Risk Factor For Development Of Cancer Research Articles

P0374 Prevalence, risk factors and clinical outcomes of malignancies in patients with Inflammatory Bowel Disease: a case-control study

Abstract Background Up to 30% of patients with inflammatory bowel disease (IBD) develop malignancies during their disease course whichconstitutes the second cause of death, after cardiovascular diseases (1,2), similar to the general population. The present study aims to investigate the prevalence, risk factors and clinical outcomes of malignancies in patients with IBD. Methods This is a retrospective study, based on prospectively recorded data from the IBD registries of two tertiary centres from 2012-2022. Patients with IBD who developed a malignancy were compared with patients with IBD without malignancies [matching 1:3 according to sex, IBD diagnosis (Ulcerative Colitis; UC, Crohn’s Disease; CD) and age (±5 years)]. Results From 2.382 IBD patients, 107 (4.5%) were diagnosed with cancer (CA) [49 (45.8%) females, 54 (50.5%) CD, median (IQR) age 61 (51.3-69.8) years and median IBD duration 10 (0-40) years at CA diagnosis] and these were matched with 321 patients with IBD who did not develop any type of CA. The majority were extra-intestinal CAs, whereas only 12 (11.2%) were diagnosed with colorectal CA. The most common extraintestinal CAs were thyroid (17, 15.5%) and prostate (17, 15.5%) followed by lung (12, 10.9%), breast (9, 8.2%) and non-melanoma skin cancer (9, 8.2%) while other types like kidney CA or cholangiocarcinoma were represented with lower rates. In the univariate analysis shorter IBD duration, inflammatory CD phenotype, ileal CD location, and treatment with other than anti-TNF biologics were protective, whereas colonic CD location and duration of treatment with immunomodulators (IMMs) were risk factors for CA development. In the multivariate analysis only inflammatory CD phenotype (OR 0.25, CI 95%0.10-0.64) and colonic CD location (OR 3.73, CI 95%1.23-11.34) remained significant (Table 1). Twelve patients (11.2%) had CA recurrence and 19 (17.8%) passed away because of the CA, with most events occurring within 50 months from CA diagnosis. In 36 patients (33.6%) IBD therapy was modified after CA diagnosis (biologics and/or IMMs ceased). However, biologics or IMM were introduced in 24.3% after a median time of 3.5 (0-18) years from CA diagnosis but their use was not associated with negative outcomes [neither on survival (p = 0.0385) nor CA recurrence (p= 0.1680)] (Figure 1). Conclusion The prevalence of malignancy in patients with IBD that are followed up in tertiary referral centers in Crete is 4.5%. CD disease phenotype (inflammatory behavior and colonic location) is associated with the development of malignancies while no association with biologics and/or immunomodulators exposure was found. Initiation of biologics or IMMs after CA diagnosis was not associated with an adverse impact neither on survival nor on CA recurrence.

Preventive and Adjunctive Therapeutic Roles of Immune Optimization for Cancer Management: A Mini-review

Abstract Pathogenesis of cancers encompasses a wide array of immunological processes underscored by immune dysfunction. Immuno-toxic lifestyle habits (poor diet, inadequate sleep, and lack of exercise) are risk factors for cancer development. Immune optimization interventions are useful for cancer prevention and management. T-cell dysfunction disease mediating models describing immunopathogenesis of immune-mediated inflammatory diseases exist. However, they do not highlight inflammatory dysfunctional processes underlying the diseases concerning toxin-mediated epigenetic T-cell dysfunction. Online searches were conducted on databases such as Google Scholar, PubMed, Biomed Central, and SciELO. Articles were reviewed using keywords such as Cancer, Immune optimization/dysfunction, T lymphocyte activation/dysfunction, and inflammatory cytokines. There is a putative T-cell toxin-mediated dysfunction disease model for multiple endocrine neoplasia, which may apply to other cancers. The putative disease model may be validated by multiomic and radiological studies. Validation of the putative disease model should pave the way for a better understanding of the pathogenesis of cancers.

