Assessment of long-term survival of cancer patients using cancer registry data from eastern China: Period analysis is superior to traditional methods.

We aimed to provide a systematical evaluation of the performance of period analysis compared to traditional cohort and complete methods, using cancer registry data from Taizhou, eastern China. Overall, 5-year relative survival (RS) estimate was calculated using cohort analysis, complete analysis and period analysis, respectively; further analyses were stratified by sex, region, age at diagnosis and cancer sites. Deviation value (DV), defined as the deviation between the estimated 5-year RS obtained from each method and the observed actual survival, was calculated to evaluate the accuracy of each method. Overall, 5-year RS derived by period analysis were much closer to the observed actual survival (51.4%), compared to those by complete and cohort methods, with the estimates of 48.7% (DV: -2.7%), 43.2% (DV: -8.2%) and 36.3% (DV: -15.1%), respectively. Further stratifications by sex, age at diagnosis, region and cancer sites also supported period analysis provided more precise estimates, compared to complete and cohort methods. We found, for first time systematically using cancer registry data from eastern China, period analysis provided more up-to-date precise estimates of long-term survival for overall and stratifications by sex, age at diagnosis, region and cancer sites, compared to traditional cohort and complete methods. Nevertheless, further investigations using large cancer registry data across China are warranted for the widespread use of period analysis in China.

Plasma cell-free DNA chromosomal instability analysis by low-pass whole-genome sequencing to monitor breast cancer relapse.

BACKGROUND: Chromosomal instabilities (CIN) of plasma cell-free DNA (cfDNA) are common in breast cancer. We aimed to investigate the value of cfDNA CIN in monitoring the breast cancer relapse and additionally to compare it with the traditional biomarkers (CA15-3 and CEA). METHODS: Overall 62 recurrent breast cancer patients and 20 healthy controls were recruited. Low-pass whole-genome sequencing (LPWGS) was performed to detect cfDNA CIN. A CIN score was calculated. The performance of CA15-3, CEA, and CIN score in monitoring the recurrence was investigated with receiver operating characteristic (ROC) curve and the area under curve (AUC). Multivariable Cox proportional hazard model was established to analyze the correlations between copy number gain/loss and disease-free survival (DFS). RESULTS: cfDNA CIN achieved the positive rate of 77.6% [(95% confidence interval (CI) 73.4-95.3%)] among recurrent breast cancer patients, with an AUC value of 0.933, superior to CA15-3 (positive rate: 38.7%; AUC: 0.864) and CEA (positive rate: 41.93%; AUC: 0.878) (P < 0.01). The combination of cfDNA CIN with two biomarkers further increased the positive rate to 88.7% (95% confidence interval 77.5-95.0%). cfDNA CIN achieved better performance in patients with shorter DFS (≤ 41 months), with an AUC value of 0.975. CONCLUSIONS: cfDNA CIN yields a higher accuracy in monitoring breast cancer recurrence compared to traditional biomarkers (CA15-3 and CEA), especially for biomarker-negative patients. The combination of cfDNA CIN to traditional biomarkers further improved the detection rate of recurrence, which may provide a new method for monitoring the early relapse of breast cancer, though further investigations are warranted.

A novel SNP in promoter region of RP11-3N2.1 is associated with reduced risk of colorectal cancer.

Single-nucleotide polymorphisms (SNPs) in the promoter region of long intergenic non-coding RNAs (lincRNAs) could play a regulatory role in its expression level and then get involved in colorectal cancer (CRC). Thus, we conducted a two-stage case-control study to investigate the associations of Tag SNPs within the promoter region of selected lincRNAs from microarray data with risk of CRC. A total of 320 cases and 319 controls were recruited in the test set to explore the associations between 16 SNPs with no deviations from Hardy-Weinberg equilibrium (HWE) and risk of CRC. Furthermore, 501 cases and 538 controls were included as the validation set to confirm the significant associations. RP11-3N2.1 rs13230517 polymorphism was found to be negatively associated with CRC in both test set (AA vs. GG, OR = 0.68, 95% CI = 0.48-0.96) and validation set (AA vs. GG, OR = 0.76, 95% CI = 0.59-0.98). Pooled analysis showed that individuals with GA/AA genotypes had a significantly decreased risk of CRC when compared with those carrying GG genotype (OR = 0.74, 95% CI = 0.60-0.90) in the combined set. The crossover analysis revealed that rs13230517 GA/AA carriers had a decreased risk of CRC than GG carriers among non-drinkers in both test and combined set. However, no gene-environment multiplicative interactions were found on risk of CRC. Our findings suggest that rs13230517 polymorphism might participate in the pathogenesis of CRC and have the potential to be a biomarker for predicting the risk of CRC.

