Search

Groundwater poisoning by heavy metals has caused serious health hazards in the exposed population globally. Manganese (Mn) poisoning causing human health hazards is very meagerly reported worldwide. The present research elucidates for the first time the catastrophic effect of manganese causing cancer in the Gangetic plains of Bihar (India). The blood samples of n = 1146 cancer patients were voluntarily obtained for the study, after their consent. Their household water samples were also collected for the study. All the samples were analysed for Mn contamination by Atomic Absorption Spectrophotometer. The study indicates high Mn contamination in the cancer patient blood samples with highest content as 6022 µg/L. Moreover, the cancer patient's household handpump water samples also contained elevated Mn contamination. The correlation coefficient study finds significant association between Mn contamination in blood of cancer patients and their handpump water. The carcinoma group of cancer patients mostly in Stage III & IV had significant Mn contamination in their blood (above WHO/BIS permissible limit). The geospatial study depicts Mn contamination in handpump water in the state of Bihar in correlation with cancer patient's blood samples. This novel finding is being reported in India for the first time, which correlates cancer with handpump drinking water. The long-term Mn exposure could be one of the causative agents for elevating cancer incidences. However, other confounding risk factors cannot be denied., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Context: Observational studies have shown conflicting results as to whether exposure to neonatal phototherapy is associated with increased rates of childhood cancer., Objective: To describe the rates of childhood neoplasms and cancer after neonatal phototherapy., Data Sources: The CENTRAL, PubMed, Scopus, and Web of Science databases., Study Selection: Observational studies regardless of design were included., Data Extraction: The data were extracted by one author and validated by another. The risk-of-bias assessment was performed using the ROBINS-E and Joanna Briggs Institute critical appraisal tools., Results: Six cohort and 10 case-control studies were included. The overall risk of bias was high in seven and low in nine studies. In cohort studies, the odds ratio (OR) was increased for hematopoietic cancer (1.44; confidence interval [CI]: 1.16-1.80) and solid tumors (OR: 1.18; CI: 1.00-1.40). In case-control studies, the OR was 1.63 (CI: 0.99-2.67) for hematopoietic cancers and 1.18 (CI: 1.04-1.34) for solid tumors., Conclusions: Children with a history of neonatal phototherapy had increased risk of hematopoietic cancer and solid tumors. The evidence quality was limited due to the high risk of bias and potential residual confounding., Impact Statement: Exposure to neonatal phototherapy increased later risk of hematopoietic cancer and solid tumors. This is the most comprehensive study on the association between phototherapy and cancer, but the evidence quality was limited due risk of bias and residual confounding. Future large scale well conducted studies are still needed to better estimate the association and., (© 2024. The Author(s).)

While selenium is a cofactor of several antioxidant enzymes against cancer and is essential for human health, its excess intake may also be harmful. Though a safe intake of selenium has recently been recommended, it is not well understood in the Asian population. We aimed to determine the association between dietary intake of selenium and cancer risk in a case-control study of 3758 incident cancer cases (i.e., stomach, colon, rectum, lung cancers, and other sites) and 2929 control subjects in Vietnam. Daily intake of selenium was derived from a semiquantitative food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between selenium intake and cancer risk. We observed a U-shaped association between selenium intake and cancer risk. A safe intake ranged from 110.8 to 124.4 µg/day (mean 117.8 µg/day). Compared to individuals with the safe intake of selenium, individuals with the lowest intake (i.e., 27.8-77.2 µg/day) were associated with an increased risk of cancer (OR = 3.78, 95% CI 2.89-4.95) and those with the highest intake (169.1-331.7 µg/day) also had an increased cancer risk (OR = 1.86, 95% CI 1.45-2.39). A U-shaped pattern of association between selenium intake and cancer risk was stronger among participants with body mass index (BMI) < 23 kg/m 2 and never smokers than BMI ≥ 23 kg/m 2 and ever smokers (P's heterogeneity  = 0.003 and 0.021, respectively) but found in both never and ever-drinkers of alcohol (P heterogeneity  = 0.001). A U-shaped association between selenium intake and cancer risk was seen in cancer sites of the stomach, colon, rectum, and lung cancers. In summary, we found a U-shaped association between selenium intake and cancer risk and a safe selenium intake (mean: 117.8 µg/day) in the Vietnamese population. Further mechanistic investigation is warranted to understand better a U-shaped association between selenium intake and cancer risk., (© 2024. The Author(s).)

Post-transplantation cancer is a significant cause of mortality among kidney transplant recipients (KTR). The incidence of post-transplantation cancer varies based on geographic region and ethnicity. However, data on KTR from South East Asia, where characteristics differ from other parts of Asia, is lacking. We conducted a retrospective cohort study at a transplant center in Thailand to investigate the incidence of post-transplantation cancer and mortality rates. Factors associated with post-transplantation cancer and patient outcomes were analyzed using competing-risks regression. The study included 1156 KTR with a post-transplant follow-up duration of 5.1 (2.7-9.4) years. The age- and sex-adjusted incidence rate of post-transplant cancer was highest for urothelial cancer (6.9 per 1000 person-years), which also resulted in the highest standardized incidence ratio (SIR) of 42.5 when compared to the general population. Kidney cancer had the second-highest SIR of 24.4. Increasing age was the factor associated with an increased risk of post-transplant cancer (SHR 1.03; 95% CI 1.01-1.05). Human leukocyte antigen (HLA) DR mismatch was associated with a decreased risk of post-transplant cancer (SHR 0.72; 95% CI 0.52-0.98). Post-transplantation cancer was significantly associated with patient mortality (HR 3.16; 95% CI 2.21-4.52). Cancer significantly contributes to KTR mortality, and the risk profile for cancer development in Thai KTRs differs from that of Western and most Asian counterparts. Further research is essential to explore appropriate screening protocols for countries with high rates of urothelial and kidney cancer, including Thailand., (© 2024. The Author(s).)

Neoplasm is an umbrella term used to describe either benign or malignant conditions. The correlations between socioeconomic and environmental factors and the occurrence of new-onset of neoplasms have already been demonstrated in a body of research. Nevertheless, few studies have specifically dealt with the nature of relationship, significance of risk factors, and geographic variation of them, particularly in low- and middle-income communities. This study, thus, set out to (1) analyze spatiotemporal variations of the age-adjusted incidence rate (AAIR) of neoplasms in Iran throughout five time periods, (2) investigate relationships between a collection of environmental and socioeconomic indicators and the AAIR of neoplasms all over the country, and (3) evaluate geographical alterations in their relative importance. Our cross-sectional study design was based on county-level data from 2010 to 2020. AAIR of neoplasms data was acquired from the Institute for Health Metrics and Evaluation (IHME). HotSpot analyses and Anselin Local Moran's I indices were deployed to precisely identify AAIR of neoplasms high- and low-risk clusters. Multi-scale geographically weight regression (MGWR) analysis was worked out to evaluate the association between each explanatory variable and the AAIR of neoplasms. Utilizing random forests (RF), we also examined the relationships between environmental (e.g., UV index and PM 2.5 concentration) and socioeconomic (e.g., Gini coefficient and literacy rate) factors and AAIR of neoplasms. AAIR of neoplasms displayed a significant increasing trend over the study period. According to the MGWR, the only factor that significantly varied spatially and was associated with the AAIR of neoplasms in Iran was the UV index. A good accuracy RF model was confirmed for both training and testing data with correlation coefficients R 2 greater than 0.91 and 0.92, respectively. UV index and Gini coefficient ranked the highest variables in the prediction of AAIR of neoplasms, based on the relative influence of each variable. More research using machine learning approaches taking the advantages of considering all possible determinants is required to assess health strategies outcomes and properly formulate policy planning., (© 2024. The Author(s).)

