Risk Factor For Development Of Cancer Research Articles

Does OSA Increase Risk for Cancer?: A Large Historical Sleep Clinic Cohort Study

The relationship between OSA and cancer is unclear. What is the association between OSA and cancer prevalence and incidence in a large Western Australian sleep clinic cohort (N= 20,289)? OSA severity was defined by apnea-hypopnea index (AHI) and nocturnal hypoxemia (duration and percentage at oxygen saturation< 90%) measured by in-laboratory polysomnogram. Measures of potential confounding included age, sex, BMI, smoking, socioeconomic status, and BP. Outcomes were determined from the Western Australian cancer and death registries. Analyses were confined within periods using consistent AHI scoring criteria: January 1, 1989, to July 31, 2002 (American Sleep Disorders Association [ASDA] criteria), and August 1, 2002, to June 30, 2013 (Chicago criteria). We examined associations of AHI and nocturnal hypoxemia with cancer prevalence using logistic regression and cancer incidence using Cox regression analyses. Cancer prevalence at baseline was 329 of 10,561 in the ASDA period and 633 of 9,728 in the Chicago period. Nocturnal hypoxemia but not AHI was independently associated with prevalent cancer following adjustment for participant age, sex, BMI, smoking, socioeconomic status, and BP. Of those without prevalent cancer, cancer was diagnosed in 1,950 of 10,232 (ASDA) and 623 of 9,095 (Chicago) participants over a median follow-up of 11.2 years. Compared with the reference category (no OSA, AHI< 5 events per hour), univariable models estimated higher hazard ratios for cancer incidence for mild (AHI 5-15 events per hour), moderate (AHI 15.1-30 events per hour), and severe (AHI > 30 events per hour) OSA. Multivariable analyses consistently revealed associations between age and, in some cases, sex, BMI, and smoking status, with cancer incidence. After adjusting for confounders, multivariable models showed no independent association between OSA severity and increased cancer incidence. Nocturnal hypoxemia is independently associated with prevalent cancer. OSA severity is associated with incident cancer, although this association seems secondary to other risk factors for cancer development. OSA is not an independent risk factor for cancer incidence.

Considerations and analysis of the implementation of oncogeriatrics in Chile and its importance: Review of current literature.

The Chilean census of 2017 reported that 11.4% of the local population are 65years or older, and according to the National Institute of Statistics (INE) the current expectancy of life in Chile is 76years for men and 81years for women respectively. Cancer in Chile is a major public health problem. Aging is a significant risk factor for cancer development which added to the improved life expectancy, it increases the incidence of cancer. In 2040, new cancer cases will increase from 19.3 to 30.2 million worldwide. Older people are a heterogeneous group requiring specialized and individualized management. Chronological age does not necessarily correlate with physiological age. More than half of the geriatric patients with cancer have at least one comorbidity which is relevant when defining a cancer treatment. Likewise, polypharmacy is frequent and is an important issue to consider in people with cancer due to the risk associated with drug interactions. Oncogeriatric assessment consists of a comprehensive multidimensional evaluation, including functional and biopsychosocial issues, addressing aspects of the neoplastic disease such as the risk of toxicities due to systemic therapy and life expectancy. This tool has proven to be helpful in the diagnosis of conditions that are not evident in a routine oncological evaluation, such as geriatric syndromes, frailty, functional dependence, and cognitive impairment among others, which have an impact when deciding on therapy, predicting risks of treatment toxicity and mortality. In this article we aim to describe the current situation of Oncogeriatrics and to provide epidemiological information about cancer in the elderly population in Chile attempting to highlight the importance of the Oncogeriatrics units, within cancer departments, for a better decision taking in the elderly cancer patient.

Protein homeostasis in aging and cancer.

Aging is a major risk factor for cancer development. As dysfunction in protein homeostasis, or proteostasis, is a universal hallmark of both the aging process and cancer, a comprehensive understanding of the proteostasis system and its roles in aging and cancer will shed new light on how we can improve health and quality of life for older individuals. In this review, we summarize the regulatory mechanisms of proteostasis and discuss the relationship between proteostasis and aging and age-related diseases, including cancer. Furthermore, we highlight the clinical application value of proteostasis maintenance in delaying the aging process and promoting long-term health.