[Multiple risk factors prediction models for high risk population of colorectal cancer].

Colorectal cancer is caused by the interaction of genetic and environment factors. Domestic and foreign scholars have attempted to develop several colorectal cancer risk prediction models, in order to identity risk factors, to screen for high risk population and evaluate the risk of developing colorectal cancer, so as to provide personalized screening protocols for individuals with different risk, and eventually reduce the incidence and mortality rate of colorectal cancer. Currently, the common colorectal cancer risk prediction models were mainly developed based on case-control study and cohort study. Models developed in European and American regions and Asia (excluding China) only include common risk factors, while Chinese models also include hereditary factors on the bases of common risk factors. However, the development and verification of each model are mainly based on local population, whether it can be applied for other population need to be determined. This article reviews the development, validation and evaluation of the risk prediction models, in order to provide a basis for developing more precise risk prediction models for colorectal cancer.

[Methodology for survival assessment of cancer patients using population-based cancer registration data].

Evaluating and monitoring long-term survival of cancer patients and reporting the survival rate are routinely employed by cancer registries. Long-term survival rate is a necessary indicator in evaluating the effect of cancer therapy and cancer burden. Cohort method is a traditional approach for survival analysis, but it essentially reflects the survival expectations of patients diagnosed many years ago, therefore survival status of cancer patients was often disclosed with delay. Given the limitation of cohort method, period analysis and model-based period analysis are subsequently proposed and gradually applied in assessment of survival rates in recent years. Period analysis includes the patients of interest period, which reflects more up-to-date estimates of long-term survival of cancer patients. While model-based period analysis can use the existing data to calculate survival rates and to assess the trend, and predict survival rates in the future. Compared with cohort approach, period analysis and model-based period analysis are better in timeliness and precision in survival analysis. This article reviews the definition and theory, calculation and application of cohort method, period analysis and model-based period analysis, in order to provide a basis on up-to-date and precise assessment of survival rates of cancer patients.

Comparative Evaluation of Preliminary Screening Methods for Colorectal Cancer in a Mass Program.

BACKGROUND: The fecal immunochemical test (FIT) has been widely used in preliminary screening for colorectal cancer (CRC). The high-risk factor questionnaire (HRFQ) and quantitative risk-assessment method (QRAM) are recommended for estimating the risk of CRC qualitatively and quantitatively in China. AIM: We aimed to prospectively compare the diagnostic values of CRC preliminary screening methods to identify which method is preferable as a screening strategy. METHODS: Individuals aged 40-74 years old were enrolled in a mass CRC screening program from January 1, 2007 to December 31, 2014, in Jiashan County, Zhejiang Province, China. FIT of two stool specimens at 1-week intervals was performed by laboratory personnel and face-to-face interviews were conducted by trained investigators. Screening data in the program were linked to a CRC surveillance and registry system, and CRC cases reported in the system were regarded as true patients. RESULTS: A total of 96,043 subjects were included. The sensitivity and specificity of FIT for detecting CRC cases were 75.49% (95% CI 69.84-80.39) and 90.36% (95% CI 90.17-90.54), respectively. QRAM was more sensitive (p < 0.001) and less specific (p < 0.001) than HRFQ. The sensitivity and specificity of FIT along with HRFQ were 86.56% (95% CI 81.81-90.22) and 81.37% (95% CI 81.12-81.62), and those of FIT along with QRAM were 88.93% (95% CI 84.47-92.23) and 73.95% (95% CI 73.67-74.23). CONCLUSIONS: Our findings suggest that CRC preliminary screening with FIT and QRAM in parallel has high sensitivity and satisfactory specificity, and is a useful strategy in mass screening programs.

