Important Risk Factor For Cancer Research Articles

Diabetes and cancer: two epidemic diseases requiring an opposite therapeutic approach to target cells

Diabetes and cancer are two chronic metabolic diseases with ever-increasing incidence rates worldwide. These disorders can often occur together, as diabetes presents an important risk factor for cancer and some cancers could in turn lead to diabetes. In this perspective article, many more commonalities between diabetes and cancer are highlighted, including the role of lifestyle and environmental factors in the pathogenesis, the presence of a rather long latency period before clinical diagnosis of invasive disease, as well as the ultimate progression to diabetic complications or malignant metastases. Moreover, both of these devastating disorders still lack curative treatment options, whereas several currently approved antidiabetic and anticancer drugs have been originally derived from different natural sources. However, while in the case of diabetes, the main therapeutic goal is to maintain the pancreatic islet mass by preserving β-cells survival, the major purpose of cancer therapy is to kill malignant cells and reduce the neoplastic mass of solid tumors. It is expected that both diabetes and cancer, two systemic diseases with epidemic proportions, would be managed more effectively through an integral approach, considering many different aspects related to their pathogenesis, including also lifestyle changes and dietary modifications.

Associations of combined phenotypic aging and genetic risk with incident cancer: A prospective cohort study.

Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs). Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18-1.27) in men, and 1.26 (1.22-1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10-2.51) for men and 1.94 (1.78-2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = -1.01 in men, p<0.001; Beta = -0.98 in women, p<0.001). Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle. This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).

Associations of combined phenotypic aging and genetic risk with incident cancer: A prospective cohort study

Background:Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer.Methods:Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs).Results:Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18–1.27) in men, and 1.26 (1.22–1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10–2.51) for men and 1.94 (1.78–2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = –1.01 in men, p&lt;0.001; Beta = –0.98 in women, p&lt;0.001).Conclusions:Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle.Funding:This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).

Stratification and prognostic evaluation of breast cancer subtypes defined by obesity-associated genes

ObjectiveBreast cancer was the most common type of cancer among women worldwide, significantly impacting their quality of life and survival rates. And obesity has been widely accepted as an important risk factor for breast cancer. However, the specific mechanisms by which obesity affects breast cancer were still unclear. Therefore, studying the impact mechanisms of obesity as a risk factor for breast cancer was of utmost importance.MethodsThis study was based on TCGA breast cancer RNA transcriptomic data and the GeneCard obesity gene set. Through single and multiple factor Cox analysis and LASSO coefficient screening, seven hub genes were identified. The independent mechanisms of these seven hub genes were evaluated from various aspects, including survival data, genetic mutation data, single-cell sequencing data, and immune cell data. Additionally, the risk prognosis model and the neural network diagnostic model were established to further investigate these seven hub genes. In order to achieve precision treatment for breast cancer (BRCA), based on the RNA transcriptomic data of the seven genes, 1226 BRCA patients were divided into two subtypes: BRCA subtype 1 and BRCA subtype 2. By studying and comparing the immune microenvironment, investigating the mechanisms of differential gene expression, and exploring the mechanisms of subnetworks, we aim to explore the clinical differences in the presentation of BRCA subtypes and achieve precision treatment for BRCA. Finally, qRT-PCR experiments were conducted to validate the conclusions of the bioinformatics analysis.ResultsThe 7 hub genes showed good diagnostic independence and can serve as excellent biomarkers for molecular diagnosis. However, they do not perform well as independent prognostic molecular markers for BRCA patients. When predicting the survival of BRCA patients, their AUC values at 1 year, 3 years, and 5 years are mostly below 0.5. Nevertheless, through the establishment of the risk prognosis model considering the combined effect of the seven hub genes, it was found that the survival prediction of BRCA patients can be significantly improved. The risk prognosis model, compared to the independent use of the seven hub genes as prognostic markers, achieved higher timeROC AUC values at 1 year, 3 years, and 5 years, with values of 0.651, 0.669, and 0.641 respectively. Additionally, the neural network diagnostic model constructed from the 7 genes performs well in diagnosing BRCA, with an AUC value of 0.94, accurately identifying BRCA patients. The two subtypes identified by the seven hub genes exhibited significant differences in survival period, with subtype 1 having a poor prognosis. The differential mechanisms between the two subtypes mainly originate from regulatory differences in the immune microenvironment. Finally, the results of this study’s bioinformatics analysis were validated through qRT-PCR experiments.Conclusion7 hub genes serve as excellent independent biomarkers for molecular diagnosis, and the neural network diagnostic model can accurately distinguish BRCA patients. In addition, based on the expression levels of these seven genes in BRCA patients, two subtypes can be reliably identified: BRCA subtype 1 and BRCA subtype 2, and these two subtypes showed significant differences in BRCA patient survival prognosis, proportion of immune cells, and expression levels of immune cells. Among them, patients with subtype 1 of BRCA had a poor prognosis.