P768 The prevalence and risk factors for malignancies in patients with inflammatory bowel disease in Crete : a case control study

Abstract Background There is evidence that about 30% of the patients with inflammatory bowel disease (IBD) develop malignancies whichconstitute the second cause of death, after cardiovascular diseases, such as in general population. Methods The aim of this study was to investigate the prevalence and risk factors for malignancies in IBD patients followed in two tertiary centers. It was a retrospective analysis of prospectively recorded data in an established IBD registry for seven years (06/2015 to 06/2022). IBD patients with malignancies were compared with controls-IBD patients without malignancies [matching 1:3 according to sex, IBD diagnosis (Ulcerative Colitis; UC, Crohn’s Disease; CD) and age (±5 years)] so as to elucidate possible risk factors for cancer (CA) development in these individuals. Results From a total of 2.382 IBD patients of the IBD registry in University Hospital and Venizeleio General Hospital of Heraklion in Crete, 107 (4.5 %) were diagnosed with CAs during their follow-up whereas 22 (0.92 %) had a history of CA before IBD diagnosis. Demographic, clinical and therapeutic data for the total of 428 patients (107 with CA and 321 without CA) are presented in Table 1. Among patients with CA, 49 (45.8%) were females, 54 (50.5%) had CD, the median age of CA diagnosis was 61 years (51.3-69.8) and the median IBD duration was 10 years (3-20). Thirty-two (29.9 %) of the CA-IBD patients had known familial history of CA and 28 (26.1 %) were active smokers whereas 46 (42.9 %) were ex-smokers. Twenty-nine patients (27.1 %) were exposed to immunomodulators, 32 (29.9 %) to anti-TNFs, 20 (18.7 %) to other biologics and 16 (14.9 %) to combination treatment. The majority of CA cases were extra-intestinal, only 12 (11.2 %) had colorectal cancer (CRC) and 11 (10.3 %) had a CA recurrence whereas 19 (17.8 %) died from the CA. In the univariate analysis the median IBD duration (OR 0.96, CI 95%0.94- 0.99), inflammatory phenotype in CD (OR 0.46, CI 95% 0.23-0.93) and treatment with other biologics (other than ant-TNFs) (OR 0.50, CI 95%0.29- 0.86) were protective factors, whereas colonic location in CD (OR 3.24, CI 95% 1,49-7,04) found to be a risk factor for CA development(Table 1). No association with disease characteristics, smoking habits, family history of CA and extra intestinal manifestations was found. In the multivariate analysis only CD inflammatory phenotype (OR 0.28, CI 95%0.09-0.58) was a protective factor whereas colonic location (OR 4.8, CI 95% 1.81-12.79) remained a risk factor for malignancies (Table 2). Conclusion The prevalence of malignancy in IBD patients in Crete is 4.5%. It seems that in CD disease phenotype is associated with the development of malignancies. Non association with the used medications was found.

Adipokines and epithelial-mesenchymal transition (EMT) in cancer.

Obesity is a significant risk factor for cancer development. Within the tumor microenvironment, adipocytes interact with cancer cells, immune cells, fibroblasts and endothelial cells, and orchestrate several signaling pathways by secreting bioactive molecules, including adipokines. Adipokines or adipocytokines are produced predominantly by adipocytes and function as autocrine, paracrine and endocrine mediators. Adipokines can exert pro- and anti-inflammatory functions, and they play a pivotal role in the state of chronic low-grade inflammation that characterizes obesity. Epithelial-mesenchymal transition (EMT), a complex biological process whereby epithelial cells acquire the invasive, migratory mesenchymal phenotype is well-known to be implicated in cancer progression and metastasis. Emerging evidence suggests that there is a link between adipokines and EMT. This may contribute to the correlation that has been documented between obesity and cancer progression. This review summarizes the existing body of evidence supporting an association between the process of EMT in cancer and the adipokines leptin, adiponectin, resistin, visfatin/NAMPT, lipocalin-2/NGAL, as well as other newly discovered adipokines including chemerin, nesfatin-1/nucleobindin-2, AZGP1, SFRP5 and FABP4.

Exosome-like vesicles released from ob/ob mouse adipose tissue enhance cell survival of cells with radiation-induced genomic instability.