Evidence on the relationship between legume consumption and risk of specific cancer sites is inconclusive. We used data from a series of case-controls studies, conducted in Italy and in the Swiss Canton of Vaud between 1991 and 2009 to quantify the association between legume consumption and several cancer sites including oral cavity, esophagus, larynx, stomach, colorectum, breast, endometrium, ovary, prostate and kidney. Multiple logistic regression models controlled for sex, age, education, smoking, alcohol, body mass index, physical activity, comorbidities, and consumption of fruit, vegetables, processed meat and total calorie intake were used to estimate the odds ratios (OR) for different cancer sites and their corresponding 95% confidence intervals(CI). For female hormone-related cancers, the models also included adjustments for age at menarche, menopausal status and parity. Although most of the estimates were below unity, suggesting a protective effect, only colorectal cancer showed a significant association. Compared to no consumption, the OR for consuming at least one portion of legumes was 0.79 (95% CI: 0.68-0.91), the OR for consuming two or more portions was 0.68 (95% CI: 0.57-0.82) and the estimate for an increment of one portion per week was 0.87 (95% CI: 0.81-0.93). The inverse association between legume consumption and colorectal cancer suggests a possible role of legumes in preventing cancer risk., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Cancer risk is associated with the widely debated measure body mass index (BMI). Fat mass and fat-free mass measurements from bioelectrical impedance may further clarify this association. The UK Biobank is a rare resource in which bioelectrical impedance and BMI data was collected on ~ 500,000 individuals. Using this dataset, a comprehensive analysis using regression, principal component and genome-wide genetic association, provided multiple levels of evidence that increasing whole body fat (WBFM) and fat-free mass (WBFFM) are both associated with increased post-menopausal breast cancer risk, and colorectal cancer risk in men. WBFM was inversely associated with prostate cancer. We also identified rs615029[T] and rs1485995[G] as associated in independent analyses with both PMBC (p = 1.56E-17 and 1.78E-11) and WBFFM (p = 2.88E-08 and 8.24E-12), highlighting splice variants of the intriguing long non-coding RNA CUPID1 (LINC01488) as a potential link between PMBC risk and fat-free mass., (© 2024. The Author(s).)

Individuals differ widely in their immune responses, with age, sex and genetic factors having major roles in this inherent variability 1-6 . However, the variables that drive such differences in cytokine secretion-a crucial component of the host response to immune challenges-remain poorly defined. Here we investigated 136 variables and identified smoking, cytomegalovirus latent infection and body mass index as major contributors to variability in cytokine response, with effects of comparable magnitudes with age, sex and genetics. We find that smoking influences both innate and adaptive immune responses. Notably, its effect on innate responses is quickly lost after smoking cessation and is specifically associated with plasma levels of CEACAM6, whereas its effect on adaptive responses persists long after individuals quit smoking and is associated with epigenetic memory. This is supported by the association of the past smoking effect on cytokine responses with DNA methylation at specific signal trans-activators and regulators of metabolism. Our findings identify three novel variables associated with cytokine secretion variability and reveal roles for smoking in the short- and long-term regulation of immune responses. These results have potential clinical implications for the risk of developing infections, cancers or autoimmune diseases., (© 2024. The Author(s).)

Dynamic interactions between organelles are responsible for a variety of intercellular functions, and the endoplasmic reticulum (ER)-mitochondrial axis is recognized as a representative interorganelle system. Several studies have confirmed that most proteins in the physically tethered sites between the ER and mitochondria, called mitochondria-associated ER membranes (MAMs), are vital for intracellular physiology. MAM proteins are involved in the regulation of calcium homeostasis, lipid metabolism, and mitochondrial dynamics and are associated with processes related to intracellular stress conditions, such as oxidative stress and unfolded protein responses. Accumulating evidence has shown that, owing to their extensive involvement in cellular homeostasis, alterations in the ER-mitochondrial axis are one of the etiological factors of tumors. An in-depth understanding of MAM proteins and their impact on cell physiology, particularly in cancers, may help elucidate their potential as diagnostic and therapeutic targets for cancers. For example, the modulation of MAM proteins is utilized not only to target diverse intracellular signaling pathways within cancer cells but also to increase the sensitivity of cancer cells to anticancer reagents and regulate immune cell activities. Therefore, the current review summarizes and discusses recent advances in research on the functional roles of MAM proteins and their characteristics in cancers from a diagnostic perspective. Additionally, this review provides insights into diverse therapeutic strategies that target MAM proteins in various cancer types., (© 2023. The Author(s).)

The inability to control cell proliferation results in the formation of tumors in many multicellular lineages. Nonetheless, little is known about the extent of conservation of the biological traits and ecological factors that promote or inhibit tumorigenesis across the metazoan tree. Particularly, changes in food availability have been linked to increased cancer incidence in humans, as an outcome of evolutionary mismatch. Here, we apply evolutionary oncology principles to test whether food availability, regardless of the multicellular lineage considered, has an impact on tumorigenesis. We used two phylogenetically unrelated model systems, the cnidarian Hydra oligactis and the fish Danio rerio, to investigate the impact of resource availability on tumor occurrence and progression. Individuals from healthy and tumor-prone lines were placed on four diets that differed in feeding frequency and quantity. For both models, frequent overfeeding favored tumor emergence, while lean diets appeared more protective. In terms of tumor progression, high food availability promoted it, whereas low resources controlled it, but without having a curative effect. We discuss our results in light of current ideas about the possible conservation of basic processes governing cancer in metazoans (including ancestral life history trade-offs at the cell level) and in the framework of evolutionary medicine., (© 2023. The Author(s).)

In recent years, indications for implanting mega-implants were established in managing major bone defects linked to revision arthroplasty due to loosening, periprosthetic fractures, re-implantation following periprosthetic joint infection, non-union following fractures as well as complex intraarticular primary fractures. This study was conducted to discuss and analyze the strategy of diagnosis and management of complications following the use of mega-implants in treating primary and periprosthetic fractures of the lower extremities. This is a monocentric retrospective study. Patients aged ≥ 18 years who underwent implantation of a megaendoprosthesis due to periprosthetic or primary fractures of the lower extremity between January 2010 and February 2023 were identified from the authors' hospital information system. We identified 96 patients with equal numbers of fractures (71 periprosthetic fractures and 25 primary fractures). 90 cases out of 96 were investigated in this study. The drop-out rate was 6.25% (six cases). The average follow-up period was 22 months (1 to 8 years) with a minimum follow-up of 1 year. The diagnosis of complications was provided on the basis of subjective symptoms, clinical signs, radiological findings and laboratory investigations such as C-reactive protein, leucocyte count and the microbiological findings. The indications for implantations of modular mega-implants of the lower extremities were periprosthetic fractures (65 cases/72.22%) and primary fractures (25 cases/27.78%). Pathological fractures due to malignancy were encountered in 23 cases (25.56%), in one case due to primary tumor (1.11%) and 22 cases due to metastatic lesions (24.44%). Two cases (2.22%) presented with primary intraarticular fractures with severe osteoporosis and primary arthrosis. In all cases with malignancy staging was performed. Regarding localization, proximal femur replacement was encountered in 60 cases (66.67%), followed by distal femur replacement (28 cases/31.11%) and total femur replacement (2 cases/2.22%). The overall complication rate was 23.33% (21 complications in 21 patients). The most common complication was dislocation which was encountered in nine cases (10%), all following proximal femoral replacement (9 cases out of 60, making 15% of cases with proximal femoral replacement). The second most common complication was infection (six cases, 6.67%), followed by four aseptic loosenings (4.44%), further intraoperative periprosthetic fracture in one case (1.11%) and a broken implant in one case (1.11%). We noticed no cases with wear and tear of the polyethylene components and no cases of disconnections of the modular components. Mega-endoprostheses enable versatile management options in the treatment of primary and periprosthetic fractures of the lower extremities. The rate of complications such as loosening, implant failure, dislocation and infection are within an acceptable range in this preliminary analysis. However, implantation of mega-endoprostheses must be strictly indicated due the limited salvage options following surgery., (© 2023. Springer Nature Limited.)