Cervicovaginal microbiota: a promising direction for prevention and treatment in cervical cancer.

Cervical cancer is a common malignancy in women, with high incidence rate and mortality. Persistent infection of high-risk human papillomavirus (HPV) is the most important risk factor for cervical cancer and precancerous lesions. Cervicovaginal microbiota (CVM) plays an essential role in the defense of HPV infections and prevention of subsequent lesions. Dominance of Lactobacillus is the key of CVM homeostasis, which can be regulated by host, exogenous and endogenous factors. Dysbiosis of CVM, including altered microbial, metabolic, and immune signatures, can contribute to persist HPV infection, leading to cervical cancer. However, there is no evidence of the causality between CVM and cervical cancer, and the underlying mechanism remains unexplored. Considering the close correlation between CVM dysbiosis and persistent HPV infection, this review will overview CVM, its role in cervical cancer development and related mechanisms, and the prospects for therapeutic applications.

Impact of Indoor Radon Exposure on Lung Cancer Incidence in Slovenia.

Indoor radon is an important risk factor for lung cancer, as 3-14% of lung cancer cases can be attributed to radon. The aim of our study was to estimate the impact of indoor radon exposure on lung cancer incidence over the last 40 years in Slovenia. We analyzed the distribution of lung cancer incidence across 212 municipalities and 6032 settlements in Slovenia. The standardized incidence ratios were smoothed with the Besag-York-Mollie model and fitted with the integrated nested Laplace approximation. A categorical explanatory variable, the risk of indoor radon exposure with low, moderate and high risk values, was added to the models. We also calculated the population attributable fraction. Between 2.8% and 6.5% of the lung cancer cases in Slovenia were attributable to indoor radon exposure, with values varying by time period. The relative risk of developing lung cancer was significantly higher among the residents of areas with a moderate and high risk of radon exposure. Indoor radon exposure is an important risk factor for lung cancer in Slovenia in areas with high natural radon radiation (especially in the southern and south-eastern parts of the country).

Components of the metabolic syndrome: abdominal obesity and arterial hypertension in the context of the risk of oncological pathology

Introduction Metabolic syndrome (MS) is the most important risk factor for cancer, although the full relationship between MS and cancer remains far from resolved. A number of studies have been conducted that indicate a certain connection between hormonal and inflammatory changes in adipose tissue and cancer.&#x0D; Objectives The aim of the paper was to study was to investigate the incidence of cancer in patients with MS lasting more than 10 years, and the degree of dependence on its components: abdominal obesity (AO) and arterial hypertension (AH).&#x0D; Methods For comparison by the same parameters data from patients without MS were analyzed. The crosstabulation method was used to estimate the odds ratio (OR) of carcinogenesis and 95% confidence intervals (95% CI).&#x0D; Results It was found that in patients with a duration of MS of 13.5±2.41 years, the initiation of oncological diseases was observed in every fifth participant, while in the absence of MS in every fourteenth patient.&#x0D; Conclusion AO is associated with an increased risk of developing hypertension, and both of these conditions are associated with an increased risk of cancer of various localization. The greatest risk was found in MS with grade I obesity in combination with hypertension, as well as with the patient’s age.&#x0D; Bangladesh Journal of Medical Science Vol. 23 No. 02 April’24 Page : 407-417

