Geospatial Science for the Environmental Epidemiology of Cancer in the Exposome Era.

Geospatial science is the science of location or place that harnesses geospatial tools, such as geographic information systems (GIS), to understand the features of the environment according to their locations. Geospatial science has been transformative for cancer epidemiologic studies through enabling large-scale environmental exposure assessments. As the research paradigm for the exposome, or the totality of environmental exposures across the life course, continues to evolve, geospatial science will serve a critical role in determining optimal practices for how to measure the environment as part of the external exposome. The objectives of this article are to provide a summary of key concepts, present a conceptual framework that illustrates how geospatial science is applied to environmental epidemiology in practice and through the lens of the exposome, and discuss the following opportunities for advancing geospatial science in cancer epidemiologic research: enhancing spatial and temporal resolutions and extents for geospatial data; geospatial methodologies to measure climate change factors; approaches facilitating the use of patient addresses in epidemiologic studies; combining internal exposome data and geospatial exposure models of the external exposome to provide insights into biological pathways for environment-disease relationships; and incorporation of geospatial data into personalized cancer screening policies and clinical decision making.

Effects of Glutathione S-Transferases (GSTM1, GSTT1 and GSTP1) gene variants in combination with smoking or drinking on cancers: A meta-analysis.

BACKGROUND: This meta-analysis aimed to systematically summarize the association between cancer risks and glutathione s-transferases (GSTs) among smokers and drinkers. METHODS: Literature was searched through PubMed, Web of Science, CNKI, and WANFANG published from 2001 to 2022. Stata was used with fixed-effect model or random-effect model to calculate pooled odds ratios (ORs) and the 95% confidence interval (95% CI). Sensitivity and heterogeneity calculations were performed, and publication bias was analyzed by Begg and Egger's test. Regression analysis was performed on the correlated variables about heterogeneity, and the false-positive report probabilities (FPRP) and the Bayesian False Discovery Probability (BFDP) were calculated to assess the confidence of a statistically significant association. RESULTS: A total of 85 studies were eligible for GSTs and cancer with smoking status (19,604 cases and 23,710 controls), including 14 articles referring to drinking status (4409 cases and 5645 controls). GSTM1-null had significant associations with cancer risks (for smokers: OR = 1.347, 95% CI: 1.196-1.516, P < .001; for nonsmokers: OR = 1.423, 95% CI: 1.270-1.594, P < .001; for drinkers: OR = 1.748, 95% CI: 1.093-2.797, P = .02). GSTT1-null had significant associations with cancer risks (for smokers: OR = 1.356, 95% CI: 1.114-1.651, P = .002; for nonsmokers: OR = 1.103, 95% CI: 1.011-1.204, P = .028; for drinkers: OR = 1.423, 95% CI: 1.042-1.942, P = .026; for nondrinkers: OR = 1.458, 95% CI: 1.014-2.098, P = .042). Negative associations were found between GSTP1rs1695(AG + GG/AA) and cancer risks among nondrinkers (OR = 0.840, 95% CI: 0.711-0.985, P = .032). CONCLUSIONS: GSTM1-null and GSTT1-null might be related cancers in combination with smoking or drinking, and GSTP1rs1695 might be associated with cancers among drinkers.

