Cancer Prevention

The correlation between IL-4 polymorphisms and colorectal cancer risk in a population in Northwest China Our aim was to investigate whether polymorphisms in the interleukin-4 (IL-4) gene are associated with the risk of colorectal cancer (CRC) in a Chinese Han population. Six single-nucleotide polymorphisms (SNPs) in the IL-4 were genotyped by Agena MassARRAY in 248 CRC patients and 463 healthy controls. The association of IL-4 polymorphisms with CRC risk was assessed by genetic models, linkage disequilibrium, and haplotype analyses. The results suggested that the CC genotype of rs2243250 confers a lower risk of CRC in the recessive model [odds ratio (OR) =  0.42, 95% confidence interval (CI): 0.19–0.92, P = 0.020]. Similarly, rs2227284 GG was associated with a reduced risk of CRC in the codominant (OR = 0.18, 95% CI: 0.04–0.82, P = 0.027) and recessive (OR = 0.19, 95% CI: 0.04–0.83, P = 0.008) models adjusted for age. Our findings suggested that rs2243250 and rs2227284 in IL-4 are associated significantly with reduced CRC risk, which may facilitate the identification of CRC patients in Chinese populations.

Exploring the potential carcinogenic role of arsenic in gallbladder cancer Gallbladder cancer (GBC) is an aggressive malignancy, associated with dismal outcomes. Although several risk factors including age, sex, and gallstones have been postulated, epidemiologic determinants of the disease remain largely uncovered. Moreover, the implication of environmental toxicants as possible risk factors is increasingly suspected. Arsenic (As), an established human carcinogen, is a natural contaminant of groundwater and has a geographic distribution similar to GBC incidence. This, combined with As metabolites being partially excreted in bile, raised the hypothesis that As may represent a carcinogenic hazard for the gallbladder. We conducted an analysis of the association between As concentration in groundwater and incidence rates of GBC worldwide in 52 countries. The USA, India, and Taiwan were selected on the basis of availability and quality of data for further investigation at a county-level. Relationships between As levels and GBC incidence were assessed using multivariable linear regression analyses. Analyses revealed significant associations between high As concentrations in groundwater and increased GBC incidences. Among women, correlations were observed worldwide (Spearman = 0.31, P = 0.028), in Taiwan (Spearman = 0.57, P = 0.005) and in India (R2 = 0.23, P = 0.006). In men, a correlation was observed in India (R2 = 0.26, P = 0.009) and a modest correlation was identified in the USA (Spearman = 0.14, P = 0.026). These results provide some support to the hypothesis of an association between high exposures to As-contaminated water on GBC, which appeared more prominent in women. Further observational and molecular studies, conducted at the individual level, are required to confirm this association and decipher its nature.

Fluid intake and clinicopathological characteristics of bladder cancer: the West Midlands Bladder Cancer Prognosis Programme Objective Between 10 and 20% of bladder cancer patients who are diagnosed with nonmuscle-invasive bladder cancer will progress to muscle-invasive disease. Risk of progression depends on several factors at diagnosis including age, tumour stage, grade, size and number, and the presence or absence of carcinoma in situ. Fluid intake may be related to these factors. Methods Data of 1123 participants from the West Midlands Bladder Cancer Prognosis Programme were used. Data collection was via a semistructured questionnaire, and case report forms were used to collect clinicopathological data. Fluid intake was measured for six main categories: alcoholic fluids, hot fluids, fruit fluids, milk, fizzy drinks, and water, and converted into quintile variables. Multilevel mixed-effects linear regression was performed for every beverage category per clinicopathological variable and corrected for age, gender, and smoking status. Results Age at diagnosis was distributed differently amongst those in different total fluid intake quintiles (predicted means 71.5, 70.9, 71.5, 69.9, and 67.4, respectively) and showed a significant inverse linear trend in alcohol (P < 0.01), hot fluids (P < 0.01), and total fluids intake (P < 0.01), in nonmuscle-invasive bladder cancer patients. Conclusion Our results suggest an inverse association for alcohol intake and total fluid intake with age at diagnosis. These results should be confirmed by future studies, alongside a possible (biological) mechanism that could influence tumour growth, and the effect of micturition frequency.