Using period analysis to timely assess and predict 5-year relative survival for colorectal cancer patients in Taizhou, eastern China.

INTRODUCTION: While timely assessment of long-term survival for patients with colorectal cancer (CRC) is essential for evaluation on early detection and screening programs of colorectal cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for CRC patients in eastern China. METHODS: Patients diagnosed with CRC during 2004-2018 and followed up until December 31, 2018 from four cancer registries with high-quality data from Taizhou, eastern China were included. Period analysis was used to calculate 5-year relative survival (RS) for overall and the stratification by sex, age at diagnosis and region. The projected 5-year RS of CRC patients during 2019-2023 was also assessed using a model-based period analysis. RESULTS: Overall 5-year RS for patients with CRC during 2014-2018 reached 78.8%, being 74.9% for men and 86.1% for women. 5-year RS declined along with aging, decreasing from 84.1% for age < 45 years to 48.9% for age > 74 years, while 5-year RS for urban area was higher compared to rural area (83.9% vs. 75.8%). Projected overall 5-year RS of CRC patients could reach 85.9% during the upcoming period 2019-2023. CONCLUSIONS: We provided, for first time in China using period analysis, most up-to-date 5-year RS for patients with CRC from Taizhou, eastern China and also found 5-year RS for CRC patients have improved greatly during 2004-2018.

Using Period Analysis to Timely Assess and Predict 5-Year Relative Survival for Liver Cancer Patients From Taizhou, Eastern China.

Introduction: While timely assessment of long-term survival for patients with liver cancer is essential for the evaluation of early detection and screening programs of liver cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for liver cancer patients in eastern China. Methods: Patients diagnosed with liver cancer during 2004-2018 from four cancer registries with high-quality data from Taizhou, eastern China, were included. The period analysis was used to calculate the 5-year relative survival (RS) for overall and the stratification by sex, age at diagnosis, and region. The projected 5-year RS of liver cancer patients during 2019-2023 was also assessed using a model-based period analysis. Results: The overall 5-year RS for patients with liver cancer during 2014-2018 reached 32.4%, being 29.3% for men and 36.1% for women. The 5-year RS declined along with aging, decreasing from 38.2% for age <45 years to 18.8% for age >74 years, while the 5-year RS for urban area was higher compared to rural area (36.8% vs. 29.3%). The projected overall 5-year RS of liver cancer patients could reach 41.4% during the upcoming period 2019-2023. Conclusions: We provided, for first time in China using the period analysis, the most up-to-date 5-year RS for patients with liver cancer from Taizhou, eastern China, and also found that the 5-year RS for liver cancer patients have improved greatly during 2004-2018, which has important implications for the timely evaluation of early detection and screening programs for patients with liver cancer in eastern China.

Use of period analysis to timely assess 5-year relative survival for breast cancer patients from Taizhou, Eastern China.

Objectives: While timely assessment of long-term survival for patients with breast cancer is essential for evaluation on early detection and screening programs, those data are extremely scant in China. We aimed to derive most up-to-date survival estimates and to predict future survival using the cancer registry data from Taizhou city, Eastern China. Methods: Patients diagnosed with breast cancer during 2004-2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Period analysis was used to calculate 5-year relative survival (RS) for the overall population and according to the stratification factors sex, age at diagnosis and geographic region. We further predict the upcoming 5-year RS during 2019-2023, using continuous data from three 5-year periods (2004-2008, 2009-2013 and 2014-2018) and a model-based period approach. Results: Overall 6159 patients diagnosed with breast cancer during 2004-2018 were enrolled. The 5-year RS for breast cancer in 2014-2018 reached 88.8%, while women were higher compared to men (90.5% versus 83.7%) and urban areas were higher compared to rural areas (91.9% versus 86.7%). Additionally, we found a clear gradient by age at diagnosis, ranging from 94.8% for age<45 years to 83.3% for age>74 years. Projected overall 5-year RS for the upcoming 2019-2023 could reach 91.5% (84.8% for men and 93.5% for women). Conclusions: We provided, for first time in China, using period analysis, most up-to-date 5-year RS (88.8%) for patients with breast cancer from Taizhou, Eastern China. We also demonstrate the 5-year RS has improved greatly over last 15 years, which has important implications for timely evaluation of early detection and screening programs.