Multiple epidemiological studies have shown that obesity is a serious risk factor for cancer development. While the underlying mechanisms between obesity and cancer are still unknown, obesity disrupts the role of adipocytes in energy homeostasis, and the alteration of adipokine, insulin and sex steroid signaling. Recently, it has been identified that adipose tissue-derived exosome-like vesicles (ELVs) regulate metabolic homeostasis. In this study, we collected ELVs from adipose tissue of an obese mouse (ob/ob) strain and control mouse (C57BL/6) strain, and checked whether adipose ELVs influence radiation-induced cell death on mouse fibroblast cells (m5S). Furthermore, we analyzed the micronucleus (MN) frequency in survived cells after radiation exposure to investigate the effect of ELVs on radiation-induced genomic instability. We first observed that ELVs from control and obese mice showed enhanced colony forming ability in un-irradiated m5S cells. However, enhanced survival was observed only in 3Gy-irradiated m5S cells with obese ELV treatment. Despite no ELV effect on colony size, interestingly, the frequency of MN in survived m5S cells after 3Gy irradiation was elevated when treated obese ELVs compared to control ELVs. These results suggested that obese mouse adipose ELVs could enhance the survival of irradiated cells harboring increased radiation-induced genomic instability.

The Modulatory Effects of Fatty Acids on Cancer Progression

Cancer is the second leading cause of death worldwide and the global cancer burden rises rapidly. The risk factors for cancer development can often be attributed to lifestyle factors, of which an unhealthy diet is a major contributor. Dietary fat is an important macronutrient and therefore a crucial part of a well-balanced and healthy diet, but it is still unclear which specific fatty acids contribute to a healthy and well-balanced diet in the context of cancer risk and prognosis. In this review, we describe epidemiological evidence on the associations between the intake of different classes of fatty acids and the risk of developing cancer, and we provide preclinical evidence on how specific fatty acids can act on tumor cells, thereby modulating tumor progression and metastasis. Moreover, the pro- and anti-inflammatory effects of each of the different groups of fatty acids will be discussed specifically in the context of inflammation-induced cancer progression and we will highlight challenges as well as opportunities for successful application of fatty acid tailored nutritional interventions in the clinic.

Abstract A028: Incidental detection of age-related somatic genomic alterations in blood samples from dogs with and without cancer

Abstract The concept of age-related somatic alterations in the blood or bone marrow of humans, commonly referred to as clonal hematopoiesis of indeterminate potential (CHIP) or age-related clonal hematopoiesis (ARCH), has been well characterized. In humans, these abnormalities tend to be associated with advanced age, often exhibit consistent signal over time, and typically involve recurrent locations in the genome. Though these somatic alterations may be associated with an increased risk of cancer, they do not originate from the tumor when cancer is concurrently present in the body. This study describes early findings that suggest similar age-related somatic alterations may also be present in dogs. Recently, next-generation sequencing-based liquid biopsy testing was developed for cancer detection in dogs. The clinical validation of this test involved 1,100 cancer-diagnosed and presumably cancer-free client-owned dogs. The test has also been performed commercially in thousands of additional dogs since 2021. This recent ability to test large numbers of dogs using liquid biopsy affords an unprecedented opportunity to study the genomic profiles of a broad population of canine subjects. Blood samples from over three thousand dogs ranging in age from 1 to &amp;gt;15 years were used in this analysis. Cell-free DNA (cfDNA) was extracted from the plasma, and genomic DNA (gDNA) was extracted from the white blood cells present in the buffy coat. Both cfDNA and gDNA were analyzed using next-generation sequencing to identify somatic genomic alterations. In a subset of patients, tumor tissue was also available for evaluation. Recurrent variants (e.g., involving CFA6 and CFA25, among others) were identified in the gDNA of a small fraction of patients. These findings occurred more commonly in older dogs and were typically persistent in gDNA across subsequent timepoints (when available) with no significant change in signal over time. When a clinical cancer evaluation was pursued, the majority of dogs with these findings had no evidence of cancer. For those in which cancer was identified, and tumor tissue was available for testing, the genomic profiles of the tumor tissue and gDNA were uncorrelated in almost all cases, suggesting the concomitant presence of age-related somatic alterations was incidental to the patient’s cancer. Additionally, regardless of whether cancer was present in the patient, the variants detected in gDNA were typically not encountered in cfDNA. These findings may be early evidence for the existence of age-related somatic alterations in dogs that potentially resemble the phenomenon of CHIP/ARCH previously observed in humans. Additional studies are ongoing to determine if these incidental findings may represent a risk factor for cancer development in dogs. Citation Format: Dana W.Y. Tsui, Allison L. O'Kell, Todd A. Cohen, Katherine M. Lytle, Kristina M. Kruglyak, Maggie A. Marshall, Carlos A. Ruiz-Perez, John A. Tynan, Susan C. Hicks, Jill M. Rafalko, Daniel S. Grosu, Jason Chibuk, Ilya Chorny, Angela L. McCleary-Wheeler, Andi Flory. Incidental detection of age-related somatic genomic alterations in blood samples from dogs with and without cancer [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A028.