How does weight gain since the age of 18 years affect breast cancer risk in later life? A meta-analysis

Early life factors are important risk factors for breast cancer. The association between weight gain after age 18 and breast cancer risk is inconsistent across previous epidemiologic studies. To evaluate this association, we conducted a meta-analysis according to PRISMA guidelines and the established inclusion criteria. We performed a comprehensive literature search using Medline (Ovid), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov to identify relevant studies published before June 3, 2022. Two reviewers independently reviewed the articles for final inclusion. Seventeen out of 4,725 unique studies met the selection criteria. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), and all were of moderate to high quality with NOS scores ranging from 5 to 8. We included 17 studies (11 case-control, 6 cohort) in final analysis. In case-control studies, weight gain after age 18 was associated with an increased risk of breast cancer (odds ratio [OR] = 1.25; 95% CI = 1.07–1.48), when comparing the highest versus the lowest categories of weight gain. Menopausal status was a source of heterogeneity, with weight gain after age 18 associated with an increased risk of breast cancer in postmenopausal women (OR = 1.53; 95% CI = 1.40–1.68), but not in premenopausal women (OR = 1.01; 95% CI = 0.92–1.12). Additionally, a 5 kg increase in weight was positively associated with postmenopausal breast cancer risk (OR = 1.12; 95%CI = 1.05–1.21) in case-control studies. Findings from cohort studies were identical, with a positive association between weight gain after age 18 and breast cancer incidence in postmenopausal women (relative risk [RR] = 1.30; 95% CI = 1.09–1.36), but not in premenopausal women (RR = 1.06; 95% CI = 0.92–1.22). Weight gain after age 18 is a risk factor for postmenopausal breast cancer, highlighting the importance of weight control from early adulthood to reduce the incidence of postmenopausal breast cancer.

Vonoprazan: A Review in Helicobacter pylori Infection.

Treatment for the eradication of Helicobacter pylori infection, a leading cause of peptic ulcer disease and an important risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma, is indicated whenever infection is identified. However, treatment success rates with current guideline-recommended proton-pump inhibitor (PPI)-based regimens remain suboptimal, with one potential factor associated with treatment failure being inadequate acid suppression. Vonoprazan (Voquezna®) is a first-in-class potassium-competitive acid blocker with the potential to provide potent and sustained acid suppression. Following clinical trials conducted mainly in Asia (supported by post-marketing experience from Asia) and the phaseIII PHALCON-HP trial conducted in the USA and Europe, vonoprazan is now approved in the USA for use in combination with amoxicillin (dual therapy) or amoxicillin and clarithromycin (triple therapy) for the treatment of H.pylori infection in adults. The vonoprazan-based dual and triple therapy regimens were generally well tolerated in PHALCON-HP. In addition, vonoprazan has advantages including a rapid onset of action and no food effect, making vonoprazan-based dual and triple therapy regimens valuable alternatives to standard PPI-based triple therapy in the treatment of H.pylori infection.

Generalisable deep learning method for mammographic density prediction across imaging techniques and self-reported race.

Breast density is an important risk factor for breast cancer complemented by a higher risk of cancers being missed during screening of dense breasts due to reduced sensitivity of mammography. Automated, deep learning-based prediction of breast density could provide subject-specific risk assessment and flag difficult cases during screening. However, there is a lack of evidence for generalisability across imaging techniques and, importantly, across race. This study used a large, racially diverse dataset with 69,697 mammographic studies comprising 451,642 individual images from 23,057 female participants. A deep learning model was developed for four-class BI-RADS density prediction. A comprehensive performance evaluation assessed the generalisability across two imaging techniques, full-field digital mammography (FFDM) and two-dimensional synthetic (2DS) mammography. A detailed subgroup performance and bias analysis assessed the generalisability across participants' race. Here we show that a model trained on FFDM-only achieves a 4-class BI-RADS classification accuracy of 80.5% (79.7-81.4) on FFDM and 79.4% (78.5-80.2) on unseen 2DS data. When trained on both FFDM and 2DS images, the performance increases to 82.3% (81.4-83.0) and 82.3% (81.3-83.1). Racial subgroup analysis shows unbiased performance across Black, White, and Asian participants, despite a separate analysis confirming that race can be predicted from the images with a high accuracy of 86.7% (86.0-87.4). Deep learning-based breast density prediction generalises across imaging techniques and race. No substantial disparities are found for any subgroup, including races that were never seen during model development, suggesting that density predictions are unbiased.