Using Population-Based Cancer Registration Data and Period Analysis to Accurately Assess and Predict 5-Year Relative Survival for Lung Cancer Patients in Eastern China.

BACKGROUND: The assessment of long-term survival of lung cancer patients based on data from population-based caner registries, using period analysis, was scarce in China. We aimed to accurately assess the long-term survival of lung cancer patients, and to predict the long-term survival in the future, using cancer registry data from Taizhou City, eastern China. METHODS: Four cancer registries with high-quality data were selected. Patients diagnosed with lung cancer during 2004-2018 were included. The long-term survival was evaluated using period analysis, with further stratification by sex, age at diagnosis and region. Additionally, projected 5-year relative survival (RS) of lung cancer patients for 2019-2023 was evaluated, using model-based period analysis. RESULTS: The 5-year RS of lung cancer patients diagnosed during 2014-2018 was 40.2% (31.5% for men and 56.2% for women). A moderate age gradient was observed for the period estimate, with the estimate decreasing from 50.5 to 26.5% in the age group of 15-44 years and ≥75 years, respectively. The 5-year RS of urban area was higher than that of rural area (52.3% vs. 38.9%). The overall projected 5-year RS of lung cancer patients was 52.7% for 2019-2023, with estimate of 43.0 and 73.2% for men and women, respectively. A moderate age gradient was also observed for the projected estimate. Moreover, estimate reached nearly 50% for rural and urban areas. CONCLUSION: Period analysis tended to provide the up-to-date and precise survival estimates for lung cancer patients, which is worth further application, and provides important evidence for prevention and intervention of lung cancer.

Genome wide profiling of miRNAs relevant to the DNA damage response induced by hexavalent chromium exposure (DDR-related miRNAs in response to Cr (VI) exposure).

AIM: We aimed to explore the expression of miRNAs and their potential roles in the DNA damage response (DDR) induced by Cr (VI) exposure in human B lymphoblast cells (HMy2.CIR cells) and in a population of Cr (VI)-exposed humans. METHODS: Differentially expressed miRNAs were found by a combination of miRNA sequencing and RT-qPCR validation in HMy2.CIR cells treated with K2Cr2O7. Differentially expressed miRNAs related to DDR were selected for functional study. The expression levels of differential miRNAs were also investigated in chromate workers. RESULTS: A total of 214 differentially expressed miRNAs were identified by sequencing, and the expression of 5 miRNAs among 25 associated with DDR was found to be consistent between sequencing and validation studies.Functional studies showed that miR-148a-3p, miR-21-5p, and miR-424-3p might be related to Cr (VI)-induced cell apoptosis, and miR-221-3p might participate in Cr (VI)-induced DDR. We also found that the expression of miR-21-5p and miR-424-3p was upregulated in chromate workers. CONCLUSIONS: Cr (VI) exposure could significantly impact miRNAs expression in vitro and in chromate workers. Functional studies showed that miR-148a-3p, miR-21-5p and miR-221-3p might take a crucial role in the cellular DDR induced by Cr (VI) exposure.

Multi-Infection Patterns and Co-infection Preference of 27 Human Papillomavirus Types Among 137,943 Gynecological Outpatients Across China.