Abstract PR010: Aging-induced reprogramming of the cell of origin defines lung cancer evolution

Abstract Aging is one of the most important risk factors for cancer development. However, our understanding of how aging impacts cancer evolution remains at an early stage. We investigated the evolution of lung adenocarcinoma (LUAD) in aged vs. young KrasLSL-G12D/+; Trp53flox/flox (KP) mice. Surprisingly, we found that LUAD initiation and progression were significantly impaired with aging. Using functional in vivo and in vitro assays, we demonstrated that the loss of tumor-initiating potential could be attributed to a loss of stemness in the alveolar type 2 (AT2) cells, which are the predominant cell of origin for LUAD. We next explored the biology of the tumors that formed in aged KP mice using single-cell transcriptomics. We discovered a distinct compositional landscape of cancer cell subsets in aged lung tumors, revealing a delay in the molecular progression of the cancers and an aging-specific gene expression signature. Interestingly, key components of this gene signature could be traced back to specific epigenetic alterations in the AT2 cells. Furthermore, the aged mouse LUAD signature was highly predictive of patient age in human LUAD, indicating conservation of the age-associated changes across species. We hypothesized that the aging-associated changes in gene expression during LUAD tumorigenesis may underpin delayed tumor progression in the aged KP mice. To test this, we performed an in vivo genetic screen in the autochthonous KP model and identified genetic dependencies that were specific to LUAD in aged or young mice. Our results indicate that aging-associated epigenetic changes in the cell of origin are imprinted on evolving tumors, which determines tumor initiation potential, alters trajectory of tumor evolution, and leads to age-dependent vulnerabilities. These findings suggest that the biology of tumors is fundamentally altered by aging, raising new possibilities for cancer treatment and prevention in patients of different ages. Citation Format: Xueqian Zhuang, Simon Joost, Qing Wang, Melissa Blum, Selena Ding, Zhuxuan Li, Yingqian Zhan, Richard Koche, Emily Wong, Tuomas Tammela. Aging-induced reprogramming of the cell of origin defines lung cancer evolution [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr PR010.

Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells.

In general, the risk of being diagnosed with cancer increases with age; however, the development of estrogen-receptor-positive (ER+) cancer types in women are more closely related to menopausal status than age. In fact, the general risk factors for cancer development, such as obesity-induced inflammation, show differences in their association with ER+ cancer risk in pre- and postmenopausal women. Here, we tested the role of the principal estrogens in the bloodstream before and after menopause, estradiol (E2) and estrone (E1), respectively, on inflammation, epithelial-to-mesenchymal transition (EMT) and cancer stem cell enrichment in the human ER+ cervical cancer cell line HeLa. Our results demonstrate that E1, contrary to E2, is pro-inflammatory, increases embryonic stem-transcription factors (ES-TFs) expression and induces EMT in ER+ HeLa cells. Moreover, we observed that high intratumoural expression levels of 17β-Hydroxysteroid dehydrogenase (HSD17B) isoforms involved in E1 synthesis is a poor prognosis factor, while overexpression of E2-synthetizing HSD17B isoforms is associated with a better outcome, for patients diagnosed with ER+ ovarian and uterine corpus carcinomas. This work demonstrates that E1 and E2 have different biological functions in ER+ gynaecologic cancers. These results open a new line of research in the study of ER+ cancer subtypes, highlighting the potential key oncogenic role of E1 and HSD17B E1-synthesizing enzymes in the development and progression of these diseases.