Perceptions and Outcomes of Older Adults Following a Cancer Prevention Educational Seminar

Introduction: 19.9 million new cancer cases and 9.7 million cancer deaths occurred globally in 2023. 90-95% of cancers originate from environment and lifestyle choices. Age is a prominent non-modifiable risk factor for cancer development, so it is essential that older adults are informed on lifestyle factors affecting their cancer risk. Physical therapists (PTs) play a major role in educating and advocating for healthy cancer preventive behaviors. The purpose of this study was to describe outcomes of an educational intervention relating to cancer prevention in community-dwelling older adults. Methods: Investigators developed and delivered a cancer prevention educational seminar relevant to exercise, nutrition, sleep, stress management, and skin care. Twelve adults ≥ 65 years of age completed pre and post surveys. Data were analyzed using descriptive statistics. Comparison of variables between the pre and post surveys were performed to determine intervention impact using measures of central tendency. P-values were analyzed using a Wilcoxon matched pairs signed-rank test. Significance was set at ≤ .05. Results: Statistically significant improvements in beliefs, confidence, and/or knowledge regarding prevention were noted in all topic areas. Discussion: The educational seminar demonstrated positive outcomes for older adults’ knowledge, confidence, and attitudes about healthy behaviors to prevent cancer and underscores the necessity for preventive rehabilitative services provided by PTs. Conclusion: A single-episode educational seminar on the prevention of cancer through the implementation of healthy behaviors in the domains of exercise, nutrition, sleep, stress management, and skin care can precipitate positive changes in knowledge, confidence, and perceptions of older, community-dwelling adults.

Hyperactive Dendritc Cells Redirect Aged Antitumor Immunity.

Aging is one of the biggest risk factors for cancer development. More than 85% of all cancers occur in individuals above 55 years old, often accompanied by age-associated immune defects. Previous studies on the tumor microenvironment during aging have identified several factors, such as the roles of fibroblasts, immunosuppression, and metastasis. However, the aging-associated defects in antitumor immunity, particularly with regard to T cells, remain underexplored. Recent findings by Zhivaki and colleagues suggest that age-related immune defects affecting antitumor responses involve reduced levels of CD8+ T cells and compromised dendritic cell (DC) functions such as antigen presentation and migration. Their study demonstrates that a hyperactive DC vaccine can restore DC functions in older mice. Furthermore, these hyperactive DCs, characterized by increased IL1β production and better migratory capability to the lymph node, promote the development of cytolytic CD4+ T cells exhibiting Th1-like phenotypes. This research reveals mechanisms underlying the response to hyperactive DC vaccines in older mice and highlights the critical role of cytolytic CD4+ T cells as substitutes for CD8+ T cells in driving antitumor immunity and achieving long-term tumor control in older mice.

Cancer and the Microbiome of the Human Body.

Cancer remains a public health concern worldwide, with its incidence increasing worldwide and expected to continue growing during the next decades. The microbiome has emerged as a central factor in human health and disease, demonstrating an intricate relationship between the microbiome and cancer. Although some microbiomes present within local tissues have been shown to restrict cancer development, mainly by interacting with cancer cells or the host immune system, some microorganisms are harmful to human health and risk factors for cancer development. This review summarizes the recent evidence concerning the microbiome and some of the most common cancer types (i.e., lung, head and neck, breast, gastric, colorectal, prostate, and cervix cancers), providing a general overview of future clinical approaches and perspectives.

Cadmium Exposure and Risk of Pancreatic Cancer: A Protocol of Systematic Review and Meta-analysis

Background: Pancreatic cancer is a devastating disease with a poor prognosis, and its etiology involves a complex interplay of genetic, environmental, and lifestyle factors. Among environmental factors, cadmium, a toxic heavy metal, has been implicated in carcinogenesis and is found in various industrial processes, tobacco smoke, and certain foods. Previous studies examining the association between cadmium exposure and pancreatic cancer risk have reported inconsistent findings, necessitating a systematic review and meta-analysis to clarify this relationship. Methods: A systematic search was conducted following PRISMA guidelines to identify relevant studies from electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, Scopus, and Google Scholar. Eligible studies included observational designs (cohort, case-control, cross-sectional) that investigated the association between cadmium exposure and pancreatic cancer risk in human populations. Data extraction, risk of bias assessment, and meta-analysis were conducted using established protocols. Subgroup analyses were performed based on study characteristics and exposure assessment methods. Results: The systematic review and meta-analysis included a comprehensive assessment of the existing literature on cadmium exposure and pancreatic cancer risk. Pooled analysis of eligible studies revealed a potential association between cadmium exposure and an increased risk of pancreatic cancer. However, the magnitude and consistency of this association varied across studies, highlighting the complexity of environmental exposures and their impact on cancer risk. Subgroup analyses and sensitivity analyses were conducted to explore sources of heterogeneity and assess the robustness of the results. Conclusion: This systematic review and meta-analysis contribute to the current understanding of the relationship between cadmium exposure and pancreatic cancer risk. While the findings suggest a potential association, further research is needed to elucidate the underlying mechanisms and clarify the role of cadmium in pancreatic carcinogenesis. These results underscore the importance of environmental risk factors in cancer development and highlight the need for public health interventions aimed at reducing cadmium exposure and improving cancer prevention strategies.