Background: The epidemiological feature of human papillomavirus (HPV) infection is distinctive in China. We aimed to investigate the multi-infection patterns and co-infection preference of 27 HPV types among gynecological outpatients across China. Methods: Overall 137,943 gynecological outpatients were recruited from eight tertiary hospitals located in seven regions of China, between July 1st, 2014 and December 31st, 2016. The overall, region-specific, age-specific and type-specific prevalence of HPV infection were calculated, respectively. The pattern of HPV infection was also evaluated. Furthermore, rate ratio was calculated to evaluate the co-infection preference of any two HPV genotypes. Results: The overall prevalence of 27 HPVs' [17 high-risk (hr)/10 low-risk (lr)] infection was 23.5%. The age-specific HPV prevalence showed a "U-shaped" pattern. The most prevalent hrHPV genotypes were 16, 52, and 58. Multiple infections were detected in 25.8% of the HPV-positive women, in which dual infection was more prevalent. HPV 16/18 were likely to co-infected with HPV 31 but unlikely with HPV 52/58, i.e., the co-infection of HPV 16 with HPV 31 was high (3.5-fold), but low for HPV 58 (1.8-fold), and 52 (1.2-fold), while the co-infection of HPV 18 with HPV 31 was high (4.3-fold), but low for HPV 52 (1.9-fold), and 58 (1.7-fold). Conclusions: We found age-specific prevalence of HPV infection showed a "U-shaped" pattern for high and low risk HPV, suggesting the importance of screening among younger women and the necessary of detection among older women. We found a novel co-infection preference of HPV 16/18 with 31, 52, and 58, suggesting a need of developing and marketing prophylactic HPV vaccines that protect against more genotypes in China.

WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling.

Esophageal cancer micro environment factor WNT2 was critical in cancer metastasis. However, very little is known about WNT2 receptors and their role in the malignant progression of ESCC. The clinical significance and underlying molecular mechanisms of FZD2, one of the receptors of WNT2, was further investigated in ESCC. We found that FZD2 expression was positively correlated with WNT2 levels in clinical ESCC specimens through database analysis. Upregulated FZD2 expression was detected in 69% (69/100) of the primary ESCC cases examined, and increased FZD2 expression was significantly correlated with poor prognosis (P < 0.05). Mechanistically, FZD2 induced the migration and invasion of ESCC cells by regulating the FZD2/STAT3 signaling. In vivo xenograft experiments further revealed the metastasis-promoting role of FZD2 in ESCC. Moreover, we found that the WNT2 ligand could stabilize and phosphorylate the FZD2 receptor by attenuating FZD2 ubiquitination, leading to the activation of STAT3 signaling and the initiation of ESCC cell metastasis. Collectively, our data revealed that a novel non-canonical WNT2/FZD2/STAT3 signaling axis is critical for ESCC progression. Strategies targeting this specific signaling axis might be developed to treat patients with ESCC.

Prognosis Prediction of Colorectal Cancer Using Gene Expression Profiles.

Background: Investigation on prognostic markers for colorectal cancer (CRC) deserves efforts, but data from China are scarce. This study aimed to build a prognostic algorithm using differentially expressed gene (DEG) profiles and to compare it with the TNM staging system in their predictive accuracy for CRC prognosis in Chinese patients. Methods: DEGs in six paired tumor and corresponding normal tissues were determined using RNA-Sequencing. Subsequently, matched tumor and normal tissues from 127 Chinese patients were assayed for further validation. Univariate and multivariate Cox regressions were used to identify informative DEGs. A predictive index (PI) was derived as a linear combination of the products of the DEGs and their Cox regression coefficients. The combined predictive accuracy of the DEGs-based PI and tumors' TNM stages was also examined by a logistic regression model including the two predictors. The predictive performance was evaluated with the area under the receiver operating characteristics (AUCs). Results: Out of 75 candidate DEGs, we identified 10 DEGs showing statistically significant associations with CRC survival. A PI based on these 10 DEGs (PI-10) predicted CRC survival probability more accurately than the TNM staging system [AUCs for 3-year survival probability 0.73 (95% confidence interval: 0.64, 0.81) vs. 0.68 (0.59, 0.76)] but comparable to a simplified PI (PI-5) using five DEGs (LOC646627, BEST4, KLF9, ATP6V1A, and DNMT3B). The predictive accuracy was improved further by combining PI-5 and the TNM staging system [AUC for 3-year survival probability: 0.72 (0.63, 0.80)]. Conclusion: Prognosis prediction based on informative DEGs might yield a higher predictive accuracy in CRC prognosis than the TNM staging system does.