The higher body mass index is associated with a lower somatic mutation dependency in hepatocellular carcinoma

BackgroundReaching a certain somatic mutation threshold is a prerequisite of neoplastic initiation. High Body Mass Indexes (BMI) have been introduced as an independent risk factor for cancer development. However, there is evidence for lower mutational dependency in obese individuals in some types of cancers. In this study, we conducted a differential mutation analysis among patients with hepatocellular carcinoma (HCC) with different BMI. MethodsMutation annotation files of 158 normal-weights, 112 overweight and 76 obese HCC patients were retrieved from the TCGA-LIHC project using the TCGAbiolinks library [3]. The Ensembl Variant Effect Predictor (VEP) tool was used to further annotate the identified common and exclusive mutations in both BMI categories. The pathway enrichment of the characterized pathogenic mutations in different BMI categories was performed using the KEGG database. ResultHCC patients with normal BMIs showed a significantly higher frequency of pathogenic mutations compared with higher BMI groups. Pathogenic mutations in HCC-associated genes, namely TP53, CTTNB1, ARID2, ARID1A, AXIN1, and NFE2L2 were observed in the three BMI categories. However, they were more frequently targeted in normal-weights. Accordingly, a significantly larger number of mutated genes involved in cancer-associated signaling pathways, including Hepatocellular Carcinoma, PI3K-Akt, MAPK, and p53 were observed in patients with normal body weights compared with the higher BMI groups. In addition to the common targeted pathways among the three BMI groups, cAMP, Wnt, Hippo, and JAK-STAT signaling pathways were shared between normal-weight and overweight patients with HCC., Ras and mTOR signaling pathways were also exclusively targeted in the normal-weight group. ConclusionObese and overweight patients with HCC represent lower mutation dependency to develop HCC. More investigations considering central obesity measures will help to specify the molecular alterations caused by the presence of central fat that may promote tumor progression regardless of BMI.

Evolving DNA repair synthetic lethality targets in cancer.

DNA damage signaling response and repair (DDR) is a critical defense mechanism against genomic instability. Impaired DNA repair capacity is an important risk factor for cancer development. On the other hand, up-regulation of DDR mechanisms is a feature of cancer chemotherapy and radiotherapy resistance. Advances in our understanding of DDR and its complex role in cancer has led to several translational DNA repair-targeted investigations culminating in clinically viable precision oncology strategy using poly(ADP-ribose) polymerase (PARP) inhibitors in breast, ovarian, pancreatic, and prostate cancers. While PARP directed synthetic lethality has improved outcomes for many patients, the lack of sustained clinical response and the development of resistance pose significant clinical challenges. Therefore, the search for additional DDR-directed drug targets and novel synthetic lethality approaches is highly desirable and is an area of intense preclinical and clinical investigation. Here, we provide an overview of the mammalian DNA repair pathways and then focus on current state of PARP inhibitors (PARPi) and other emerging DNA repair inhibitors for synthetic lethality in cancer.

Role of oral microbiome in oral oncogenesis, tumor progression, and metastasis.

Squamous cell carcinoma is the most common malignant tumor of the oral cavity and its adjacent sites, which endangers the physical and mental health of patients and has a complex etiology. Chronic infection is considered to be a risk factor in cancer development. Evidence suggests that periodontal pathogens, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, are associated with oral squamous cell carcinoma (OSCC). They can stimulate tumorigenesis by promoting epithelial cells proliferation while inhibiting apoptosis and regulating the inflammatory microenvironment. Candida albicans promotes OSCC progression and metastasis through multiple mechanisms. Moreover, oral human papillomavirus (HPV) can induce oropharyngeal squamous cell carcinoma (OPSCC). There is evidence that HPV16 can integrate with host cells' DNA and activate oncogenes. Additionally, oral dysbiosis and synergistic effects in the oral microbial communities can promote cancer development. In this review, we will discuss the biological characteristics of oral microbiome associated with OSCC and OPSCC and then highlight the mechanisms by which oral microbiome is involved in oral oncogenesis, tumor progression, and metastasis. These findings may have positive implications for early diagnosis and treatment of oral cancer.