Trimethylamine N-oxide promotes the proliferation and migration of hepatocellular carcinoma cell through the MAPK pathway

Trimethylamine-n-oxide (TMAO) is a metabolite of intestinal flora following the consumption of phosphatidylcholine-rich foods. Clinical cohort studies have shown that plasma TMAO may be a risk factor for cancer development, including hepatocellular carcinoma (HCC), but fundamental research data supporting this hypothesis are lacking. In this study, HCC cells were treated with TMAO in vivo and in vitro to evaluate the effect on some indicators related to the malignancy degree of HCC, and the relevant molecular mechanisms were explored. In vitro, TMAO promoted the proliferation and migration of HCC cells and significantly upregulated the expression of proteins related to epithelial–mesenchymal transformation (EMT). In vivo, after HCC cells were inoculated subcutaneously in nude mice given water containing TMAO, the tumors grew faster and larger than those in the mice given ordinary water. The immunohistochemistry analysis showed that proliferation, migration and EMT-related proteins in the tumor tissues were significantly upregulated by TMAO. Furthermore, TMAO obviously enhanced the phosphorylation of MAPK signaling molecules in vivo and in vitro. In conclusion, TMAO promotes the proliferation, migration and EMT of HCC cells by activating the MAPK pathway.

Magnetic beads-based nanozyme for portable colorimetric biosensing of Helicobacter pylori

Cancer continues to be a significant global health issue with one in six deaths linked to the disease despite advancements in cancer detection and treatment. Recently, Helicobacter pylori (H. pylori) was identified as a risk factor for cancer development. This gram-negative bacterium is associated with gastric conditions, including stomach cancer. Although the exact transmission methods of this bacterium are still unclear, studies suggest that waterborne transmission is possible. This study focuses on the development of a colorimetric nanomaterial-based paper biosensor for specific H. pylori detection using H. pylori extracellular proteases as biomarkers. The biosensor utilizes a unique substrate labeled with magnetic nanobeads and bound to a gold sensing platform. The biosensor's limit of detection (LOD) of 100 CFU/mL, selectivity, stability, and ability to detect H. pylori in clinical specimens were evaluated, demonstrating promising results in terms of sensitivity and specificity. In comparison to traditional methods, this biosensor offers advantages in simplicity and ease of use, making it appropriate for on-site detection in both environmental and clinical settings.

DNA Methylation and p53 Immunohistochemistry as Prognostic Biomarkers for Vulvar Lichen Sclerosus

Vulvar lichen sclerosus (LS) is an inflammatory dermatosis that can progress to human papillomavirus (HPV)-independent vulvar intraepithelial neoplasia (HPVi VIN) and vulvar squamous cell carcinoma (VSCC). Although LS has a much lower cancer risk compared with HPVi VIN (5% vs 50%, respectively), its incidence is significantly higher. Therefore, there is a clinical need to identify LS patients with an increased cancer risk. Our objective was to study the value of DNA methylation and p53 immunohistochemistry (IHC) as prognostic biomarkers for progression to cancer in patients with LS. Vulvar tissues from 236 patients were selected, including 75 LS and 68 HPVi VIN, both with and without cancer development, 32 VSCC, and 61 healthy vulvar controls. Samples were subjected to p53 IHC and DNA methylation analysis of a 3-gene marker panel containing ZNF582, SST, and miR124-2. Methylation levels and p53 IHC status (mutant or wild-type) were assessed and compared among all disease categories. Odds ratios were determined to identify whether the biomarkers were associated with progression to cancer in patients with LS. The highest methylation levels were found in HPVi VIN and VSCC, followed by LS and healthy vulvar controls. The largest heterogeneity in methylation levels was observed in LS cases. In fact, the 3-marker panel tested positive in 70% of LS, which progressed to VSCC vs only 17% of LS in patients without cancer development (P = .002). Also, mutant p53 IHC was observed more frequently in LS with progression to VSCC compared with nonprogressive LS cases (42% vs 3%, respectively, P = .001). Multivariable analysis identified a mutant p53 status as the only independent risk factor for cancer development in LS (odds ratio: 34.0, 95% CI: 1.4-807.4). In conclusion, DNA methylation testing and p53 IHC show strong potential as prognostic biomarkers for the identification of LS patients at high risk of progression to cancer.