Cholesterol is an essential structural component of membranes that contributes to membrane integrity and fluidity. Cholesterol homeostasis plays a critical role in the maintenance of cellular activities. Recently, increasing evidence has indicated that cholesterol is a major determinant by modulating cell signaling events governing the hallmarks of cancer. Numerous studies have shown the functional significance of cholesterol metabolism in tumorigenesis, cancer progression and metastasis through its regulatory effects on the immune response, ferroptosis, autophagy, cell stemness, and the DNA damage response. Here, we summarize recent literature describing cholesterol metabolism in cancer cells, including the cholesterol metabolism pathways and the mutual regulatory mechanisms involved in cancer progression and cholesterol metabolism. We also discuss various drugs targeting cholesterol metabolism to suggest new strategies for cancer treatment., (© 2023. The Author(s).)

Combinations of lifestyle behaviors may lead to different cancer risks. This study aimed to identify the latent classes based on lifestyle behavior trajectories and to investigate the association between these latent classes and cancer risk. Participants in the 2002-2003 National Health Insurance Service general health examination were included. Data on smoking, alcohol drinking, body mass index (BMI), and physical activity measured four times between 2002 and 2009 were analyzed. Incident cancer cases were tracked from 2010 to 2018. Patterns of alcohol drinking, smoking, BMI, and physical activity and latent classes based on trajectories of smoking, alcohol drinking, BMI, and physical activity were identified. Among 2,735,110 adults (1,787,486 men and 947,624 women), 111,218 (69,089 men and 42,129 women) developed incident cancer. Six latent classes of lifestyle behavior were identified, with Class 1 (healthy class) involving only 0.2% of men and 0.5% of women. The highest risk class in males tended to be steady light drinkers and steady moderate smokers, have steady low frequency of physical activity, and be obese. This class showed a 1.47 times higher (95% CI = 1.29-1.69) risk of all cancers than did the healthy class. Among women, there was only an association between the highest risk class (tendency to be non-drinkers, light smokers) and colorectal cancer (HR = 1.70, 95% CI = 1.02-2.83). Only a small percentage of participants maintained a long-term healthy lifestyle. Identifying classes of behavior combinations and their links to cancer development is therefore critical for cancer prevention., (© 2023. Springer Nature Limited.)

Waterpipe smoking is an emerging epidemic and a severe public health problem worldwide. Observational studies on the hazards of a specific new waterpipe tobacco product are timely needed. The objectives were to analyze how dangerous waterpipe tobacco smoking is on the causes of all mortality, including cancer, and how effective smoking cessation is for improving health. We analyzed the hazards of exclusive waterpipe smoking through a prospective cohort study in Northern Vietnam. We obtained exposure data on the smoking status of specific cigarette and waterpipe and smoking cessation histories from each study participant. The outcome includes deaths due to all causes. The cause of death for each case is determined based on medical records. HR (95%CI) was estimated using a Cox proportional-hazards-regression analysis for overall mortality and all cancers. The ever-cigarette smoking group as the reference group, the exclusive waterpipe smoking group had a statistical increase in the risk for overall mortality HR (95% CI): 1.63 (1.32, 2.00), and all cancers HR (95%CI): 1.67 (1.18, 2.38). The risk of death increased statistically in the group of waterpipe smoking over 20 years for overall mortality HR (95%CI): 1.82 (1.45, 2.29), and all cancers HR (95%CI): 1.91 (1.27, 2.88). After stopping smoking, the risk of death decreased steadily. The risk of death was reduced by 41% for overall mortality HR (95%CI): 0.59 (0.39, 0.89), and 74% for death from cancers HR (95%CI): 0.26 (0.08, 0.83) after ten years or longer of cessation. Life expectancy was shortened by more than six years for the group of exclusive waterpipe smokers compared to non-smokers. This study found new novel hazards of exclusive waterpipe tobacco smoking. The findings are scientific evidence for developing strategies, policies, and budget allocations to control this novel tobacco product and promote cessation to improve life expectancy., (© 2023. The Author(s).)

Firefighters suffer an increased risk of cancer from exposures to chemicals released from fires. Our earlier research has found that fire toxicants not only remain on firefighters' PPE, but are also tracked back to fire stations. The UK Firefighter Contamination Survey assesses firefighters' risk of developing cancer due to occupational exposure to fire toxins. Over 4% of surveyed firefighters were found to have a cancer diagnosis, with the age-specific cancer rate up to 323% higher (35-39 year olds) than that of the general population. Firefighters who had served ≥ 15 years were 1.7 times more likely to develop cancer than those who had served less time. Firefighters were at least twice as likely to be diagnosed with cancer if they noticed soot in their nose/throat (odds ratio (OR) = 2.0, 1.1-3.5), or remained in their PPE for more than four hours after attending a fire incident (OR = 2.3, 1.1-5.2). Also associated with an increased likelihood of cancer was: eating while wearing PPE (OR = 1.8, 1.2-2.7); failing to store clean/dirty PPE separately (OR = 1.3, 1.0-1.7); working in a station that smells of fire (OR = 1.3, 1.0-1.8) or not having designated (separated) clean and dirty areas (OR = 1.4, 1.1-1.7); using an on-site washing machine to launder fire hoods (OR = 1.3, 1.0-1.7); feeling that cleaning is not taken seriously at work (OR = 1.5, 1.2-2.0)., (© 2023. The Author(s).)

This study aimed to evaluate the relative risk of malignancy in patients with Takayasu's arteritis compared to that in the general population. This retrospective nationwide cohort study used data from the Korean Health Insurance Review and Assessment Service database. All newly diagnosed patients with Takayasu's arteritis were identified between January 2009 and December 2019. They were observed until the diagnosis of malignancy, death, or end of the observational period, December 2020. The standardized incidence ratios (SIRs) of the overall and site-specific malignancies were estimated and compared with the incidence of cancer in the general population retrieved from the National Cancer Registry. We identified 1449 newly diagnosed patients with Takayasu's arteritis during the observational period (9196 person-years). A total of 74, 66, and 8 patients had overall, solid, and hematologic malignancies, respectively. The risks of overall [SIR, 1.62; 95% confidence interval (CI) 1.27-2.03], solid (SIR, 1.51; 95% CI 1.17-1.92), and hematologic (SIR, 4.05; 95% CI 1.75-7.98) malignancies were increased compared to those in the general population. In solid malignancies, breast (SIR, 2.07; 95% CI 1.16-3.42) and ovarian (SIR, 4.45; 95% CI 1.21-11.39) cancers had an increased risk. In hematologic malignancies, the risk of myelodysplasia increased (SIR, 18.02; 95% CI 3.72-52.66). Immunosuppressive agent use was not associated with malignancy. There was no specific period when cancer more frequently occurred. An increased risk of malignancy was observed in patients with Takayasu's arteritis compared to that in the general population in this large-scale nationwide population study of Korean health insurance data., (© 2022. The Author(s).)