The Role of Local Angiotensin II/Angiotensin Type 1-receptor Mechanisms in Adipose Tissue Dysfunction to Promote Pancreatic Cancer.

Obesity and adipose tissue dysfunction are important risk factors for pancreatic cancer. Pancreatic cancer is one of the most lethal cancers globally. The renin-angiotensin system (RAS) is expressed in many tissues, including adipose tissue. Dysregulation of angiotensin II and angiotensin II receptors in adipose tissue through the activation of different signaling pathways leads to adipose tissue dysfunction, including insulin resistance, adipose tissue inflammation, adipocytokines secretion, and metabolic alterations. The pathogenesis of pancreatic cancer remains uncertain. However, there is evidence that dysregulation of local angiotensin II in adipose tissue that occurs in association with obesity is, in part, responsible for the initiation and progression of pancreatic cancer. Due to the role of local angiotensin II in the dysfunction of adipose tissue, angiotensin receptor blockers may be considered a new therapeutic strategy in the amelioration of the complications related to adipose tissue dysfunction and prevention of pancreatic cancer. This review aims to consider the biological roles of local angiotensin II and angiotensin II receptors in adipose tissue dysfunction to promote pancreatic cancer progression with a focus on adipose tissue inflammation and metabolic reprogramming.

Analysis of differences in intestinal flora associated with different BMI status in colorectal cancer patients

BackgroundOverweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status.MethodA total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5–23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora.ResultThere was no significant difference in α diversity and β diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated.ConclusionsThe richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this.

Epidemiology of Keratinocyte Skin Cancer with a Focus on Cutaneous Squamous Cell Carcinoma

Keratinocyte skin cancer, consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is by far the most common cancer in white-skinned populations, with rapid increases over the last 50 years. While the age-standardized incidence rates increase worldwide, the age-standardized mortality rates are variable. The incidence rates of keratinocyte skin cancer are much higher compared to those of melanoma, and are largely attributed to the raising exposure to ultraviolet (UV) radiation, the most important causal risk factor for skin cancer. Whereas the development of BCC is mainly due to intense UV exposure during childhood and adolescence, the development of SCC is related to chronic, cumulative UV exposure over decades. Although mortality rates are relatively low, SCC is an increasing problem for healthcare services, significantly causing morbidity, especially in older age groups. This review reports on the epidemiology of keratinocyte skin cancer, with a focus on SCC, in Australia, the United States, and the north of Europe, with an outlook on further challenges health systems will be confronted with in the next 20 years.

The global, regional, and national disease burden of breast cancer attributable to tobacco from 1990 to 2019: a global burden of disease study

ObjectiveTobacco has been identified as a significant contributory element to the development of breast cancer. Our objective was to evaluate the spatiotemporal trends of tobacco-related breast cancer at the global, regional, and national scales during 1990–2019.MethodsWe extracted data on mortality, disability adjusted of life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) from the Global Burden of Disease (GBD) study 2019. Estimated annual percentage change (EAPC) was computed to assess the temporal change in ASDR and ASMR.ResultsIn 2019, the deaths and DALYs attributed to tobacco-related breast cancer were estimated to be 35,439 (95% UI: 22,179–48,119) and 1,060,590 (95% UI: 622,550–1,462,580), respectively. These figures accounted for 5.1% and 5.2% of the total burden of breast cancer. ASMR and ASDR increased in low SDI regions, remained stable in low-middle and middle SDI regions and declined in high and high-middle SDI regions. The burden of breast cancer attributable to tobacco varied notably among regions and nations. Oceania, Southern Latin America, and Central Europe were the GBD regions with the highest number of ASMR and DALYs. There was a positive relationship between age-standardized rate and SDI value in 2019 across 204 nations or territories. A negative association was observed between the EAPC in ASMR or ASDR and the human development index (HDI) in 2019 (R = -0.55, p < 0.01 for ASMR; R = -0.56, p < 0.01 for ASDR).ConclusionTobacco is one important and modifiable risk factor for breast cancer. The heterogeneity in both the spatial and temporal distribution can be attributed to factors such as aging, population growth, and SDI. These findings substantiate the necessity of expediting the enforcement of tobacco-free legislation in order to safeguard populations from the detrimental effects of tobacco.