Smoking cessation counselling patterns in cancer patients - survey of Lebanese physicians.

Tobacco smoking is a known risk factor for cancer development and smoking cessation can lower this risk and improve outcomes in some cancer patients. Despite that, many cancer patients do not quit smoking after a cancer diagnosis, and smoking cessation counselling is still not routinely provided in cancer care. The aim of this study is to examine patterns in smoking cessation counselling to cancer patients by their treating physicians. A self-administered, web-based (mobile-friendly), anonymous questionnaire was developed on LimeSurvey and sent by e-mail to Lebanese physicians of different specialties between June 2020 and January 2022. Data were analysed using SPSS and associations between the different items were determined using the χ2 test. A total of 146 physicians filled out the questionnaire. Almost all physicians ask cancer patients about their smoking status, but only 45.9% provide smoking cessation counselling, and only 24% refer patients to smoking cessation counselling programs. Only 27.4% of all respondents have received formal smoking cessation training, and only 27.4% feel capable of providing smoking cessation counselling in their clinic. Specifically, family medicine physicians were more likely to provide smoking cessation counselling in the clinic (69%), more likely to refer patients to a smoking cessation counselling program (44%), and more likely to have received formal smoking cessation counselling training (67%) and more likely to feel capable of providing smoking cessation counselling (93%). Lack of training, lack of knowledge of available programs and the lack of availability of enough programs are leading obstacles contributing to low rates of smoking cessation counselling in cancer patients as reported by the physicians. Our data reveals a deficiency in smoking cessation counselling and referral of cancer patients to smoking cessation counselling programs in our region. This highlights the need for dedicated smoking cessation counselling training for practicing physicians and physicians in training.

Onco-Hypertension: A Continuously Developing Field between Cancer and Hypertension.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension (HT), which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary HT related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, HT per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, particularly thiazide diuretics, which may increase the risk of skin cancer. As a result, in light of the similar risk factors and overlapping pathophysiological mechanisms between HT and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

Qualitative and quantitative changes in mitochondrial DNA associated with cervical cancer: A comprehensive review.

Cervical cancer is the fourth most commonly diagnosed cancer in women and is considered a preventable disease, as vaccination and screening programs effectively reduce its incidence and mortality rates. Disease physiopathology and malignant cell transformation is a complex process, but it is widely known that high-risk HPV (hrHPV) infection is a necessary risk factor for cancer development. Mitochondria, cell organelles with important bioenergetic and biosynthetic functions, are important for cell energy production, cell growth, and apoptosis. Mitochondrial DNA is a structure that is particularly susceptible to quantitative (mtDNA copy number variation) and qualitative (sequence variations) alterations that are associated with various types of cancer. Novel biomarkers with diagnostic and prognostic value in cervical cancer can be evaluated to provide higher specificity and complement hrHPV molecular testing, which is the most recommended method for primary screening. In accordance with this, this review aimed to assess mitochondrial alterations associated with cervical cancer in clinical cervicovaginal samples, in order to unravel their possible role as specific diagnostic and prognostic biomarkers for cervical malignancy, and also to guide the understanding of their involvement in carcinogenesis, HPV infection, and disease progression.

Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry-a historical cohort study.

Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk. The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan's Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history. The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44years [interquartile range (IQR) = 34-55] years. The median past maximum glucocorticoid dose was 40mg/day [IQR = 30-60mg/day], and the SDI at registration was 1 [IQR = 0-2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74-1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42-3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47-2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41-4.66). The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development.

What are we doing concretely for the food prevention of cancer? Nutrition between scientific evidence and myopic policies.