Soy Product Consumption and the Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: The association between soy product consumption and cancer risk varies among studies. Therefore, this comprehensive meta-analysis of observational studies examines the association between soy product consumption and total cancer risk. METHODS: This study was conducted following the PRISMA guidelines. Up to October 2023, all eligible published studies were searched through PubMed and Web of Science databases. RESULTS: A total of 52 studies on soy product consumption were included in this meta-analysis (17 cohort studies and 35 case-control studies). High consumption of total soy products (RR: 0.69; 95% CI: 0.60, 0.80), tofu (RR: 0.78; 95% CI: 0.70, 0.86), and soymilk (RR: 0.75; 95% CI: 0.60, 0.93) were associated with reduced total cancer risk. No association was found between high consumption of fermented soy products (RR: 1.18; 95% CI: 0.95, 1.47), non-fermented soy products (RR: 0.95; 95% CI: 0.77, 1.18), soy paste (RR: 1.00; 95% CI: 0.88, 1.14), miso soup (RR: 0.99; 95% CI: 0.87, 1.12), or natto (RR: 0.96; 95% CI: 0.82, 1.11) and cancer risk. A 54 g per day increment of total soy products reduced cancer risk by 11%, a 61 g per day increment of tofu reduced cancer risk by 12%, and a 23 g per day increment of soymilk reduced cancer risk by 28%, while none of the other soy products were associated with cancer risk. CONCLUSION: Our findings suggest that high total soy product consumption, especially soymilk and tofu, is associated with lower cancer risk. More prospective cohort studies are still needed to confirm the causal relationship between soy product consumption and cancer risk.

Proportion of cancer cases and deaths attributable to potentially modifiable risk factors in Peru.

BACKGROUND: Limited evidence exists on the population attributable fraction (PAF) of cancer cases and deaths in Latin America. In Peru several studies have been published regarding the PAF of various risk factors and their associated diseases. The objective of this study was to estimate the fraction of cancer cases and deaths attributable to potentially modifiable risk factors in Peru in 2018, before the COVID-19 pandemic in the population of 15 years old and older. METHODS: An ecological study was conducted using the prevalence of exposure of the Peruvian population to modifiable risk factors for cancer, the relative risk associated with each factor, and the number of cancer cases and deaths in 2018 as inputs. We used the Parkin formula with a Montecarlo statistical simulation model to calculate the PAF and confidence intervals. The number of new cancer cases and deaths attributed to each risk factor was determined by multiplying the number of cases and deaths in each gender by the PAF of each risk factor. FINDINGS: In Peru, 38.5% of new cases (34.5% in men and 42% in women) and 43.4% of cancer-related deaths (43.4% in men and 43.4% in women) were attributable to modifiable risk factors. The number of cancers attributable was 25,308 (10,439 in men and 14,869 in women) and the number of deaths attributable to cancer was 14,839 (6,953 in men and 7,886 in women). The predominant modifiable risk factors contributing to the highest number of cases and deaths were HPV infection (4,563 cases, 2,409 deaths), current tobacco use (3,348 cases, 2,180 deaths), and helicobacter pylori infection (2,677 cases, 1,873 deaths). Among the risk factors, oncogenic infections constituted the group with the highest PAF (16.6% for cases, 19.2% for deaths) followed by other unhealthy lifestyle factors (14.2% for cases, 16.7% for deaths), tobacco (7.2% for cases, 7.2% for deaths) and ultraviolet radiation (0.5% for cases, 0.3% for deaths). CONCLUSIONS: Prior to the COVID-19 pandemic, 38.5% of cancer cases and 43.4% of cancer-related deaths in Peru were linked to modifiable risk factors in the population of 15 years old and older. Most preventable cancer cases and deaths were related to oncogenic infections, primarily caused by HPV and helicobacter pylori, followed by tobacco and obesity.

Long-term outcome of pediatric renal transplantation with donors younger than 6 years.