Do socioeconomic factors play a role in nonadherence to follow-up colonoscopy after a positive faecal immunochemical test in the Flemish colorectal cancer screening programme? Objective In Flanders (Belgium), a population-based colorectal cancer (CRC) screening programme was started in 2013, coordinated by the Centre for Cancer Detection (CCD) in cooperation with the Belgian Cancer Registry (BCR). The CCD offers a biennial faecal immunochemical test (FIT) to Flemish citizens aged 56–74 years and recommends a colonoscopy when screened positive by FIT. The study objective is to investigate sociodemographic differences in follow-up colonoscopy adherence after a positive FIT. Methods Characteristics of the study population were derived by linkage of data from the CCD and BCR, linked with data of the Intermutualistic Agency and the Crossroads Bank for Social Security, resulting in aggregated tables to ensure anonymity. A total of 37 834 men and women aged 56–74 years with a positive FIT in 2013–2014 were included. Adherence to follow-up colonoscopy was calculated for age, sex, work intensity at household level, preferential reimbursement status, and first and current nationality. Descriptive analyses and logistic regressions were performed. Results Nonadherence to follow-up colonoscopy was associated with increasing age, and was significantly higher in men [odds ratio (OR), 1.08], participants with a preferential reimbursement status (OR, 1.34), very low work intensity (OR, 1.41), no payed work (OR, 1.38) and other than Belgian nationality by birth (OR, 1.6–4.66). Conclusion Adherence to follow-up colonoscopy after a positive FIT differs according to sociodemographic variables. Additional research is needed to explore reasons for nonadherence to colonoscopy and tackle barriers by exploring interventions to increase colonoscopy follow-up adherence after a positive FIT in the Flemish colorectal cancer screening programme.

Colorectal cancer risk factors in asymptomatic Chilean population: a survey of international collaboration between Japan and Chile In Chile, the mortality from colorectal cancer has been on the rise. A national screening program based on a fecal immunochemical test was started in 2012 as an international collaboration with Japan. This case-control study was designed to identify the risk factors for colorectal cancer, with a goal of increasing the participation rate for colorectal cancer screening. In accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, we conducted a case-control study from 2012 to 2017; 23 845 asymptomatic participants were enrolled in the study. Participants who were fecal immunochemical test-positive or had a family history of colorectal cancer underwent a colonoscopy. We analyzed the odds ratio of the risk factors for colorectal cancer, including sex, age, family history, BMI, hypertension, diabetes, regular use of nonsteroidal anti-inflammatory drugs, alcohol consumption, smoking, physical activity, and daily intake of certain food items. For the screening program, 202 cases of colorectal cancer were detected, and 195 of them were evaluated pathologically after resection. Of these, 173 cases (88.7%) had colorectal cancer stage 0/1, 151 (77.4%) of which were treated with endoscopic resection. In the multivariate analysis, male sex, family history of colorectal cancer, and low intake of cereals or fibers were closely related to a high colorectal cancer incidence. Moreover, participants in their 60s and 70s had a higher incidence of colorectal cancer than those in their 50s. These results suggest that intensive screening of the high-risk population can help in improving the detection of colorectal cancer, whereas higher consumption of cereals or fibers can be effective in preventing its onset.