Deleterious Mutations in DNA Repair Gene FANCC Exist in BRCA1/2-Negative Chinese Familial Breast and/or Ovarian Cancer Patients.

Introduction: FANCC is reported as a novel susceptibility gene for breast cancer, however, its mutation remains unclear in Chinese population. We aimed to identify the germline mutations of FANCC in high-risk breast cancer patients in China. Methods: 255 BRCA1/2-negative Chinese familial breast and/or ovarian cancer (FBOC) patients were recruited for FANCC germline mutations screen. For whom 90 patients were detected by PCR-sequencing assay, and another 165 patients were detected by a 98-gene panel sequencing assay. The 98-gene panel sequencing assay was also used to screen other possible gene mutations for the patients with FANCC mutations detected by PCR-sequencing assay. Two hundred and fifty sporadic breast cancer (SBC) patients and 248 female non-cancer controls (FNCCs) were recruited for the genotyping analysis. Immunohistochemistry (IHC) analysis was used to evaluate the FANCC expression in patients with FANCC mutation. Results: We found one rare FANCC deleterious mutation (c.339G>A, p.W113X, 0.4%) and two novel non-synonymous variants (c.51G>C, p.Q17H, 0.4% and c.758C>A, p.A253E, 0.4%) in FBOC patients, whereas none of above mutations was identified in SBC patients or FNCCs. We also found that one novel synonymous variant (c.903A>G, p.A301A) existed in one FBOC patient. Additionally, two non-synonymous SNPs rs201407189 (c.973G>A, p.A325T) and rs1800367 (c.1345G>A, p.V449M), and two synonymous SNPs rs55719336 (c.816C>T, p.I272I) and rs79722116 (c.1407G>A, p.T469T) were identified in FBOC patients. Conclusion: FANCC deleterious mutations exist in Chinese FBOC patients and investigations on the penetrance and spectrum of FANCC mutations need to be further conducted.

Epidemiology of gynecologic cancers in China.

Cancer has become a major disease burden across the globe. It was estimated that 4.29 million new incident cases and 2.81 million death cases of cancer would occur in 2015 in China, with the age-standardized incidence rate (ASIR) of 201.1 per 100,000 and age-standardized mortality rate (ASMR) of 126.9 per 100,000, respectively. For females, 2 of the top 10 most common types of cancer would be gynecologic cancers, with breast cancer being the most prevalent (268.6 thousand new incident cases) and cervical cancer being the 7th most common cancer (98.9 thousand new incident cases). The incidence and mortality of gynecologic cancers have been constantly increasing in China over last 2 decades, which become a major health concern for women. Survival rates of gynecologic cancers are generally not satisfactory and decrease along with advancing stage, though national data on survival are still not available. It is of great importance to overview on the epidemiology of gynecologic cancers, which may provide scientific clues for strategy-making of prevention and control, and eventually lowering the incidence and mortality rate as well as improving the survival rate in the future.

Diagnostic Value of Methylated Septin9 for Colorectal Cancer Detection.