Risk of ovarian cancer in women using ovarian induction protocols for infertility treatment.

Abstract: Cancer is rapidly becoming a major cause of morbidity and mortality worldwide, &amp; Infertility has been found to be an important risk factor for ovarian cancer. However, the association between infertility drugs and ovarian cancer needs to be addressed with consideration of other factors such as age, body mass index, parity, genetic factors (i.e. family history for ovarian cancer), and etiology of the infertility, along with longer followup times Aim of the study:To rule out or to prove that; the ovulation induction in infertility treatments and can cause ovarian cancer . Design: Retrospective randomized study Setting: Data were obtained from the patient records of those who were diagnosed as ovarian problem, which indicate surgical intervention, at lamis hospital for infertility &amp; Gyn. Misurata -libya. From January 1, 2017 to December 31, 2023. (seven years). Our study contained 110 patients operated with ovarian tumors &amp; 3608 patients treated for infertility by ovulation induction drugs &amp; icsi . Results: The age range of patients with ovarian tumors in our study was from 24 to 72 years, and the highest incidence of ovarian tumors was seen between 46 to 60 years. Most of the patients were at postmenopaus. More than half of the patient with ovarian pathology (58.2%) were multiparous; while nulliparous &amp; patients delivered up to three kids were 8.2% &amp; 33.6% consecutively. The main complain that the patient with ovarian pathology presented with abnormal vaginal bleeding (38.2%) ,lower abdominal pain (26.4%), abnormal vaginal discharge (23.6%) &amp; pelvic mass (21.8%), Some patients were with more than one complains. Only two patient out of 110 included at this study , received ovulation induction drugs (1.8%), while 98.2% of patient with ovarian pathology they never use any drugs for ovarian stimulation. Out of (110) patient there 38 patient were their diagnosis confirmed by histopathology as ovarian cancer of different types, tow patients were received ovulation induction drugs. Only one of them with history of icsi &amp; ovum retrieval (1/3608) I.e. 0.027%, she also had family history of breast cancer.(3608 are the number of cases done ovum retrieval for icsi at lamis infertility clinic at the period from January 2017 up to December 2023.) Conclusions: Although ,the question of whether ovarian stimulation increases the incidence of ovarian cancer, as an independent factor remains unanswered , We confirmed that ovulation induction drugs as treatment of infertility &amp; ovum retrieval for icsi are not a risk factors for ovarian cancer, and we observed no increase incidence of ovarian cancer , Further larger studies are recommended to confirm such findings

Evaluation of the Mechanisms Involved in the Development of Bladder Toxicity following Exposure to Occupational Bladder Cancer Causative Chemicals Using DNA Adductome Analysis.