Considerations and Analysis of the Implementation of Oncogeriatrics in Chile and Its Importance

The Chilean census of 2017 reported that 11.4% of the local population are 65 years or older, and according to the National Institute of Statistics (INE) by 2025 20% of the Chilean population will be in this group. Cancer in Chile is a major public health problem. Aging is a significant risk factor for cancer development which added to the improved life expectancy, it increases the incidence of cancer. In 2040, new cancer cases will increase from 19.3 to 30.2 million worldwide. Older people are a heterogeneous group requiring specialized and individualized management. Chronological age does not necessarily correlate with physiological age. More than half of the geriatric patients with cancer have at least one comorbidity which is relevant when defining a cancer treatment. Likewise, polypharmacy is frequent and is an important issue to consider in people with cancer due to the risk associated with drug interactions. Oncogeriatric assessment consists of a comprehensive multidimensional evaluation, including functional and biopsychosocial issues, addressing aspects of the neoplastic disease such as the risk of toxicities due to systemic therapy and life expectancy. This tool has proven to be helpful in the diagnosis of conditions that are not evident in a routine oncological evaluation, such as geriatric syndromes, frailty, functional dependence, and cognitive impairment among others, which have an impact when deciding on therapy, predicting risks of treatment toxicity and mortality.

Adipokines as Regulators of Autophagy in Obesity-Linked Cancer.

Excess body weight and obesity have become significant risk factors for cancer development. During obesity, adipose tissue alters its biological function, deregulating the secretion of bioactive factors such as hormones, cytokines, and adipokines that promote an inflammatory microenvironment conducive to carcinogenesis and tumor progression. Adipokines regulate tumor processes such as apoptosis, proliferation, migration, angiogenesis, and invasion. Additionally, it has been found that they can modulate autophagy, a process implicated in tumor suppression in healthy tissue and cancer progression in established tumors. Since the tumor-promoting role of autophagy has been well described, the process has been suggested as a therapeutic target in cancer. However, the effects of targeting autophagy might depend on the tumor type and microenvironmental conditions, where circulating adipokines could influence the role of autophagy in cancer. Here, we review recent evidence related to the role of adipokines in cancer cell autophagy in an effort to understand the tumor response in the context of obesity under the assumption of an autophagy-targeting treatment.

Essential Roles of Peroxiredoxin IV in Inflammation and Cancer.

Peroxiredoxin IV (Prx4) is a 2-Cysteine peroxidase with ubiquitous expression in human tissues. Prx4 scavenges hydrogen peroxide and participates in oxidative protein folding in the endoplasmic reticulum. In addition, Prx4 is secreted outside the cell. Prx4 is upregulated in several cancers and is a potential therapeutic target. We have summarized historical and recent advances in the structure, function and biological roles of Prx4, focusing on inflammatory diseases and cancer. Oxidative stress is known to activate pro-inflammatory pathways. Chronic inflammation is a risk factor for cancer development. Hence, redox enzymes such as Prx4 are important players in the crosstalk between inflammation and cancer. Understanding molecular mechanisms of regulation of Prx4 expression and associated signaling pathways in normal physiological and disease conditions should reveal new therapeutic strategies. Thus, although Prx4 is a promising therapeutic target for inflammatory diseases and cancer, further research needs to be conducted to bridge the gap to clinical application.

S1471 The Perceived Risk of Lifestyle Choices on Cancer Development Among Obese Adults in the United States

Introduction: Obesity is known to be associated with several comorbidities, including cancer. Reduced fat mass, healthy eating and regular exercise are known ways to minimize obesity-associated inflammation, which is an underlying pathophysiologic mechanism of disease development. It is unknown if obese adults in the United States understand the significance of these lifestyle choices on cancer development. We aimed to evaluate the perception of obese US adults on the influence of obesity, healthy eating and regular exercise on the development of cancer. Methods: We analyzed the 2018 Health Information National Trends Survey (HINTS 5 Cycle 2). Our analytical cohort identified 2,986 respondents in the US (weighted population size = 219,552,371). Respondents rated how much they thought the following factors had an influence on whether a person will develop cancer: (1) Being overweight or obese, (2) Eating healthy food, and (3) Exercising regularly. We used logistic regression analyses to examine the association between respondent BMI categories and whether respondents believed each factor substantially influenced the development of cancer. We used survey weights in all analyses. We calculated odds ratios (OR) and 95% confidence interval (CI). Results: The mean age of the cohort was 48.4 years, 50.1% female, 66.1% White, 10.3% Black, 15.9% Hispanic, 15.8% current smokers, 27.9% with a yearly household income less than $35,000 and 30.4% had a high school education or less. The perception of obese respondents was generally lower in agreeing that these putative risk factors (obesity, healthy eating, and regular exercises) affect cancer development and was statistically significantly lower with identifying obesity as influencing cancer development (Table 1). Conclusion: There is a general suboptimal knowledge about factors that influence cancer development among adults in the United States. This is particularly worse among obese subjects. There is a need for healthcare providers and public health officials to educate the population at large about risk factors for cancer development, particularly among obese subjects. Table 1. - Perceived risk of lifestyle choices on cancer development among US adults by BMI categories Adjusted for age, sex, education, marital status, health insurance, smoking, income, and race Perceived risk on cancer Normal BMI (< 25 kg/m2) Overweight (25-29.9 kg/m2) Obese (≥30 kg/m2) N (%) OR (95% CI) N (%) OR (95% CI) N (%) OR (95% CI) Obesity has a lot of Influence (Yes) 369 (39.2) Reference 349 (29.5) 0.68 (0.45-1.02) 294 (24.6) 0.51 (0.33-0.80) Healthy Eating has a lot of Influence (Yes) 492 (48.0) Reference 470 (42.3) 0.89 (0.58-1.36) 435 (40.5) 0.87 (0.59-1.28) Regular Exercise has a lot of Influence (Yes) 420 (41.3) Reference 411 (36.2) 0.82 (0.56-1.19) 377 (32.7) 0.74 (0.53-1.03)