Scientific research has often investigated the role of diet as a risk factor for cancer development. It is well known that cancer has a multifactorial origin in which several factors are involved: genetic predisposition, dietary factors, personal habits, and infectious and environmental factors. In this Commentary, the role of diet in cancer is discussed following the scientific evidence suggesting that excessive consumption of red meat and processed foods is correlated with a greater risk of contracting cancer. Nevertheless, public health strategies on nutrition in cancer prevention are struggling to take off. The decision to pursue a healthier diet, along with a healthier lifestyle, often comes when the cancer diagnosis is made and not before. On the other hand, scientific evidence demonstrates how nutritional support is increasingly important during oncological treatments. This paper highlights how far we are still from the global adoption of a healthy and sustainable food style from a health, economic, social and environmental perspective. Additionally, it highlights the ancient vision of the role of nutrition on cancer development in which diet is seen only as a possible risk factor, underestimating the protective role in terms of cancer prevention and the modulatory one once the oncological diagnosis has been made.

Causal association of dietary factors with five common cancers: univariate and multivariate Mendelian randomization studies.

Daily dietary habits are closely related to human health, and long-term unhealthy dietary intake, such as excessive consumption of alcohol and pickled foods, may promote the development of cancers. However, comprehensive research on the causal relationship between dietary habits and cancer is lacking. Therefore, this study aimed to reveal the potential causal link between dietary risk factors and the prognosis of cancer-related to genetic susceptibility. GWAS (Genome-Wide Association Studies) summary data on dietary habits and five common types of cancer and their pathological subtypes were obtained from the UK Biobank and various cancer association consortia. A univariable two-sample Mendelian randomization (UVMR) and FDR correction analysis was conducted to explore the causal relationships between 45 dietary habits and five common types of cancer and their histopathological subtypes. In addition, multivariable Mendelian randomization analysis (MVMR) was performed to adjust for traditional risk factors for dietary habits, and the direct or indirect effects of diet on cancer were evaluated. Finally, the prognostic impact of selected instrumental variables on cancer was analyzed using an online data platform. In the UVMR analysis, four dietary habits were identified as risk factors for cancer, while five dietary habits were identified as protective factors. Among the latter, one dietary habit showed a significant association with cancer even after FDR correction, indicating a potential causal relationship. The MVMR analysis revealed that weekly beer and cider intake, may act as an independent risk factor for cancer development. Other causal associations between dietary habits and cancer risk may be mediated by intermediate factors. In the prognostic analysis, the SNPs (Single Nucleotide Polymorphisms) of average weekly beer and cider intake were set as independent risk factors and were found to significantly impact overall survival (OS) and cancer-specific survival (CSS) in lung cancer. This causal relationship study supports the notion that adjusting daily dietary habits and specific dietary interventions may decrease the risk of cancer.

Epigenetic contribution to the relationship between obesity and cancer.

Obesity and cancer are two major health issues all around the world due to their elevated prevalence. Several experimental and epidemiological studies have demonstrated the relationship between obesity and cancer, in which obesity is considered a risk factor for cancer development. The ultimate goal of knowing the epigenetic contribution to the relationship between obesity and cancer is to find the method of intervention or treatment of obesity and cancer. Therefore, providing the most general perspective on epigenetic contribution to the relationship between obesity and cancer is necessary. Obesity is closely related to some common cancers that are currently encountered, including breast, esophagus, liver, kidney, uterus, colorectal, pancreatic, and gallbladder. Obesity has a significant impact that increases the risk of cancer deaths and thereby indirectly affects the choice of treatment. It is estimated that about 4-8% of cancer cases are caused by obesity. In particular, the basic mechanism to understand the relationship between cancer is very complicated and has not been fully understood. This work is aimed at summarizing the current knowledge of the role of epigenetic regulation in the relationship between obesity, and potential applications.