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT), proposed to patients with high-risk myeloid malignancies, may ultimately fail because of disease relapse. Bone marrow (BM) CD34 + cells in Allo-HSCT recipients can be either re-emerging recipient malignant cells or donor cells attesting of hematopoietic reconstitution. In this context, investigating donor/recipient chimerism in the population of BM CD34 + sorted cells (BM-CD34 + SC) was performed in 261 Allo-HSCT recipients (matched n = 145, haploidentical n = 65, matched unrelated n = 51) with myeloid malignancies. BM-CD34 + SC chimerism was compared to that of whole peripheral blood (PB) cells as well as other Allo-HSCT-related parameters, and impact on relapse and survival was assessed. Thresholds of 98% donor cells for PB and 90% for BM-CD34 + SC were found to allow relapse prediction. This was completed by the application of machine learning tools to explore the predictive value of these parameters in multidimensional models with repeated iterations. BM-CD34 + SC mixed chimerism stood out with all these methods as the most robust predictor of relapse with a significant impact on disease-free and overall survivals even after haploidentical Allo-HSCT and/or PTCY administration. This marker therefore appears to be of great interest for the decision of preemptive treatment to avoid post-transplant relapse., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Due to recent increases in cancer burden worldwide, we investigated current awareness of cancer risk factors and the association between information sources and health behaviors for cancer prevention in Japan. A nationwide representative sample aged 20 years or older (563 men and 653 women) responded to a questionnaire as part of a population-based survey in December 2018. Tobacco smoking (55.7% of the mean attributable fraction of cancer risk overall) and cancer-causing infection (52.0%) were regarded more highly than other lifestyle factors as causes of cancer (obesity [36.6%], physical inactivity [31.9%], unbalanced diet [30.9%], and alcohol consumption [26.2%]). The association between information sources and health behaviors for cancer prevention was evaluated using a logistic regression model. The websites of public institutions, and health professionals were associated with a broad range of health behaviors including improving diet, exercise, cancer screening/health check-up, and abstinence from smoking/drinking. Among sources of print media, positive associations were observed between books and improving diet/exercise, brochures and cancer screening/health check-up, and advertisements and abstinence from smoking/drinking. A strategic health communication approach that utilizes various information sources and delivery channels is needed to inform the public about cancer prevention and to motivate risk-reducing behaviors in the population., (© 2022. The Author(s).)

Brukina is a millet based fermented milk product which is consumed as a beverage in Ghana. It is however prone to aflatoxin M 1 (AFM 1 ) contamination, which is a serious health challenge for low and middle-income countries in subtropical regions. This study aimed at evaluating AFM 1 levels and cancer risks associated with brukina (n = 150) sampled from different locations of the Greater Accra Region of Ghana. AFM 1 were measured with High-Performance Liquid Chromatography (HPLC) connected to a Fluorescence Detector (FLD).Cancer risk assessments were also conducted using models prescribed by the Joint FAO/WHO Expert Committee on Additives (JECFA). Out of the 150 samples analyzed for AFM 1 , 80/150 (53%) tested positive between the range 0.00 ± 0.001-3.14 ± 0.77 µg/kg. Cancer risk assessments of AFM 1 produced outcomes which ranged between 0.64 and 1.88 ng/kg bw/day, 0.31-9.40, 0.0323, and 1.94 × 10 -3 -0.06 for cases/100,000 person/yr for Estimated Daily Intake (EDI), Hazard Index (H.I), Average Potency, and Cancer Risks respectively for all age categories investigated. It was concluded that the consumption of brukina posed adverse health effects on the majority of the age categories in the different locations of Greater Accra Region since the calculated H.Is were greater than one (> 1). Therefore, contamination of brukina with AFM 1 should be considered a high priority in public health and Ghana's cancer risk management actions., (© 2022. The Author(s).)

Modest drinking has been repeatedly discussed in scientific papers as protective against certain diseases, such as cardiovascular diseases, but in most cases, alcohol worsens health conditions, especially when consumed at high risk levels. The complexity of the risk relationship between alcohol and health conditions has confused clinicians as to whether it should be recommended. The study aims to balance the risks and benefits of modest drinking. This retrospective cohort study of 430,016 adults recruited from a standard health-screening program since 1994, with 11,031 deaths identified as of 2008. Drinking distinguished "modest drinker" (no more than one drink a day) from "regular drinker". Mortality risks including all-cause mortality and diseases-specific mortality with hazard ratio (HR) were calculated by adjusting for 15 confounders. Life table was used for life expectancy. Risk predictors were subjected to Cox proportional hazards regression analysis to identify significant predictors in multivariate models and life expectancy analysis. Nearly one out of 4 males (23%) was a modest drinker, who gained 0.94 year (95% CI 0.65-1.23 year) in life over non-drinker and had 8% reduction in adjusted all-cause mortality (HR 0.92, 95% CI 0.86-0.97). In contrast, regular drinkers had 43% increase in overall mortality (HR 1.43, CI 1.35-1.52) and shortened life by 6.9 years (95% CI 6.6-7.1 years). As most drinkers also smoked, 59% in modest and 75% in regular, the combined effect shortened life by 2.0 years (95% CI 1.6-2.4 years) in modest drinker and 10.3 years (95% CI 9.8-10.7 years) in regular drinker. Cancer were increased in modest drinkers for oral (HR 2.35, CI 1.38-4.01) and esophageal (HR 3.83, CI 1.90-7.73) cancer. The gain of one year by modest drinkers was erased by a two to fourfold increase in oral and esophageal cancer and that drinking beyond modest amount led to a large loss of life expectancy. Given that drinkers are prone to cross the line of drinking, clinicians should balance the risks and benefits of drinking, as well as the understanding of whether the patient is at risk for addiction., (© 2022. The Author(s).)

In 2020, 45,364 HCT in 41,016 patients, 18,796 (41%) allogeneic and 26,568 (59%) autologous in 690 centers were reported. Changes observed were as follows: total number of HCT -6.5%, allogeneic HCT -5.1%, autologous HCT -7.5%, and were more pronounced in non-malignant disorders for allogeneic HCT and in autoimmune disease for autologous HCT. Main indications were myeloid malignancies 10,441 (25%), lymphoid malignancies 26,120 (64%) and non-malignant disorders 2532 (6%). A continued growth in CAR-T cellular therapies to 1874 (+65%) patients in 2020 was observed. In allogeneic HCT, the use of haploidentical donors increased while use of unrelated and sibling donors decreased. Cord blood HCT increased by 11.7% for the first time since 2012. There was a significant increase in the use of non-myeloablative but a drop in myeloablative conditioning and in use of marrow as stem cell source. We interpreted these changes as being due to the SARS-CoV-2 pandemic starting early in 2020 in Europe and provided additional data reflecting the varying impact of the pandemic across selected countries and larger cities. The transplant community confronted with the pandemic challenge, continued in providing patients access to treatment. This annual report of the EBMT reflects current activities useful for health care planning., (© 2022. The Author(s).)

Cutaneous immune-related adverse events are common in cancer patients receiving immunotherapies but seldom studied in a comprehensive way of collecting all cancer types with comparisons between different immune-oncology drugs and correlation to patient survival. In this retrospective cohort study, we recruited 468 cancer patients receiving immunotherapies in a tertiary referral center in Taiwan and try to determine real-world incidence of cutaneous immune-related adverse events and their associations with the survival rates. Among them, 128 patients (27.4%) had cutaneous immune-related adverse events, with maculopapular eruption (10.6%) and pruritus (10.1%) most frequently identified in the monotherapy group. The incidence of these cutaneous immune-related adverse events was highest in patients receiving pembrolizumab (34.1%, P < .0001). Concurrent usage of molecular-targeted therapy with immunotherapy was associated with a higher incidence (57.8%, P < .0001). The Kaplan-Meier plot and log-rank test showed that patients with any type of immune-related cutaneous adverse events had longer survival time than those without (P < .0001). In conclusion, having either type of cutaneous immune-related adverse event in cancer patients receiving immunotherapies was correlated with a longer overall survival. Prompt diagnosis and suitable treatment are important., (© 2022. The Author(s).)