Is leisure time sitting associated with mortality rates among men diagnosed with localized prostate cancer? Objective Being physically active postdiagnosis has been associated with lower rates of prostate cancer progression and mortality, but studies investigating postdiagnostic time spent sitting are lacking. We aim to study the association between leisure time sitting after a prostate cancer diagnosis and overall and prostate cancer-specific mortality. Methods Data from 4595 men in Sweden, diagnosed with localized prostate cancer between 1997–2002 and followed-up until the end of 2012, were analyzed. Time spent sitting during leisure time postdiagnosis was categorized into <2, 2–3, 3–4, and >4 h/day. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) of postdiagnosis leisure time sitting and a joint variable of sitting time and exercise, and time to overall or prostate cancer-specific death. Results The results showed no significant associations between postdiagnostic leisure time sitting and overall or prostate cancer-specific mortality rates. When the joint effect of both sitting and exercise time was considered, borderline significantly lower mortality rates for overall and prostate cancer-specific mortality were seen among participants that sat the least and exercised the most compared to the reference category with participants sitting the most and exercising least (HR: 0.75; 95% CI: 0.56–1.00 and HR: 0.61; 95% CI: 0.36–1.05, respectively). Conclusions No significant association between leisure time sitting and mortality rates among men diagnosed with localized prostate cancer was seen. This study does not support an association between leisure time sitting per se; however, being physically active may have beneficial effects on survival among men diagnosed with localized prostate cancer.

Prevalence of positive screening test results and agreement between cytology and human papillomavirus testing in primary cervical cancer screening in North-Western Romania Using data from a pilot study conducted in North-Western Romania, we aimed to estimate the prevalence of abnormal cytology and positive high-risk human papillomavirus (hr-HPV) test results in an ethnically diverse screening population and to assess the agreement between cytology and hr-HPV testing to evaluate the feasibility of integrating the latter as a primary test in the national cervical cancer screening program. The cross-sectional pilot study included Roma women, other ethnic minorities, and women in rural remote areas. Samples were taken for liquid-based cytology and hr-HPV testing (Hybrid Capture 2 DNA test) by a mobile health unit. The prevalence of positive screening results and the agreement between cytology and hr-HPV testing were estimated by κ coefficient. A total of 1019 women were included in the study. The population prevalence of positive screening results was similar for both tests (12%). The prevalence of abnormal cytology increased with increasing age, whereas the prevalence of positive hr-HPV test showed a bimodal age pattern. Substantial differences in the prevalence of abnormal cytology were found by ethnicity, with highest prevalence in Romanian women (14%), followed by Roma women (6%) and women of other ethnicities (5%) (P = 0.002). Similar ethnic differences in the prevalence of positive hr-HPV test were not observed. The overall agreement of positive screening results between the two methods was fair (κ = 0.25; 95% confidence interval = 0.18–0.30, P < 0.001) and ranged from poor to substantial depending on the age group. The prevalence of abnormal cytology result was high and similar to the prevalence of positive hr-HPV test result, which could allow for the implementation of hr-HPV testing as a primary test in the cervical cancer screening program in Romania.

Human papillomavirus vaccination in immigrants and descendants of immigrants in Denmark Objective In Denmark, human papillomavirus (HPV) vaccination has been offered at age of 12 to girls born in 1996 and later. In this cohort study, we examined routine HPV vaccination uptake in immigrants and descendants from different countries and regions compared with native Danes, including the influence of socioeconomic characteristics and potential changes in uptake by birth cohort. Methods In nationwide registers, we identified all girls born in 1996–2003 (n = 260 251) and obtained information on country of origin, HPV vaccinations and parents’ income and employment. Vaccination was defined as receiving ≥1 dose within 2 years after eligibility for routine vaccination. Odds ratios (ORs) were estimated by logistic regression separately for birth cohorts 1996–2000 and 2001–2003. Results Uptake in immigrants and descendants varied by country and region of origin. Overall, immigrants had lower uptake than native Danes, in birth cohorts 1996–2000 [79% vs. 93%, OR = 0.31; 95% confidence interval (CI), 0.29–0.34] and 2001–2003 (63% vs. 73%, OR = 0.60; 95% CI, 0.54–0.66). Descendants had lower uptake than native Danes in cohorts 1996–2000 (89% vs. 93%, OR = 0.65; 95% CI, 0.60–0.68), but higher uptake in cohorts 2001–2003 (76% vs. 73%, OR = 1.15; 95% CI, 1.08–1.21). Most associations were attenuated, but not entirely explained, when adjusting for socioeconomic characteristics. Conclusion HPV vaccination uptake varied by country and region. Most immigrants had lower uptake than native Danes, and in most groups, this was not fully explained by socioeconomic differences. Patterns in descendants were mixed. Interventions to increase uptake should be tailored to specific groups of immigrants/descendants.