Rising global burden of cancer attributable to high BMI from 2010 to 2019

BackgroundHigh body mass index (BMI) is a major risk factor for cancer development, but its impact on the global burden of cancer remains unclear. MethodsWe estimated global and regional temporal trends in the burden of cancer attributable to high BMI, and the contributions of various cancer types using the framework of the Global Burden of Disease Study. ResultsFrom 2010 to 2019, there was a 35 % increase in deaths and a 34 % increase in disability-adjusted life-years from cancers attributable to high BMI. The age-standardized death rates for cancer attributable to high BMI increased over the study period (annual percentage change [APC] +0.48 %, 95 % CI 0.22 to 0.74 %). The greatest number of deaths from cancer attributable to high BMI occurred in Europe, but the fastest-growing age-standardized death rates and disability-adjusted life-years occurred in Southeast Asia. Liver cancer was the fastest-growing cause of cancer mortality (APC: 1.37 %, 95 % CI 1.25 to 1.49 %) attributable to high BMI. ConclusionThe global burden of cancer-related deaths attributable to high BMI has increased substantially from 2010 to 2019. The greatest increase in age-standardized death rates occurred in Southeast Asia, and liver cancer is the fastest-growing cause of cancer mortality attributable to high BMI. Urgent and sustained measures are required at a global and regional level to reverse these trends and slow the growing burden of cancer attributed to high BMI.

Obesity is an independent risk factor for cancer development following diagnosis of dermatomyositis

Patients with dermatomyositis (DM) are at an increased risk of cancer development, especially around the time of diagnosis of DM. Obesity is also a risk factor in the general population for cancer development. This study aimed to assess the association between cancer in DM patients with and without obesity as defined by ICD code and BMI data. In this analysis of patients with DM, logistic regression modeling of the odds of cancer outcome was performed for patients with DM and obesity compared to those without obesity, adjusted for age and sex. A total of 12,722 patients with DM were identified, of whom 6,055 had available BMI data. DM patients who were coded obese at any point had significantly higher odds 1.98 (95 % Confidence interval (CI) 1.70, 2.30) of a subsequent cancer diagnosis. This association was also found in the subgroup analysis with available BMI where patients with obesity (BMI ≥30 kg/m2) had an increased odds of cancer 1.23 (1.02, 1.49) when compared to patients with BMI <30 kg/m2 with DM. In time to event analysis any obesity code was associated with a 16 % increased hazard of cancer (adjusted hazard ratio 1.16 [95 % CI 1.02, 1.31]). Overall, the most frequent type of cancer was breast cancer, however patients with DM and obesity had higher frequencies of lymphoma, colorectal, melanoma, uterine, renal cancers compared to patients with DM without obesity.

The role of oral microbiota in cancer.

Cancer remains a significant global challenge, with an estimated 47% increase in cancer patients from 2020 to 2040. Increasing research has identified microorganism as a risk factor for cancer development. The oral cavity, second only to the colon, harbors more than 700 bacterial species and serves as a crucial microbial habitat. Although numerous epidemiological studies have reported associations between oral microorganisms and major systemic tumors, the relationship between oral microorganisms and cancers remains largely unclear. Current research primarily focuses on respiratory and digestive system tumors due to their anatomical proximity to the oral cavity. The relevant mechanism research mainly involves 47% dominant oral microbial population that can be cultured in vitro. However, further exploration is necessary to elucidate the mechanisms underlying the association between oral microbiota and tumors. This review systematically summarizes the reported correlations between oral microbiota and common cancers while also outlining potential mechanisms that may guide biological tumor treatment.

Mutational landscape of intestinal crypt cells after long-term in vivo exposure to high fat diet

Obesity is a modifiable risk factor in cancer development, especially for gastrointestinal cancer. While the etiology of colorectal cancer is well characterized by the adenoma-carcinoma sequence, it remains unclear how obesity influences colorectal cancer development. Dietary components of a high fat diet along with obesity have been shown to modulate the cancer risk by perturbing the homeostasis of intestinal stem cells, yet how adiposity impacts the development of genomic instability has not been studied. Mutational signatures are a powerful way to understand how a complex biological response impacts genomic stability. We utilized a mouse model of diet-induced obesity to study the mutational landscape of intestinal crypt cells after a 48-week exposure to an experimental high fat diet in vivo. By clonally enriching single crypt derived cells in organoid culture and obtaining whole genome sequences, we analyzed and compared the mutational landscape of intestinal epithelial cells from normal diet and high fat diet mice. Single nucleotide substitution signatures and indel signatures present in our cohort are found equally active in both diet groups and reflect biological processes of normal aging, cellular replication, and oxidative stress induced during organoid culturing. Thus, we demonstrate that in the absence of activating mutations or chemical exposure, high fat diet alone is not sufficient to increase genomic instability.