To observe the safety and efficacy of CT-guided 3D template-assisted radioactive 125 I seed implantation in the treatment of unresectable advanced soft tissue sarcoma (STS). Sixty-two patients who underwent continuous 3D template-assisted radioactive 125 I seed implantation for the treatment of unresectable advanced STS from August 2017 to August 2018 were selected from four tumor treatment centers for retrospective analysis. The postoperative adverse reactions and tumor response were recorded, and the postoperative complications were observed and treated at the same time. The overall survival (OS) rate was determined. All patients successfully completed 125 I seed implantation. In practice, the median number of puncture needles used during the operation was 20, and the median number of 125 I particles was 88. There were no statistical differences in the relative dosimetry parameters before and after the operation (P > 0.05). Tumor evaluation was performed 6 months after the operation. The effective rate was 61.3%, and the local control rate was 93.5%. As of March 2020, the 1-year survival rate was 85.2%, and the 2-year survival rate was 49.0%. The OS was 23 months. CT-guided 3D template-assisted 125 I seed implantation for the treatment of unresectable STS has a high local control rate, thereby further prolonging the OS of patients with unresectable STS., (© 2022. The Author(s).)

Background/objectives: Poor diet quality has been associated with an increased risk of cancer. Here, we examine the association between dietary patterns derived with two methods, and combined and site-specific cancer incidence in Canada., Subjects/methods: Dietary data were obtained from participants enrolled in Alberta's Tomorrow Project, a prospective cohort study, between 2000 and 2008. Principle component analysis (PCA) and reduced rank regression (RRR) were used to derive dietary patterns, and data linkage with the Alberta Cancer Registry was used for incident cancer cases. Cox proportional hazard regressions were used to estimate multivariable-adjusted models for the association between each dietary pattern score with combined and site-specific cancer incidence., Results: PCA revealed three dietary patterns ("western", "prudent", and "sugar, fruits, and dairy") and RRR resulted in four patterns ("dietary fiber", "vitamin D", "fructose", and "discretionary fat"). Five cancer sites were included in our site-specific analysis: lung, colon, breast, prostate, and endometrial cancers. The most protective dietary patterns for combined cancer sites were the "Prudent" pattern (HR = 0.82, CI = 0.73-0.92) and the "Dietary fiber" pattern (HR = 0.82, CI = 0.69-0.97). The "Fructose" pattern was associated with increased risk of combined cancers (HR = 1.14, CI = 1.02-1.27). Three dietary patterns were protective against colon cancer ("Prudent", "Dietary fiber", and "Discretionary fats"), and other risk reductions were seen for the "sugar, fruit, and dairy" pattern (lung cancer), and the "Dietary fiber" pattern (prostate cancer)., Conclusions: These results support cancer prevention strategies for a diet high in vegetables, fruits, fish, and whole grains. Further studies should explore the possible association between discretionary fats and colon cancer., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The optimal CD34 + cell dose in the setting of RIC allo-HCT for myelofibrosis (MF) remains unknown. We retrospectively analyzed 657 patients with primary or secondary MF transplanted with use of peripheral blood (PB) stem cells after fludarabine/melphalan or fludarabine/busulfan RIC regimen. Median patient age was 58 (range, 22-76) years. Donors were HLA-identical sibling (MSD) or unrelated (UD). Median follow-up was 46 (2-194) months. Patients transplanted with higher doses of CD34 + cells (>7.0 × 10 6 /kg), had an increased chance of achievement of both neutrophil (hazard ratio (HR), 1.46; P < 0.001) and platelet engraftment (HR, 1.43; P < 0.001). In a model with interaction, for patients transplanted from a MSD, higher CD34 + dose was associated with improved overall survival (HR, 0.63; P = 0.04) and relapse-free survival (HR, 0.61; P = 0.02), lower risk of non-relapse mortality (HR, 0.57; P = 0.04) and higher rate of platelet engraftment. The combined effect of higher cell dose and UD was apparent only for higher neutrophil and platelet recovery rate. We did not document any detrimental effect of high CD34 + dose on transplant outcomes. More bulky splenomegaly was an adverse factor for survival, engraftment and NRM. Our analysis suggests a potential benefit for MF patients undergoing RIC PB-allo-HCT receiving more than 7.0 × 10 6 /kg CD34 + cells., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Environmental exposures and avoidable risk factors account for a large proportion of cancer burden. Exposures and lifestyle vary over time and between populations, which calls for updated and population-specific quantification of how various avoidable risk factors influence cancer risk to plan and design rational and targeted prevention initiatives. The study considered 12 risk-factor groups categorized as class I carcinogens by IARC/WCRF. Exposure data was derived from national studies and surveys and were linked to cancer incidence in 2018 based on the nationwide Danish Cancer Registry. In 2018, 23,078 men and 21,196 women were diagnosed with cancer excluding non-melanoma skin cancer, in Denmark. Of these, 14,235 (32.2%) were estimated to be attributable to avoidable class I carcinogens. Tobacco smoking accounted for 14.6% of total cancers, followed by UV-radiation that accounted for 5.8%. Based on exposure data from 2008, one-third of the cancers in Denmark in 2018 are estimated to be caused by class I carcinogens with tobacco use being the main contributor followed by UV-radiation. Our results should be integrated with public health policies to effectively increase awareness and promote strategies to decrease risk factor exposures at population level., (© 2022. The Author(s).)

Senescent cells in cancer tissue, including senescent fibroblasts and macrophages, have been reported to increase the malignant potency of cancer cells by secreting senescence-associated secretory phenotype (SASP). Otherwise, Senescence of tumor cells has been believed to inhibit tumor growth by halting the massive proliferation and increasing the chances of immune clearance. In particular, senescent tumor cells (STCs) have been thought that they rarely exist in carcinomas because oncogene-induced senescence needs to be overcome for protumorigenic cells to become malignant. However, recent studies have revealed that a considerable number of STCs are present in cancer tissue, even in metastatic sites. In fact, STCs are widely involved in cancer progression by leading to collective invasion and building a cytokine barrier to protect nonsenescent tumor cells from immune attack. Furthermore, therapy-induced STCs can induce tumor progression and recurrence by increasing stemness. However, obscure causative factors and their heterogeneity in various cancers make it difficult to establish the physiological role of STCs. Here, we summarize and review the current knowledge of the pathophysiology and role of STCs. We also outline the current status of therapeutic strategies for directly removing STCs or modulating the SASPs to maximize the positive functions of STCs while suppressing the negative functions., (© 2021. The Author(s).)

Exosomes play a vital role in cell-cell communication within the cancer microenvironment. Exosomal long noncoding RNAs (lncRNAs) are important regulators in cancer development and are involved in multiple processes, including cancer cell proliferation, angiogenesis, metastasis, drug resistance, and immunomodulation. Changes in the levels of exosomal lncRNAs often appear with the occurrence and development of cancer. Therefore, exosomal lncRNAs can be used as biomarkers for cancer diagnosis and prognosis. Exosomal lncRNAs can also indicate the treatment response of patients receiving chemotherapy. Moreover, exosomal lncRNAs are potential therapeutic targets for cancer treatment. In this review, we summarize the role of exosomal lncRNAs in cancer biology as well as in clinical management. A more comprehensive and in-depth understanding of the role of exosomal lncRNAs in cancer may help us better understand the mechanism of cancer development and clinically manage cancer patients., (© 2021. The Author(s).)

