Establishment of a multicomponent dietary bioactive human equivalent dose to delete damaged Lgr5+ stem cells using a mouse colon tumor initiation model Multicomponent therapy has gained interest for its potential to synergize and subsequently lower the effective dose of each constituent required to reduce colon cancer risk. We have previously showed that rapidly cycling Lgr5+ stem cells are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer risk. In the present study, we quantified the dose-dependent synergistic properties of dietary n-3 polyunsaturated fatty acids (PUFA) and curcumin (Cur) to promote targeted apoptotic deletion of damaged colonic Lgr5+ stem cells. For this purpose, both heterogeneous bulk colonocytes and Lgr5+ stem cells were isolated from Lgr5-EGFP-IRES-CreERT2 knock-in mice injected with azoxymethane (AOM). Isolated cells were analyzed for DNA damage (γH2AX), apoptosis (cleaved caspase-3), and targeted apoptosis (both γH2AX and cleaved caspase-3) at 12 h post-AOM injection. Comparison of the percentage of targeted apoptosis in Lgr5+ stem cells (GFPhigh) across a broad bioactive dose-range revealed an ED50 of 16.0 mg/day n-3 PUFA + 15.9 mg/day Cur. This corresponded to a human equivalent dose of 3.0 g n-3 PUFA + 3.0 g Cur. In summary, our results provide evidence that a low dose (n-3 PUFA + Cur) combination diet reduces AOM-induced DNA damage in Lgr5+ stem cells and enhances targeted apoptosis of DNA-damaged cells, implying that a lower human equivalent dose can be utilized in future human clinical trials.

Smoking and Helicobacter pylori infection: an individual participant pooled analysis (Stomach Cancer Pooling- StoP Project) Smoking has been associated with acquisition and increased persistence of Helicobacter pylori infection, as well as with lower effectiveness of its eradication. A greater prevalence of infection among smokers could contribute to the increased risk for gastric cancer. We aimed to estimate the association between smoking and seropositivity to H. pylori through an individual participant data pooled analysis using controls from 14 case–control studies participating in the Stomach Cancer Pooling Project. Summary odds ratios and prevalence ratios (PRs), adjusted for age, sex and social class, and the corresponding 95% confidence intervals (CIs) were estimated through random-effects meta-analysis. Heterogeneity was quantified using the I2 statistic and publication bias with Egger’s test. There was no significant association between smoking (ever vs. never) and H. pylori seropositivity (adjusted odds ratio = 1.08; 95% CI: 0.89–1.32; adjusted PR = 1.01; 95% CI: 0.98–1.05). The strength of the association did not increase with the intensity or duration of smoking; stratified analyses according to sex, age, region or type of sample did not yield a consistent pattern of variation or statistically significant results, except for participants younger than 55 years and who had been smoking for more than 30 years (adjusted PR = 1.08; 95% CI: 1.02–1.15). This is the first collaborative analysis providing pooled estimates for the association between smoking and H. pylori seropositivity, based on detailed and uniform information and adjusting for major covariates. The results do not support an association between smoking and H. pylori infection.

Gastric cancer: epidemiology, biology, and prevention: a mini review Gastric cancer is one of the most common causes of cancer-related mortality worldwide. The objective of this article is to review the epidemiology and biology of gastric cancer risk. This literature review explores the biological, clinical, and environmental factors that influence the rates of this disease and discuss the different intervention methods that may not only increase the awareness of gastric cancer but also increase screening in efforts to reduce the risk of gastric cancer. Helicobacter pylori infection is the primary risk factor for gastric cancer. Additional risk factors include geographical location, age, sex, smoking, socioeconomic status, dietary intake, and genetics. Primary and secondary prevention strategies such as dietary modifications and screenings are important measures for reducing the risk of gastric cancer. Interventions, such as H. pylori eradication through chemoprevention trials, have shown some potential as a preventative strategy. Although knowledge about gastric cancer risk has greatly increased, future research is warranted on the differentiation of gastric cancer epidemiology by subsite and exploring the interactions between H. pylori infection, genetics, and environmental factors. Better understanding of these relationships can help researchers determine the most effective intervention strategies for reducing the risk of this disease.