BACKGROUND: Renal transplantation is currently the best treatment option for patients with end-stage renal disease. However, the use of kidneys from donors under 6 years of age as a possibility to increase the organ pool in pediatric recipients remains a controversial matter. We aimed to investigate whether donor age is associated to the long-term functionality of the renal graft. Likewise, we analyzed the adaptation of the graft to the ascending functional requirements in the pediatric patient. METHODS: Retrospective study of the results obtained in pediatric recipients transplanted with grafts from donors between 3 and 6 years of age, comparing them with those of grafts from donors older than 6 years. Among the variables compared are cumulative graft survival, renal size, need for antiproteinuric therapy, GFR, incidence of rejection, pyelonephritis, renal failure and surgical or tumor complications. RESULTS: A total of 43 transplants were performed with donors aged 3-6 years, and 42 transplants with donors older than 6 years. Cumulative graft survival at 5 years was 81% for the younger donor group compared to 98% for the older donor group (p < .05). At 8 years, cumulative graft survival for donors <6 years was 74%. As for the mean estimated graft survival, it was 11.52 years for the younger donor group and 14.51 years for older donors. During follow-up, the younger donor group presented greater renal enlargement and need for antiproteinuric therapy. The older donors group had a higher GFR during the first year of follow-up, which then equalized in both groups. There were no statistically significant differences in the incidence of acute or chronic rejection, acute pyelonephritis, acute renal failure or surgical or tumor complications. CONCLUSIONS: Renal transplants of grafts equal to or less than 6 years old have good short-term and acceptable long-term results in pediatric patients.

Life Expectancy of Patients Undergoing Total Knee Arthroplasty: Comparison With General Population.

BACKGROUND: This study aimed to analyze the life expectancy and cause of death in osteoarthritis (OA) patients who underwent total knee arthroplasty (TKA) and to identify risk factors that affect long-term mortality rate after TKA. METHODS: Among 601 patients, who underwent primary TKA due to OA by a single surgeon from July 2005 to December 2011, we identified patients who died after the operation using data obtained from the National Statistical Office of Korea. We calculated 5-, 10-, and 15-year survival rates of the patients and age-specific standardized mortality ratios (SMRs) compared to general population of South Korea according to the causes of death. We also identified risk factors for death. RESULTS: The 5-year, 10-year, and 15-year survival rates were 94%, 84%, and 75%, respectively. The overall age-specific SMR of the TKA cohort was lower than that of the general population (0.69; P < 0.001). Cause-specific SMRs for circulatory diseases, neoplasms, and digestive diseases after TKA were significantly lower than those of the general population (0.65, 0.58, and 0.16, respectively; all P < 0.05). Male gender, older age, lower body mass index (BMI), anemia, and higher Charlson comorbidity index (CCI) were significant factors associated with higher mortality after TKA. CONCLUSION: TKA is a worthwhile surgery that can improve life expectancy, especially from diseases of the circulatory system, neoplasms, and digestive system, in patients with OA compared to the general population. However, careful follow-up is needed for patients with male gender, older age, lower BMI, anemia, and higher CCI, as these factors may increase long-term mortality risk after TKA. LEVEL OF EVIDENCE: III.

Breath of Danger: Unveiling PM2.5's Stealthy Impact on Cancer Risks.

This article explores the intricate relationship between airborne particulate matter (PM), specifically PM2.5, and its profound impact on human health, emphasising the heightened risks of cancer. Examining the composition and characteristics of PM2.5, such as particle size and surface area, reveals its ability to induce inflammatory injury and oxidative damage. The carcinogenic potential extends beyond respiratory implications, affecting various organs, including the digestive tract, breast, and prostate. In addition to the genotoxic effects of PM2.5, attached polycyclic aromatic hydrocarbons are recognized to be endocrine-disrupting chemicals with specific implications for breast and prostate cancer. Long-term exposure to PM2.5 is associated with increased cancer mortality, with specific risks identified for different cancer types. The linear correlation between cancer risk and PM2.5 concentration calls for a re-evaluation of permissible emission levels. The article concludes by proposing specific mitigating strategies for individuals exposed to elevated PM2.5. It suggests antioxidant-rich diets and supplements, and exploring inhalation-based antioxidant administration as potential protective measures.

New role of fat-free mass in cancer risk linked with genetic predisposition.

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.

[Cancer figures in Italy: an overview]. / Panoramica sui numeri del cancro in Italia.