A roadmap for a comprehensive control of cervical cancer in Poland: integration of available solutions into current practice in primary and secondary prevention In Poland, cervical cancer incidence and mortality still remain considerably higher than in Western European countries or North America. Recent data indicate decreasing trends in women younger than 60 years and stable trends in older women. In this article, we identified obstacles in primary and secondary prevention of cervical cancer in Poland. We analysed local legislation, management structure and organization of cervical cancer prevention in Poland and reviewed solutions available and implemented in other European countries. The main weaknesses include: (i) very low coverage of organized screening; concurrent unregistered opportunistic screening with unknown coverage and high test consumption (ii) suboptimal quality assurance in organized screening and no external quality assurance in opportunistic screening (iii) very low coverage of human papillomavirus vaccination that is not centrally reimbursed (iv) absence of pilot evaluation of (a) interventions that may improve population coverage and (b) performance of new preventive strategies. The proposed solutions are multifaceted and involve: (i) legislative and organizational regulation of cervical cancer screening aimed at comprehensive registration of procedures, data access and quality assurance (ii) pilot testing and implementation of new ways to increase coverage of cervical cancer screening, in particular among older women (iii) pilot evaluation with possible introduction of human papillomavirus-based screening and (iv) inclusion of human papillomavirus vaccination into the reimbursed national immunization program.

Circular RNA Pleiotrophin promotes carcinogenesis in glioma via regulation of microRNA-122/SRY-box transcription factor 6 axis Background: Circular RNAs (circRNAs) are recently identified as gene regulators in mammals and play important roles in carcinogenesis of cancer. For example, circRNA_PTN has been recognized as a biomarker of human cancer and is overexpressed in glioma. The molecular function of circRNA_PTN and its downstream targets in glioma, however, remains elusive. Methods: Quantitative polymerase chain reaction analysis was used to measure the expression of circular RNA pleiotrophin (circ_PTN) and miR-122. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, propidium iodide and Annexin-V/propidium iodide assay were performed to determine cell proliferation and apoptosis of glioma cells. Circular RNA Interactome and TargetScan were used to predict the potential microRNA targeting of circ_PTN and the potential targets of miR-122, respectively. Luciferase activity assay was used to validate these interactions. Downstream molecular mechanisms, including SRY-box transcription factor 6 (SOX6), extracellular regulated protein kinases (ERK), Cyclin D1, B-cell lymphoma-2 (BCL-2) and BCL2 associated X, apoptosis regulator (BAX), were determined by western blot. Results: Circ_PTN was overexpressed in glioma cells, and its knockdown induced cell proliferation inhibition, cell cycle arrest and apoptosis in glioma cells. The target microRNA of circ_PTN was predicted to be miR-122, the expression of which was negatively correlated with circ_PTN in glioma cells. Moreover, SOX6 was predicted as a potential target of miR-122, and miR-122 overexpression decreased SOX6 expression. MiR-122 inhibitor reversed the tumor-suppressing effects of circ_PTN knockdown, while overexpression of SOX6 impaired the miR-122 overexpression-induced cell growth inhibition and apoptosis. In addition, mitogen activated kinase-like protein (MAPK)/ERK pathway was involved in circ_PTN/miR-122/SOX6 axis. Conclusions: Circ_PTN acted as a sponge of miR-122 and upregulated miR-122 target SOX6, thus promoting carcinogenesis of glioma cells.