BACKGROUND: Methylated Septin9 (mSEPT9) has been suggested as a reliable biomarker in colorectal cancer (CRC) detection. We aimed to determine the diagnostic value of mSEPT9 for CRC detection in Chinese patients. In addition, we compared the diagnostic efficacy of mSEPT9 to traditional screening method [fecal occult blood test (FOBT)] and two biomarkers [carcinoembryonic antigen (CEA) and carbohydrate antigen-199 (Ca-199)]. METHODS: Overall 248 subjects including 123 patients with CRC and 125 controls were included. Plasma and fecal samples were collected for CEA, Ca-199, mSEPT9, and FOBT tests. Sensitivity and specificity were calculated to evaluate the diagnostic efficacy of each method; receiver operating characteristic (ROC) curve was plotted for the assessment of diagnostic accuracy, and comparisons among FOBT, mSEPT9, and the combination were assessed through area under the ROC curve (AUC). RESULTS: mSEPT9 achieved overall sensitivity and specificity of 61.8% [95% confidence interval (CI): 53.0-69.9%] and 89.6% (83.0-93.8%), respectively, with an AUC value of 0.757 (95% CI: 0.701-0.807), superior to FOBT [sensitivity: 61.4% (50.9-70.9%); specificity: 70.3% (59.1-79.5%); AUC: 0.658 (0.578-0.723)], CEA [sensitivity: 35.0% (27.1-43.7%); specificity: 62.6% (53.8-70.7%); AUC: 0.485 (0.411-0.559)], and Ca-199 [sensitivity: 17.9% (12.1-25.6%); specificity: 55.7% (48.9-64.1%); AUC: 0.353 (0.283-0.423)]. The combination of mSEPT9 and FOBT further improved sensitivity and AUC value of 84.1% (75.1-90.3%) and 0.807 (0.752-0.863), respectively, while specificity was declined to 62.2% (50.8-72.4%). CONCLUSION: mSEPT9 demonstrated best diagnostic ability in CRC detection compared with FOBT, CEA, and Ca-199. The combination of mSEPT9 and FOBT further improved diagnostic sensitivity especially for early stage disease, which may provide a new approach for future CRC screening, though further investigations are warranted.

Sex disparities in cancer incidence in Jiashan County, China, 1995-2014.

PURPOSE: To describe the sex-specific incidence rates and the male-to-female incidence-rate ratios (IRRs) of different cancer types, and to explore the corresponding sex disparities in an area of Eastern China. METHODS: We used data from the Cancer Registry in Jiashan County, and calculated the sex-specific age-standardized (2010 China standard population) incidence rates and the male-to-female IRRs for different cancer types during the period 1995-2014. RESULTS: The age-standardized incidence rates of all cancers for the whole period 1995-2014 were 151.48 per 100,000 person-years for males and 83.75 per 100,000 person-years for females, and the corresponding male-to-female IRR was 1.81 (95% confidence interval: 1.77-1.85). Specifically, males presented higher incidences in most types of cancer with the exceptions of cancers of connective and other soft tissues, gallbladder (including extrahepatic bile ducts), and thyroid gland. In addition, the age-specific incidences of the ten most common cancers in males were higher than those in females in most age groups. CONCLUSIONS: Our results reveal a male predominance in incidence for a majority of cancers in Jiashan County, Eastern China. Possible explanations for these sex disparities in cancer incidence may include lifestyle factors, particularly smoking.

Association of a novel genetic variant in RP11-650L12.2 with risk of colorectal cancer in Han Chinese population.

BACKGROUND: This study aimed to investigate the associations of selected polymorphisms in RP11-650L12.2 with the risk of colorectal cancer (CRC) in a Chinese population. METHODS: A total of 821 CRC cases (test set: 320, validation set: 501) and 857 healthy controls (test set: 319, validation set: 538) were enrolled in this study. Demographic characteristics and lifestyle information were collected by a validated questionnaire. A sample of 5ml venous blood was collected from each subject for DNA isolation, and the selected polymorphisms (rs144182521, rs514743, rs76071148, rs149941240) were genotyped by MassArray technique. RESULTS: The rs149941240 polymorphism was significantly associated with the risk of CRC, with ORs of 1.50 (95% CI: 1.15-1.96) by co-dominant model and 1.45 (95% CI: 1.21-1.87) by dominant model in the test set, respectively. Correspondingly, the ORs were 1.48 (95% CI: 1.19-1.82) and 1.41 (95% CI: 1.15-1.73) in the validation set, respectively. The crossover analysis showed that non-smokers with the variant genotypes in rs149941240 had a significantly increased risk of CRC than those with wild genotype by dominant model in the validation set (OR 1.42, 95% CI 1.04-1.96). However, no gene-environment multiplicative interactions of rs149941240 with tobacco smoking were found on risk of CRC. CONCLUSIONS: Our findings suggest that rs149941240 polymorphism was associated with the risk of CRC, and might contribute to the susceptibility to CRC. The effects of this polymorphism should be validated in a larger sample and require further mechanistic investigations to determine the nature of its influence on CRC.