Colorectal cancer screening in hospitalized patients: results from the Nationwide Inpatient Sample Colorectal cancer (CRC) is preventable with regular screening. This study aims to determine estimates and predictors of inpatient CRC screening during hospitalization in the USA. This nationwide population-based study utilized data from the National Inpatient Sample database from 2005 to 2014 to examine rates of CRC screening among hospitalized patients. There were 6470 inpatient CRC screening nationwide from 129 645 394 inpatient hospitalizations. Multivariable analysis showed that higher rates of inpatient CRC screening were associated with: females compared to males [odds ratio (OR): 0.87; 95% confidence interval (CI): 0.78–0.97]; 50–59 years age group compared to 70–79 years (OR: 0.76; 95% CI: 0.62–0.94) and more than 80 years (OR: 0.47; 95% CI: 0.35–0.64); Charlson Comorbidity Index score of 0 compared to scores of 1–2 (OR: 0.79; 95% CI: 0.64–0.98), 3–4 (OR: 0.61; 95% CI: 0.49–0.76), more than 5 (OR: 0.61; 95% CI: 0.47–0.79); rural hospitals rather than urban teaching hospital (OR: 0.50; 95% CI: 0.39–0.63) and urban nonteaching hospitals (OR: 0.64; 95% CI: 0.49–0.82); hospitals in the Midwest region (OR: 1.56; 95% CI: 1.14–2.12) compared to the Northeast region; recent years of 2011/2012 (OR: 1.89; 95% CI: 1.44–2.49) and 2013/2014 (OR: 2.70; 95% CI: 2.14–3.41) compared to the period 2005/2006. The CRC screening rate among hospitalized patients admitted in US hospitals is low. There were no association of differences in racial, household income or health insurance status with inpatient CRC screening. Noninvasive screening methods in hospitalized patients like stool-based fecal immunochemical test provide a unique method of increasing cancer screening rates.

Cruciferous vegetable intake and colorectal cancer risk: Japan public health center-based prospective study We aimed to assess the association between cruciferous vegetable intake and colorectal cancer (CRC) development among Japanese adults aged between 45 and 74 years in the Japan Public Health Center-based Prospective Study. During 1 325 853 person-years of follow-up, 2612 CRC cases were identified. The association of cruciferous vegetable intake with CRC risk was assessed using a Cox proportional hazard regression model to compute hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders. No significant association was observed between the highest cruciferous vegetable intake quartile (compared with the lowest) and CRC risk in men (multivariate HRs: 1.08; 95% CI: 0.91, 1.29) and women (multivariate HRs: 0.99; 95% CI: 0.80, 1.22) and its subsites. Women showed a marginal negative association between cruciferous vegetable intake and the risk of colon cancer (CC) after excluding participants who developed CC in the first 3 years of follow-up (P for trend = 0.08); a positive association was found with proximal CC in men. Cruciferous vegetable intake does not have a significant association with CRC risk in the Japanese general population.

The effect of NSAIDs exposure on breast cancer risk in female patients with autoimmune diseases Both breast cancer and autoimmune diseases (ADs) are predominant in women. NSAIDs are common medications for AD. Evidence on the association between NSAIDs use and breast cancer risk is controversial. We investigated the association between NSAIDs exposure and breast cancer risk in female patients with AD. AD patients older than 18 years of age were enrolled from Taiwan Longitudinal Health Insurance Database 2005. The NSAID users were defined as AD patients who had ever taken NSAIDs for at least 3 months between 2000 and 2009. All individuals were followed from the date of first diagnosis of AD to the end of 2013 to evaluate the risk of breast cancer. We estimated the adjusted hazard ratio (HR) using Cox proportional hazard regression after adjusting for age, comorbidities and medications. A total of 12 331 NSAID users and 12 331 non-NSAID users were included in this study after 1: 1 individual matching. The NSAID users were less likely to develop breast cancer than the non-NSAID users (adjusted HR: 0.37; 95% confidence interval: 0.27–0.50; P < 0.001), even if they used NSAIDs with low cumulative defined daily doses (adjusted HR: 0.42; 95% confidence interval: 0.34–0.53; P < 0.001). The incidence of new-onset breast cancer in NSAID users was significantly decreased in users taking selective cyclooxygenase 2 inhibitors, diclofenac, ibuprofen and piroxicam. Lower cumulative hazard rates were found in the AD patients who used NSAIDs (P < 0.001). NSAID exposure is associated with a decreased risk of breast cancer in female AD patients.