Occupational exposure to aromatic amines (AAs) is an important risk factor for urinary bladder cancer. This study aimed to evaluate the toxicity of AAs and analyze the carcinogenic mechanisms in rat bladder by comprehensive analysis of DNA adducts (DNA adductome). DNA was extracted from the bladder epithelia of rats treated with AAs, including acetoacet-o-toluidine (AAOT) and o-toluidine (OTD), and adductome analysis was performed. Principal component analysis-discriminant analysis revealed that OTD and AAOT observed in urinary bladder hyperplasia could be clearly separated from the controls and other AAs. After confirming the intensity of each adduct, four adducts were screened as having characteristics of the OTD/AAOT treatment. Comparing with the in-house DNA adduct database, three of four candidates were identified as oxidative DNA adducts, including 8-OH-dG, based on mass fragmentation together with high-resolution accurate mass (HRAM) spectrometry data. Therefore, findings suggested that oxidative stress may be involved in the toxicity of rat bladder epithelium exposed to AAs. Consequently, the administration of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, in six-week-old rats fed with 0.6% OTD in their diet resulted in simple hyperplastic lesions in the bladder that were suppressed by apocynin. The labeling indices of Ki67, γ-H2AX, and 8-OHdG were significantly decreased in an apocynin concentration-dependent manner. These findings indicate that oxidative stress may have contributed to the development of urinary cancer induced by OTD.

Contribution to the study of "smoking and radon" interaction in the lung cancer development across the Republic of Moldova

Introduction. The most important risk factors for lung cancer are the tobacco smoking and residential radon exposure. The study of the interaction of smoking x radon as trigger factor for lung cancer morbidity in the Republic of Moldova was carried out.&#x0D; Material and methods. Data on tobacco smoking prevalence of the national study STEPS 2021, lung cancer morbidity data of 2012-2020 and data of radon measurements using RADTRAK2 during 2018-2021 were used. Data processing tools included summary statistics and cluster analysis.&#x0D; Results. The distribution of high radon values, the number of smokers and the lung cancer morbidity is uneven throughout the country. The formation of higher cluster combining all variables has proceeded by the formation of two clusters: 1. lung cancer incidence, lung cancer prevalence, number of total tobacco smokers, number of male smokers, number of female smokers, and number of urban smokers, 2. radon concentration and number of rural smokers.&#x0D; Conclusions. Study results demonstrate the leading role of tobacco smoking on morbidity among the adult population, regardless of gender in an urban environment with a rather low concentration of radon, and at the same time indicate the cumulative effect of smoking and increased radon concentration in rural areas due to the construction features of houses and lifestyle.

Abstract B133: Disparities in risk factors for nonalcoholic fatty liver disease (NAFLD) among a racially and ethnically diverse cohort

Abstract Background NAFLD has become the leading cause of chronic liver disease and is an important risk factor for liver cancer. About 25% of the U.S. adult population has NAFLD, with prevalence up to 70% among those with type 2 diabetes. Racial and ethnic disparities in NAFLD show Asian and Hispanic Americans at greater risk. Yet, few studies have examined risk factors and the magnitude of influence of these risk factors for NAFLD in racially and ethnically diverse populations. Methods This cohort included patients ≥ 18 years old who had at least two in-person visits at least one year apart between 2000 and 2017 at Kaiser Permanente Hawai`i, a large, integrated healthcare system. We excluded those who had NAFLD diagnosis at baseline (i.e., first year after the first in-person visit from 2000-2017). From the electronic medical record, we obtained data on sociodemographic (age, sex, race, ethnicity) and behavioral (tobacco use, care utilization) characteristics. We also extracted Current Procedural Terminology codes, International Classification of Diseases (ICD)-9 and -10 codes, prescription orders, vital signs, and laboratory results. We used small-area neighborhood data from the Hawaii Neighborhoods Data System. We ran sequential Cox regression models with outcome of incident NAFLD with age as the time-scale, underlying stratification by baseline year and decile of number of outpatient and ED encounters, and clustering by census tract. We added in variables one-by-one based on the order of influence. This was calculated as the percent difference in effect separately for: 1) sex (men compared to women) and 2) for each race and ethnicity group (compared to non-Hispanic White) from the base model when adding in each covariate separately. Results Of 373,032 patients followed for a median of 5.6 years, 8,994 had a diagnosis of incident NAFLD (2.4%). Variables associated with NAFLD and disparities by sex or race/ethnicity included having hypertension, high triglycerides, lower HDL, smoking, diabetes, overweight or obese body mass index (BMI), limited English proficiency, history of smoking, chronic hepatitis C, or low neighborhood SES. High triglycerides (triglycerides ≥150 mg/dL) had a substantial impact on NAFLD risk by sex; when high triglycerides were accounted for, risk among men compared to women changed from higher (HR=1.28; 95% CI:1.16-1.40) to lower (HR=0.74; 0.60-0.91) risk of NAFLD. Risk factors with the greatest impact on NAFLD risk differed across racial/ethnic groups. Among American Indian/Alaska Native and Hispanic adults, chronic hepatitis C virus infection had the greatest impact on NAFLD risk; among Asian American and Native Hawaiian/Pacific Islander adults, it was diabetes mellitus; and among adults with multiple races or ethnicities, it was BMI. Discussion Our analyses show NAFLD risk factors differ by sex and by race and ethnicity. To reduce NAFLD disparities targeted interventions should address the risk factors that are most salient for each of these groups. Citation Format: Janet N. Chu, Mindy C. DeRouen, Alison J. Canchola, Aly Cortella, Pushkar P. Inamdar, Yihe G. Daida, Scarlett L. Gomez, Hashem El-Serag, Salma Shariff-Marco. Disparities in risk factors for nonalcoholic fatty liver disease (NAFLD) among a racially and ethnically diverse cohort [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B133.