BACKGROUND: the description of the geographical distribution and temporal trends of cancer is relevant for prevention and improving the quality of care. This is primarily achieved through the incidence measures derived from population cancer registries (CRs). In recent years, in Italy there has been a prevalence of 'real-time' estimates and projections, although based on rather dated data. Given the significant increase in registration activity and still in absence of a national cancer registry network, the recent publication of Volume 12 of Cancer Incidence in Five Continents (CI5) provides a valuable opportunity to update cancer incidence estimates in Italy and to provide national and macroarea reference estimates. OBJECTIVES: to explore the pattern of cancer in Italy by reviewing and reorganizing the most recent data from cancer registries. MATERIALS AND METHODS: data from Italian cancer registries included in CI5 for the years 2013-2017 were obtained. Populations were verified, corrected for errors, and normalized to Italian National census reconstruction. The completeness of CR data was assessed using the mortality/incidence ratio applied to potential outlier data. Age-specific rates, Age standardized rates (ASRs), and truncated rates for adults (35-64 years) were calculated for 79 different neoplasms. Analyses were performed for individual CRs and macroareas. Temporal comparisons were made for 23 CRs with data from 2008-2012. RESULTS: the observed incidence rates show extreme heterogeneity. Among males, the overall ASR ranges from 584 per 100,000 in the province of Reggio Calabria to 809.9 per 100,000 in the province of Sondrio. Among women, ASR is highest in Emilia-Romagna (540.5) and lowest in the province of Avellino (409.9). The gradient with decreasing rates from North to South is clearly visible only for female breast cancer. Higher rates of lung cancer are observed for the city of Naples in both genders. In adult males (35-64 years), ASRs of lung cancer are maximum in the provinces of Caserta and Naples, where they are more than double the ASRs observed in the Veneto Region. In general, a significant decline in male ASRs is observed in Northern Italy compared to the previous five-year period. A significant part of this trend is influenced by lung cancer that is significantly decreasing throughout the Centre-North among men and substantially increasing among women. The database and tables with details of all calculated indicators are provided as supplementary material. CONCLUSIONS: the analysis has shown the importance of a review of real CR data and, in general, working with real data to not only develop specific estimates of cancers in Italy, but also to share reference rates and basic data for further analysis. The present review has also revealed critical issues with data submitted to the IARC. The comparison and verification of data quality through control and audit processes must represent a concrete operational perspective of the national cancer registry network. From the perspective of cancer epidemiology, important indications emerge regarding the distribution of cancers that can fuel aetiological research, as well as the planning of prevention and care activities. The data also show that it is advisable to separate the provinces of Caserta and Naples from the South in estimation and projection models. The comparison and verification of data quality through control and audit processes must represent a concrete operational perspective of the national cancer registry network.

Environmental Pollution and Risk of Childhood Cancer: A Scoping Review of Evidence from the Last Decade.

The long-term effects of environmental pollution have been of concern as several pollutants are carcinogenic, potentially inducing a variety of cancers, including childhood cancer, which is a leading cause of death around the world and, thus, is a public health issue. The present scoping review aimed to update and summarize the available literature to detect specific environmental pollutants and their association with certain types of childhood cancer. Studies published from 2013 to 2023 regarding environmental pollution and childhood cancer were retrieved from the PubMed database. A total of 174 studies were eligible for this review and were analyzed. Our search strategy brought up most of the articles that evaluated air pollution (29%) and pesticides (28%). Indoor exposure to chemicals (11%), alcohol and tobacco use during pregnancy (16%), electromagnetic fields (12%), and radon (4%) were the subjects of less research. We found a particularly high percentage of positive associations between prenatal and postnatal exposure to indoor (84%) and outdoor (79%) air pollution, as well as to pesticides (82%), and childhood cancer. Positive associations were found between leukemia and pesticides and air pollution (33% and 27%); CNS tumors and neuroblastoma and pesticides (53% and 43%); and Wilms tumor and other rare cancers were found in association with air pollution (50%). Indoor air pollution was mostly reported in studies assessing several types of cancer (26%). Further studies are needed to investigate the mechanisms underlying the potential associations between indoor/outdoor air pollution and pesticide exposure with childhood cancer risk as more preventable measures could be taken.