Circulating soluble programmed death-1 ligand (sPD-L1) is measurable in the serum of cancer patients. This study aimed to investigate the significance of sPD-L1 in cancer patients receiving immune checkpoint inhibitor therapy. Blood samples were obtained before and after immune checkpoint inhibitor therapy (January 2015 to January 2019). The study cohort consisted of 128 patients who were diagnosed with non-small cell lung cancer (n = 50), melanoma (n = 31), small cell lung cancer (n = 14), urothelial carcinoma (n = 13), and other cancers (n = 20). Patients with a high level (> 11.0 pg/μL) of sPD-L1 were more likely to exhibit progressive disease compared with those with a low level (41.8% versus 20.7%, p = 0.013). High sPD-L1 was also associated with worse prognosis; the median PFS was 2.9 (95% confidence interval [CI] 2.1-3.7) months versus 6.3 (95% CI 3.0-9.6) months (p = 0.023), and the median OS was 7.4 (95% CI 6.3-8.5) months versus 13.3 (95% CI 9.2-17.4) months (p = 0.005). In the multivariate analyses, high sPD-L1 was an independent prognostic factor for both decreased PFS (HR 1.928, p = 0.038) and OS (HR 1.788, p = 0.004). sPD-L1 levels did not correlate with tissue PD-L1 expression. However, sPD-L1 levels were positively correlated with neutrophil to lymphocyte ratios and negatively correlated with both the proportion and the total number of lymphocytes. We found that high pretreatment sPD-L1 levels were associated with progressive disease and were an independent prognostic factor predicting lower PFS and OS in these patients., (© 2021. The Author(s).)

Little is known about the comorbidities in actinic keratosis patients. To evaluate the association of actinic keratosis with certain malignancies. All patients with actinic keratosis (n = 61,438) and age- and sex-matched control subjects (n = 307,190) at a 5:1 ratio were enrolled using data from the Korean National Health Insurance Service between the years 2007 and 2014. In subjects with actinic keratosis, overall cancer incidence was higher than that for controls after income level, habitat, diabetes, hypertension, and dyslipidemia were adjusted (Hazard Ratio [HR] = 1.43 [95% confidence interval 1.38-1.47]). The positive association of specific cancers were observed in the following order: skin cancer (HR = 3.43 [2.47-4.75]), oral cavity and pharyngeal cancer (HR = 1.99 [1.57-2.52]), lymphoma (HR = 1.59 [1.28-1.96]), leukemia (HR = 1.35 [1.03-1.77]), prostate cancer (HR = 1.35 [1.21-1.51]), renal cancer (HR = 1.29 [1.02-1.63]), liver cancer (HR = 1.21 [1.09-1.35]), thyroid cancer (HR = 1.20 [1.05-1.38]), and gastric cancer (HR = 1.13 [1.03-1.23]). Although further research on pathologic mechanism is needed, the implications of a positive correlation between actinic keratosis and internal organ malignancies has great significance., (© 2021. The Author(s).)

Spermine oxidase (SMOX) catalyzes the oxidation of spermine to spermidine. Observational studies have reported SMOX as a source of reactive oxygen species associated with cancer, implying that inhibition of SMOX could be a target for chemoprevention. Here we test causality of SMOX levels with cancer risk using a Mendelian randomization analysis. We performed a GWAS of spermidine/spermine ratio to identify genetic variants associated with regulation of SMOX activity. Replication analysis was performed in two datasets of SMOX gene expression. We then did a Mendelian randomization analysis by testing the association between the SMOX genetic instrument and neuroblastoma, gastric, lung, breast, prostate, and colorectal cancers using GWAS summary statistics. GWAS of spermidine/spermine ratio identified SMOX locus (P = 1.34 × 10 -49 ) explaining 32% of the variance. The lead SNP rs1741315 was also associated with SMOX gene expression in newborns (P = 8.48 × 10 -28 ) and adults (P = 2.748 × 10 -8 ) explaining 37% and 6% of the variance, respectively. Genetically determined SMOX activity was not associated with neuroblastoma, gastric, lung, breast, prostate nor colorectal cancer (P > 0.05). A PheWAS of rs1741315 did not reveal any relevant associations. Common genetic variation in the SMOX gene was strongly associated with SMOX activity in newborns, and less strongly in adults. Genetic down-regulation of SMOX was not significantly associated with lower odds of neuroblastoma, gastric, lung, breast, prostate and colorectal cancer. These results may inform studies of SMOX inhibition as a target for chemoprevention., (© 2021. The Author(s).)

The inactivation of p53, a tumor suppressor, and the activation of the RAS oncogene are the most frequent genetic alterations in cancer. We have shown that a unique E. coli MazF-MazE toxin-antitoxin (TA) system can be used for selective and effective eradication of RAS-mutated cancer cells. This out of the box strategy holds great promise for effective cancer treatment and management. We provide proof of concept for a novel platform to selectively eradicate cancer cells using an adenoviral delivery system based on the adjusted natural bacterial system. We generated adenoviral vectors carrying the mazF toxin (pAdEasy-Py4-SV40mP-mCherry-MazF) and the antitoxin mazE (pAdEasy-RGC-SV40mP-MazE-IRES-GFP) under the regulation of RAS and p53, resp. The control vector carries the toxin without the RAS-responsive element (pAdEasy-ΔPy4-SV40mP-mCherry-MazF). In vitro, the mazF-mazE TA system (Py4-SV40mP-mCherry-MazF+RGC-SV40mP-MazE-IRES-GFP) induced massive, dose-dependent cell death, at 69% compared to 19% for the control vector, in a co-infected HCT116 cell line. In vivo, the system caused significant tumor growth inhibition of HCT116 (KRAS mut /p53 mut ) tumors at 73 and 65% compared to PBS and ΔPY4 control groups, resp. In addition, we demonstrate 65% tumor growth inhibition in HCT116 (KRAS mut /p53 wt ) cells, compared to the other two control groups, indicating a contribution of the antitoxin in blocking system leakage in WT RAS cells. These data provide evidence of the feasibility of using mutations in the p53 and RAS pathway to efficiently kill cancer cells. The platform, through its combination of the antitoxin (mazE) with the toxin (mazF), provides effective protection of normal cells from basal low activity or leakage of mazF., (© 2021. The Author(s).)

Angiogenesis is essential for the sustained growth of solid tumors. Hypoxia-inducible factor 1 (HIF-1) is a master regulator of angiogenesis and constitutive activation of HIF-1 is frequently observed in human cancers. Therefore, understanding the mechanisms governing the activation of HIF-1 is critical for successful therapeutic targeting of tumor angiogenesis. Herein, we establish a new regulatory mechanism responsible for the constitutive activation of HIF-1α in cancer, irrespective of oxygen tension. PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive transcription of HIF-1 target genes. Moreover, phosphorylation of the analogous site in HIF-2α (S435) stabilizes the protein through the same mechanism, indicating post-translational modification within the oxygen-dependent degradation domain as a mechanism of regulating the HIF-α subunits. In vitro and in vivo models demonstrate that expression of PIM1 is sufficient to stabilize HIF-1α and HIF-2α in normoxia and stimulate angiogenesis in a HIF-1-dependent manner. CRISPR mutants of HIF-1α (Thr455D) promoted increased tumor growth, proliferation, and angiogenesis. Moreover, HIF-1α-T455D xenograft tumors were refractory to the anti-angiogenic and cytotoxic effects of PIM inhibitors. These data identify a new signaling axis responsible for hypoxia-independent activation of HIF-1 and expand our understanding of the tumorigenic role of PIM1 in solid tumors., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