Regulation of the Innate Immune Response during the Human Papillomavirus Life Cycle.

High-risk human papillomaviruses (HR HPVs) are associated with multiple human cancers and comprise 5% of the human cancer burden. Although most infections are transient, persistent infections are a major risk factor for cancer development. The life cycle of HPV is intimately linked to epithelial differentiation. HPVs establish infection at a low copy number in the proliferating basal keratinocytes of the stratified epithelium. In contrast, the productive phase of the viral life cycle is activated upon epithelial differentiation, resulting in viral genome amplification, high levels of late gene expression, and the assembly of virions that are shed from the epithelial surface. Avoiding activation of an innate immune response during the course of infection plays a key role in promoting viral persistence as well as completion of the viral life cycle in differentiating epithelial cells. This review highlights the recent advances in our understanding of how HPVs manipulate the host cell environment, often in a type-specific manner, to suppress activation of an innate immune response to establish conditions supportive of viral replication.

Alcohol-related diseases and liver metastasis: Role of cell-free network communication.

Alcohol intake is a risk factor for cancer development and metastatic disease progression. Extracellular vesicle (EV)-mediated interorgan communication is assumed to be significant in boosting tumorigenic pathways and disease progression. Recent research indicates that exosomes have a variety of roles in the development of cancer during pathophysiological conditions. The involvement of EV signaling during cancer progression in the alcohol environment is unknown. Therefore, understanding communication networks and the role of EVs as biomarkers can contribute significantly to developing strategies to address the serious public health problems associated with alcohol consumption and cancer.

Aging-based molecular classification and score system in ccRCC uncovers distinct prognosis, tumor immunogenicity, and treatment sensitivity.

ObjectiveAging is a complex biological process and a major risk factor for cancer development. This study was conducted to develop a novel aging-based molecular classification and score system in clear cell renal cell carcinoma (ccRCC).MethodsIntegrative analysis of aging-associated genes was performed among ccRCC patients in the TCGA and E-MTAB-1980 cohorts. In accordance with the transcriptional expression matrix of 173 prognostic aging-associated genes, aging phenotypes were clustered with the consensus clustering approach. The agingScore was generated to quantify aging phenotypes with principal component analysis. Tumor-infiltrating immune cells and the cancer immunity cycle were quantified with the ssGSEA approach. Immunotherapy response was estimated through the TIDE algorithm, and a series of tumor immunogenicity indicators were computed. Drug sensitivity analysis was separately conducted based on the GDSC, CTRP, and PRISM analyses.ResultsThree aging phenotypes were established for ccRCC, with diverse prognosis, clinical features, immune cell infiltration, tumor immunogenicity, immunotherapeutic response, and sensitivity to targeted drugs. The agingScore was developed, which enabled to reliably and independently predict ccRCC prognosis. Low agingScore patients presented more undesirable survival outcomes. Several small molecular compounds and three therapeutic targets, namely, CYP11A1, SAA1, and GRIK4, were determined for the low agingScore patients. Additionally, the high agingScore patients were more likely to respond to immunotherapy.ConclusionOverall, our findings introduced an aging-based molecular classification and agingScore system into the risk stratification and treatment decision-making in ccRCC.