Does the duration of diabetes increase the risk of cancer? A nationwide population-based cohort of patients with new-onset diabetes and a matched reference cohort.

Diabetes mellitus and cancer are both common health issues, but the correlation between these two diseases remains unclear. We investigated the association of cumulative exposure of diabetes mellitus as an indication of hyperglycemia in terms of disease duration on multiple cancer types. We hypothesized that the risk of cancer would increase over time after the onset of diabetes. The study population consisted of a population-based cohort of 398,708 people and it was constructed from the Finnish CARING project. The Diabetes group consisted of 185,258 individuals, and the non-diabetic reference group comprised 187,921 individuals. Over 4.1 million person-years were accumulated, and the median follow-up time was 10.55 years. In the diabetes group, 25,899 cancer cases were observed compared with 23,900 cancers in the non-diabetic group. We did not find a clear relationship between the duration of diabetes mellitus and most cancer types examined. However, for cancers of the pancreas, prostate gland, bronchus, and lungs, a temporal relationship was found. Furthermore, even within the cancer types where the relationship was detected, it did not change over time. These findings indicate that diabetes does not independently increase the risk of cancer. Instead, the development of diabetes may be attributed to shared risk factors with cancer, such as obesity and/or insulin resistance accompanied by hyperinsulinemia. Thus, it is likely that the clock for increased cancer risk starts ticking already before onset of diabetes and hyperglycemia.

Enterocolitis and other immunotherapy and targeted therapy-related gastrointestinal manifestations: A review for gastroenterologist.

New oncologic treatments, particularly immunotherapy (IT), have revolutionized the treatment of advanced-stage malignant tumors. Immune checkpoint inhibitors are the main form of IT and act by increasing T cell activity and the organism's immune response against neoplastic cells. Targeted therapy is another form of IT that acts by inhibiting oncogenes or inflammation signaling and tumor angiogenesis pathways. However, these mechanisms of tumor destruction can interfere with the host's immune self-tolerance or with the mechanisms of epithelial tissue repair and predispose to immune system-mediated adverse events that can affect multiple organs, including the digestive tract. The gastrointestinal manifestations of damage caused by IT can range from low-grade mucositis to ulceration, and in some cases, necrosis and perforation. Any part of the gastrointestinal tract can be affected, but there is greater involvement of the small bowel and colon, with a pattern similar to that seen in inflammatory bowel disease. The most common clinical manifestation is chronic diarrhea. The differential diagnosis includes enteropathogenic infections, especially those caused by opportunistic microorganisms; adverse drug reactions; and other inflammatory and malabsorption disorders. Treatment is guided by damage severity. Mild cases can be treated with antidiarrheals and rehydration in the outpatient setting; moderate cases with hospitalization, systemic steroids, and temporary suspension of IT; and severe cases with immunosuppressants or biologic agents and definitive suspension of IT.

Incidence of De Novo Post-Transplant Malignancies in Thai Adult Kidney Transplant Recipients: A Single-Center, Population-Controlled, Retrospective Cohort Study at the Highest Volume Kidney Transplant Center in Thailand.