A prototypic pediatric cancer that frequently shows activation of RAS signaling is embryonal rhabdomyosarcoma (ERMS). ERMS also show aberrant Hedgehog (HH)/GLI signaling activity and can be driven by germline mutations in this pathway. We show, that in ERMS cell lines derived from sporadic tumors i.e. from tumors not caused by an inherited genetic variant, HH/GLI signaling plays a subordinate role, because oncogenic mutations in HRAS, KRAS, or NRAS (collectively named oncRAS) inhibit the main HH target GLI1 via the MEK/ERK-axis, but simultaneously increase proliferation and tumorigenicity. oncRAS also modulate expression of stem cell markers in an isoform- and context-dependent manner. In Hh-driven murine ERMS that are caused by a Patched mutation, oncHRAS and mainly oncKRAS accelerate tumor development, whereas oncNRAS induces a more differentiated phenotype. These features occur when the oncRAS mutations are induced at the ERMS precursor stage, but not when induced in already established tumors. Moreover, in contrast to what is seen in human cell lines, oncRAS mutations do not alter Hh signaling activity and marginally affect expression of stem cell markers. Together, all three oncRAS mutations seem to be advantageous for ERMS cell lines despite inhibition of HH signaling and isoform-specific modulation of stem cell markers. In contrast, oncRAS mutations do not inhibit Hh-signaling in Hh-driven ERMS. In this model, oncRAS mutations seem to be advantageous for specific ERMS populations that occur within a specific time window during ERMS development. In addition, this window may be different for individual oncRAS isoforms, at least in the mouse., (© 2021. The Author(s).)

The Apelin/APJ signalling pathway, involved in multiple physiological and pathological processes, has been attracting increasing interest recently. In our previous study, Apelin overexpression in colon26 tumor cells suppressed tumor growth by inducing vascular maturation. Here, we found that MC38 and LLC tumor growth were greater in the absence of Apelin than in wild-type (WT) mice, suggesting that Apelin acts as a tumor suppressor. Consistent with this, treating WT mice with [Pyr 1 ]Apelin-13 inhibited tumor growth. In MC38 tumors, only endothelial cells (ECs) strongly express APJ, a cognate receptor for Apelin, indicating that EC-derived Apelin might regulate tumor formation in an autocrine manner. Comparing with WT mice, larger numbers of vessels with narrower diameters were observed in tumors of Apelin knockout mice and lack of Apelin enhanced tumor hypoxia. Investigating immune cells in the tumor revealed that [Pyr 1 ]Apelin-13 infusion induced the accumulation of CD8 + and CD4 + T cells in central areas. Moreover, RNA-sequencing analysis showed that Apelin induces chemokine CCL8 expression in ECs. Thus, enhancing anti-tumor immunity might be one of the mechanisms by which Apelin is involved in tumor growth. Our result indicated that increased CCL8 expression might induce CD8  +  T cells infiltration into tumor and tumor inhibition.

Elevated plasma vitamin B12 has been associated with solid cancers, based on a single B12 measurement. We evaluated the incidence of solid cancers following B12 measurement in patients with persistent elevated B12, compared to patients without elevated B12 and to patients with non-persistent elevated B12. The study population included patients with at least two plasma B12 measurements without already known elevated-B12-related causes. Patients with elevated plasma B12 (≥ 1000 ng/L) at first measurement (n = 344) were matched for age and sex with patients having 2 normal B12 measurements (< 1000 ng/L) (NN group, n = 344). The patients with elevated plasma B12 at first measurement were split into 2 groups, according to the presence (EE group, n = 144) or the absence (EN group, n = 200) of persistent elevated plasma B12 at second measurement. We compared the cancer-free survival during 60 months between the groups after adjustment for the other elevated-B12-related causes in a survival competing risk model. Compared to the NN group, a persistent elevated plasma B12 ≥ 1000 ng/mL was strongly associated with the occurrence of solid cancer (HR 5.90 [95% CI 2.79-12.45], p < 0.001), contrary to non-persistent plasma B12 elevation (p = 0.29). These results could help to select patients in whom the screening for solid cancers would be of interest.

Serum levels of bilirubin, a strong antioxidant, may influence cancer risk. We aimed to assess the association between serum bilirubin levels and cancer risk. Data were retrieved from 10-year electronic medical records at Kyushu University Hospital (Japan) for patients aged 20 to 69 years old. The associations of baseline bilirubin levels with cancer risk (lung, colon, breast, prostate, and cervical) were evaluated using a gradient boosting decision tree (GBDT) model, a machine learning algorithm, and Cox proportional hazard regression model, adjusted for age, smoking, body mass index, and diabetes. The number of study subjects was 29,080. Median follow-up time was 4.7 years. GBDT models illustrated that baseline bilirubin levels were negatively and non-linearly associated with the risk of lung (men), colon, and cervical cancer. In contrast, a U-shaped association was observed for breast and prostate cancer. Cox hazard regression analyses confirmed that baseline bilirubin levels (< 1.2 mg/dL) were negatively associated with lung cancer risk in men (HR = 0.474, 95% CI 0.271-0.828, P = 0.009) and cervical cancer risk (HR = 0.365, 95% CI 0.136-0.977, P = 0.045). Additionally, low bilirubin levels (< 0.6 mg/dL) were associated with total death (HR = 1.744, 95% CI 1.369-2.222, P < 0.001). Serum bilirubin may have a beneficial effect on the risk of some types of cancers.

In a fishing community Thyborøn-Harboøre on the Danish West coast, a chemical factory polluted air, sea, and ground with > 100 xenobiotic compounds. We investigated cancer incidence in the community. A historical cohort was identified from the Central Population Register and followed for cancer incidence in the Danish Cancer Register including inhabitants from 1968-1970 at height of pollution, and newcomers in 1990-2006 after pollution control. Two fishing communities without pollution, Holmsland and Hanstholm, were referent cohorts. We calculated rate ratios (RR) and 95% confidence intervals (CI). In 1968-1970, 4914 persons lived in Thyborøn-Harboøre, and 9537 persons in Holmsland-Hanstholm. Thyborøn-Harboøre had a statistically significant excess cancer incidence compared with Holmsland-Hanstholm; RR 1.20 (95% CI 1.11-1.29) deriving from kidney and bladder cancer; stomach and lung cancer in men, and colorectal cancer in women. In 1990-2006, 2933 persons came to live in Thyborøn-Harboøre. Their cancer incidence was the same as for newcomers to Holmsland-Hanstholm; RR 1.07 (95% CI 0.88-1.30). Persons in Thyborøn-Harboøre at height of chemical pollution had a cancer risk 20% above persons living in non-polluted fishing communities with a pattern unlikely to be attributable to life style. The study suggested that chemical pollution may have affected cancer risk.

Lanatoside C has a promising anti-tumor activity and is a potential candidate for radiosensitizers. In this study, we have investigated the therapeutic efficacy of the combination of 131 I-trastuzumab and lanatoside C for inhibition of human epidermal growth factor receptor 2 (HER2) positive tumor progression in NCI-N87 xenograft model. The combination treatment ( 131 I-trastuzumab and lanatoside C) showed highest cytotoxicity when compared to non-treated control or trastuzumab alone or 131 I alone or 131 I-trastuzumab alone in vitro. Biodistribution studies using 131 I-trastuzumab or combination of 131 I-trastuzumab and lanatoside C showed tumor uptake in BALB/c nude mice bearing HER2 positive NCI-N87 tumor xenograft model. The higher tumor uptake was observed in 131 I-trastuzumab (19.40 ± 0.04% ID/g) than in the combination of 131 I-trastuzumab and lanatoside C (14.02 ± 0.02% ID/g) at 24 h post-injection. Most importantly, an antitumor effect was observed in mice that received the combination of 131 I-trastuzumab and lanatoside C (p = 0.009) when compared to control. In addition, mice received lanatoside C alone (p = 0.085) or 131 I-trastuzumab alone (p = 0.160) did not significantly inhibit tumor progression compared with control. Taken together, our data suggest that combination of 131 I-trastuzumab and lanatoside C might be a potential synergistic treatment for radioimmunotherapy to control the HER2 positive tumor.

