival Rate ; Survivors ; Thorax

BACKGROUND: The influence of family history (FH) on cancer recurrence and survival among patients with established colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association of FH with cancer recurrence, survival, and the incidence of colorectal adenomas in patients with CRC. METHODS: Consecutive patients with stage III CRC diagnosed between 2004 and 2009 and followed-up in Severance Hospital were retrospectively enrolled and followed until December 2014. Overall survival (OS) and disease-free survival (DFS) according to FH of CRC or colorectal neoplasm were evaluated using Cox proportional hazards regression and Kaplan–Meier curve. RESULTS: Among analyzed 979 patients, 69 (7.0%) was identified as having a FH of CRC in a first-degree relative. During a median follow-up of 9.6 years, mortality occurred in 14 of 69 patients (20.3%) with a FH of CRC and 348 of 910 patients (38.2%) without a FH. Compared with patients without a FH, a first-degree FH of CRC, first or second-degree FH of CRC, and first-degree FH of colorectal neoplasm (CRC or polyps) were associated with a significant reduction in the risk of overall mortality, with adjusted hazard ratios (HRs) of 0.52 (95% CI, 0.29–0.92), 0.51 (95% CI, 0.30–0.88), and 0.48 (95% CI, 0.28–0.82), respectively. However, DFS improvement was significant only when the definition of FH was FH of colorectal neoplasm (adjusted HR 0.57; 95% CI, 0.36–0.89). The incidence of adenoma and advanced adenoma was not different according to the FH. CONCLUSIONS: Among patients with stage III CRC receiving curative surgery, a FH of colorectal neoplasm was associated with a reduction in cancer recurrence and mortality. The larger scaled studies are needed.
Adenoma ; Colorectal Neoplasms ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Mortality ; Recurrence ; Retrospective Studies