Kidney transplant recipients (KTRs) are at increased risk of developing de novo post-transplant malignancies (PTMs), with regional differences in types with excess risk compared to the general population. A single-center, population-controlled, retrospective cohort study was conducted at a tertiary care center in Thailand among all adults who underwent their first kidney transplant from 1986 to 2018. Standardized incidence ratios (SIRs) of malignancy by age, sex, and place of residence were obtained using data from the National Cancer Registry of Thailand as population control. There were 2,024 KTRs [mean age, 42.4 years (SD 11.4); female patients, 38.6%] during 16,495 person-years at risk. Of these, 125 patients (6.2%) developed 133 de novo PTMs. The SIR for all PTMs was 3.85 (95% CI 3.22, 4.56), and for pooled solid and hematologic PTMs, it was 3.32 (95% CI 2.73, 3.99). Urothelial malignancies had the largest excess risk, especially in women [female SIR 114.7 (95% CI 66.8, 183.6); male SIR 17.5 (95% CI 8.72, 31.2)]. The next two most common cancers were non-Hodgkin's lymphoma and skin cancer [SIR 20.3 (95% CI 13.6, 29.1) and 24.7 (95% CI 15.3-37.8), respectively]. Future studies are needed to identify the risk factors and assess the need for systematic screening among PTMs with excess risk in KTRs.

Meta-Analysis of Incidence and Mortality of Firefighter Cancer: An Update on Emerging Science.

BACKGROUND: Firefighters are faced with a broad range of toxic exposures during their work, including known and suspected carcinogens. The current study is an update to the previously published meta-analysis of cancer risk among firefighters by Soteriades and colleagues, and focuses on studies published from 2008 to 2020. METHODS: A comprehensive search of the literature was conducted, including electronic databases and bibliographies of recently published papers. Analyses include stratification of studies conducted in the United States (US) versus other countries. Cancer incidence and mortality rates were compared to the relevant general population. Random effects models were used to calculate summary risk estimates and their 95% confidence intervals. RESULTS: A total of 24 studies were included in the meta-analysis. Among the 42 cancer types covered, incidence was associated with firefighting in US samples for colon, kidney, large intestine, pleura, and prostate cancer, as well as malignant melanoma. There was an increased incidence of Hodgkin's Disease and malignant melanoma and a significantly lower risk of kidney cancer for non-US samples. Significant cancer mortality estimates for US samples included oral/buccal/mouth, other parts of the buccal cavity, pharynx, colon, esophagus, large intestine, lung, Non-Hodgkin's Lymphoma, pancreas, pleura, rectum, and soft tissue sarcoma. No cancer had a significantly higher rate of mortality among non-US samples. CONCLUSIONS: The findings underscore the global cancer burden among firefighters, and indicate that geographically stratifying studies afford a more nuanced risk perspective. Further research should investigate why US firefighters exhibit higher cancer mortality rates compared to international counterparts.

Smoking changes adaptive immunity with persistent effects.

Individuals differ widely in their immune responses, with age, sex and genetic factors having major roles in this inherent variability1-6. 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.

Does metformin reduce the risk of cancer in obesity and diabetes? A systematic review and meta-analysis.

AIM: To evaluate the effect of metformin on cancer incidence in subjects with overweight/obesity and/or prediabetes/diabetes. MATERIALS AND METHODS: We searched MEDLINE, Embase and CENTRAL for randomized controlled trials (RCTs) in adults with overweight/obesity and/or prediabetes/diabetes that compared metformin to other interventions for ≥24 weeks. Independent reviewers selected and extracted data including population and intervention characteristics and new diagnoses of cancer. We used the RoB 2.0 risk-of-bias tool and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework to assess risk of bias and certainty of evidence. RESULTS: From 14 895 records after removal of duplicates, 27 trials were included, providing a total of 10 717 subjects in the metformin group and 10 003 in the control group, with 170 and 208 new cases of cancer, respectively. Using a random-effects model, the relative risk was 1.07 (95% confidence interval 0.87-1.31), with similar results in subgroup analyses by study duration or effect of control intervention on weight. Risk of bias in most studies was low, and no evidence of publication bias was found. Trial sequential analysis provided evidence that the cumulative sample size was large enough to exclude a significant effect of metformin on cancer incidence. CONCLUSIONS: Metformin did not reduce cancer incidence in RCTs involving subjects with overweight/obesity and/or prediabetes/diabetes.