Repeated weight fluctuation has been proposed as a potential risk factor for increasing morbidity and mortality including cancer. We aimed to investigate the association between body weight variability (BWV) and all cancer and site-specific cancer incidence and the impact of smoking on these associations. A total of 1,759,848 cancer-free male subjects who had their weight measured at least 5 times from the National Health Insurance Service-Health Screening Cohort from 2002 to 2011 were included and followed up until 2015. BWV was defined as the average absolute difference between successive values (ASV). The risk of cancer and site-specific cancer from BWV was identified using Cox proportional hazards regression analysis using hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders including weight, and stratified analysis was also conducted according to smoking status. During the 7,015,413 person-years of follow-up, 11,494 patients (0.65%) developed new-onset cancers. BWV was associated with a higher risk of all cancers after adjustment for confounders. The highest BWV quintile group compared to the lowest had greater risks of all cancers and site-specific cancers including lung, liver, and prostate cancer (HR 1.22, 95% CI 1.15-1.30; HR 1.22, 95% CI 1.07-1.39; HR 1.46, 95% CI 1.19-1.81; HR 1.36, 95% CI 1.15-1.62, in all cancers, lung, liver and prostate cancer, respectively). Due to small number of cancer occurrence, the risk of kidney cancer was increased, but statistically insignificant (HR 1.38, 95% CI 0.91-2.10). Similar results were observed in noncurrent smokers. However, in current smokers, the risks of all cancers and only prostate cancer were significantly increased in the highest BWV quintile group (HR 1.19, 95% CI 1.09-1.31; HR 1.51, 95% CI 1.08-2.11). The risk of kidney cancer also increased in this group, although the finding was not statistically significant (HR 1.77, 95% CI 0.87-3.63) This study suggested BWV is an independent risk factor for cancer in men, especially in lung, liver, and prostate cancer, but evidence was weaker in kidney cancer. This association remained significant only in prostate cancer in current smokers.

Background/objectives: The association of fermented soy products, separately from total soy products, with cardiovascular disease (CVD) and total cancer has not been reported. We examined this association in a population-based prospective cohort study in Japan., Subjects/methods: We studied 79,648 participants (42,788 women; 36,860 men) aged 45-74 years without a history of cancer, myocardial infarction, or stroke. Participants completed a food frequency questionnaire (1995-1998) and were followed to 2009-2012. Cox proportional hazards regression analysis was used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of incidence of CVD and total cancer according to quartiles of total soy products, nonfermented soy products, fermented soy products, miso soup, natto, total isoflavones from soy products, isoflavones from nonfermented soy products, and isoflavones from fermented soy products., Results: In women, we observed a significant inverse association between fermented soy product intake and the risk of CVD (multivariate HR in the highest compared with the lowest quartile of fermented soy product intake: 0.80; 95% CI: 0.68, 0.95; P for trend = 0.010), and also found significant inverse associations for natto and isoflavones among fermented soy products. In site-specific analysis, we observed a similar, significant inverse association between fermented soy product intake and the risk of stroke in women. We found no significant association between any soy product and risk of CVD in men or total cancer in both sexes., Conclusions: Intake of fermented soy products such as natto was inversely associated with the risk of CVD in women.

Green tea is commonly consumed in China, Japan, and Korea and certain parts of North Africa and is gaining popularity in other parts of the world. The aim of this review was to objectively evaluate the existing evidence related to green tea consumption and various health outcomes, especially cancer, cardiovascular disease and diabetes. This review captured evidence from meta-analyses as well as expert reports and recent individual studies. For certain individual cancer sites: endometrial, lung, oral and ovarian cancer, and non-Hodgkins lymphoma the majority of meta-analyses observed an inverse association with green tea. Mixed findings were observed for breast, esophageal, gastric, liver and a mostly null association for colorectal, pancreatic, and prostate cancer. No studies reported adverse effects from green tea related to cancer although consuming hot tea has been found to possibly increase the risk of esophageal cancer and concerns of hepatotoxity were raised as a result of high doses of green tea. The literature overall supports an inverse association between green tea and cardiovascular disease-related health outcomes. The evidence for diabetes-related health outcomes is less convincing, while the included meta-analyses generally suggested an inverse association between green tea and BMI-related and blood pressure outcomes. Fewer studies investigated the association between green tea and other health outcomes such as cognitive outcomes, dental health, injuries and respiratory disease. This review concludes that green tea consumption overall may be considered beneficial for human health.

Barcode beads allow efficient nucleic acid tagging in single cell genomics. Current barcode designs, however, are fabricated with a particular application in mind. Repurposing to novel targets, or altering to add additional targets as information is obtained is possible but the result is suboptimal. Here, we describe a modular framework that simplifies generation of multifunctional beads and allows their easy extension to new targets.

Over the years, interleukin (IL)-27 has received much attention because of its highly divergent, sometimes even opposing, functions in immunity. IL-30, the p28 subunit that forms IL-27 together with Ebi3 and is also known as IL-27p28 or IL-27A, has been considered a surrogate to represent IL-27. However, it was later discovered that IL-30 can form complexes with other protein subunits, potentially leading to overlapping or discrete functions. Furthermore, there is emerging evidence that IL-30 itself may perform immunomodulatory functions independent of Ebi3 or other binding partners and that IL-30 production is strongly associated with certain cancers in humans. In this review, we will discuss the biology of IL-30 and other IL-30-associated cytokines and their functions in inflammation and cancer.

Background/objectives: We evaluated the association between adherence to the 2013 Danish dietary guidelines and the risk of type 2 diabetes (T2D) in a Danish cohort., Subjects/methods: We used data from the Danish Diet, Cancer, and Health cohort. Participants aged 50-64 years were included from 1993-1997. Information on diet and covariates was collected at baseline using questionnaires and physical assessments. A diet index was developed to assess adherence to the Danish dietary guidelines. T2D cases were identified using the Danish National Diabetes Register. Cox proportional hazards regression was used to estimate hazard ratios (HR), and the pseudo-observation method was used to estimate risk differences, and 95% confidence intervals (CI)., Results: A total of 54,305 subject were included. During a median follow-up of 15 years, 7136 participants were diagnosed with T2D. After multivariable adjustment, the HR for high versus low adherence to the index was 0.57 (95 % CI: 0.48, 0.69) in men, and 0.71 (95% CI: 0.60, 0.83) in women. Compared with the lowest adherence to the index, high adherence was associated with a 6.58% (95% CI: -8.69; -4.47%) or 3.17% (95% CI: -4.90, -1.44%) lower risk of T2D in men and women, respectively., Conclusions: High adherence to the Danish food-based dietary guidelines was associated with lower risk of T2D in a Danish cohort, both on a relative and an absolute scale. Shifting from low to high adherence to the dietary guidelines may provide public health benefit.

Cancer immune evasion is one of the hallmarks of carcinogenesis. Cancer cells employ multiple mechanisms to avoid immune recognition and suppress antitumor immune responses. Recently, accumulating evidence has indicated that immune-related pathways are epigenetically dysregulated in cancer. Most importantly, the epigenetic footprint of immune-related pathways is associated with the patient outcome, underscoring the crucial need to understand this process. In this review, we summarize the current evidence for epigenetic regulation of immune-related pathways in cancer and describe bioinformatics tools, informative visualization techniques, and resources to help decipher the cancer epigenome.