Nomogram-based prediction of cervical dysplasia persistence/recurrence The widespread introduction of screening methods allow to identify cervical dysplasia before having invasive cancer. The risk of developing cervical dysplasia persistence/ recurrence following conization represent a major health issue. Although several studies tried to identify predictors for cervical dysplasia persistence/recurrence, no previous study has been conducted to develop a risk calculator. The current study aimed to identify predictors of cervical dysplasia persistence/recurrence among women undergoing primary conization. We aimed to build nomograms estimating the risk of developing cervical dysplasia recurrence. Data of consecutive women with diagnosis of high-risk human papillomavirus (HPV) undergoing conization were retrospectively evaluated (1503 patients). The risk of developing cervical dysplasia persistence/recurrence was assessed with Kaplan–Meier and Cox’s hazard models. Additionally, two nomograms were built to estimate likelihood of cervical dysplasia recurrence: the first based on baseline and operative parameters and the second focusing on type-specific HPV detected. The performance of the above nomograms was assessed using concordance index. A total of 1503 patients were analyzed. After a mean (SD) follow-up of 48.6 ( ± 17.5) months, 84 (5.6%) patients required secondary conization. By multivariate analysis, HIV infection [hazard ratio (HR): 7.78; 95% confidence interval (CI): 2.77–21.81; P < 0.001], positive margins (HR: 26.2; 95% CI: 14.1–48.71; P < 0.001) and persistence of HPV (HR: 6.82; 95% CI: 4.15–11.21; P < 0.001) correlated with cervical intraepithelial neoplasia 2+ persistence/recurrence. The importance of those variables was corroborated by our first nomogram. The second nomogram suggested the impact of type-specific HPV infection in predicting cervical dysplasia persistence/ recurrence. HPV16, HPV18, HPV33, HPV35 and HPV45 were the HPV types most commonly associated with cervical dysplasia persistence/recurrence. The concordance index was greater than 0.70 for both nomograms, thus suggesting the reproducibility of our models. We developed the first two nomograms predicting this risk. The findings of this study require external validation. Once validated our data might be useful to plan a tailored postoperative surveillance of women receiving primary conization.

Occupational and environmental exposure to polychlorinated biphenyls and risk of non-Hodgkin lymphoma: a systematic review and meta-analysis of epidemiology studies We carryied out a meta-analysis of studies on exposure to polychlorinated biphenyls (PCBs) and risk of non-Hodgkin lymphoma (NHL). Through a systematic search of the literature, we identified relative risks (RRs) for PCB exposure and NHL risk in 30 populations (10 occupational exposure, seven high environmental exposure, 13 without special exposure). We performed random effects meta-analyses for exposure to all PCBs, specific PCB congeners and risk of all NHL and NHL subtypes. The meta-RR for studies of occupational exposure, high environmental exposure, and no special exposure were 0.94 [95% confidence interval (CI): 0.84–1.03], 1.05 (95% CI: 0.94–1.16), and 1.03 (95% CI: 0.72–1.34), respectively, and the cumulative meta-RR was 0.96 (95% CI: 0.85–1.07). No positive associations were found for exposure to specific congeners, nor for NHL subtypes. The meta-RR for an increase of 100 ppb serum or fat PCB level was 1.02 (95% CI: 1.00–1.04). There was weak indication of publication bias. Our meta-analysis found no association between PCB exposure and NHL risk, in particular in studies of occupational exposures. We detected a weak dose-response relation; the possibility of residual confounding and other sources of bias cannot be ruled out. PCBs are not likely to cause NHL in humans.

Uptake of breast and cervical cancer screening in four Gulf Cooperation Council countries In Gulf Cooperation Council States, there is limited information on national levels of mammography and Pap smear screening uptake. The aim of this study is to provide a baseline for national estimates for mammography and Pap smear screening and to explore associations between screening uptake and socioeconomic factors. The nationally representative World Health Survey Plus, implemented in 2008/2009 in Kuwait, Oman, Saudi Arabia and United Arab Emirates (UAE), was used. Uptake of mammography and Pap smear was estimated for each country, followed by the examination of associations between screening and a range of socioeconomic variables. Levels of breast and cervical cancer screening uptake within recommended intervals in all countries were low. The percentages of women aged 40–75 years who had a mammogram were 4.9% in Saudi Arabia, 8.9% in Oman, 13.9% in the UAE and 14.6% in Kuwait. The percentages of women aged 25–49 years who had a Pap smear test were 7.6% in Saudi Arabia, 10.6% in Oman, 17.7% in Kuwait and 28.0% in the UAE. Marital status, wealth, education, nationality and place of residence are associated with screening uptake, with the lower educated, poor and unmarried having the lowest percentages of uptake. The four Gulf Cooperation Council countries need to set clear targets and increase the proportion of women who have regular breast and cervical cancer screening examinations. Health education campaigns and awareness programmes that are fully integrated into the health system are required to ensure women use services that are available to prevent breast and cervical cancers.

Reply to the letter from Beuy Joob and Viroj Wiwanitkit No abstract available