Repeated radon exposure induced epithelial-mesenchymal transition-like transformation via disruption of p53-dependent mitochondrial function.

As a human carcinogen, radon and its progeny are the second most important risk factor for lung cancer after smoking. The tumor suppressor gene, p53, is reported to play an important role in the maintenance of mitochondrial function. In this work, we investigated the association between p53 and p53-responsive signaling pathways and radon-induced carcinogenesis. After repeated radon exposure, the malignant characteristics, cell cycle arrest, cell apoptotic rate, adenosine triphosphate (ATP) content, reactive oxygen species (ROS) level, mitochondrial DNA (mtDNA) copy number as well as indicative biomarkers involved in mitochondrial energy metabolism were evaluated in BEAS-2B cells or BALB-c mouse lung tissue. Radon exposure induced epithelial-mesenchymal transition (EMT)-like transformation in BEAS-2B cells, as indicated by increased cell proliferation and migration. Additional mitochondrial alterations, including decreased ATP content, increased ROS levels, mtDNA copy numbers, cell apoptosis, and G2/M cell cycle arrest were observed. Radon exposure caused an energy generation shift from aerobic respiration to glycolysis as reflected by increased expression of TIGAR and p53R2 proteins and decreased expression of SCO2 protein in BEAS-2B cells, and increased expression of p53, SCO2 and TIGAR proteins in mouse lung tissue, respectively. The effects of p53 deficiency on the prevention of mitochondrial dysfunction suggested a protective role of p53 in radon-induced malignant-like features in BEAS-2B cells. Repeated radon exposure induced EMT-like transformation in BEAS-2B cells via disruption of mitochondrial function. Activation of p53 and p53-responsive signaling pathways in BEAS-2B cells and BALB-c mice may confer a protective mechanism for radon-induced lung injury.

A Review of the Effect of Outdoor Polycyclic Aromatic Hydrocarbons on Bladder Cancer

Context: Polycyclic aromatic hydrocarbons (PAHs) are pollutants that are among the most important risk factors for cancer, especially in individuals with underlying diseases. On the other hand, various types of cancers in the vital organs of the body, including the liver, lung, and bladder, and diseases related to the nervous system can be attributed to exposure to this polluting agent. Bladder cancer depends on numerous factors, such as inherited genetic predisposition and external exposure. Polycyclic aromatic hydrocarbons are by-products arising from the incomplete combustion of organic matter. They are found in all environments, such as hospitals, industries, and homes. Objectives: The purpose of this review study was to investigate the epidemiological literature on the side effects of PAHs on bladder cancer and the risk factors related to cancer. Methods: A total of 80 articles according to different databases, namely PubMed, Web of Science, Springer, Cochrane, and ScienceDirect, were retrieved. Then, 38 full-text articles were entered into the analysis process. Finally, 12 articles were selected for this study. Results: The literature review showed that PAH exposure occurs in daily life through exposure to tobacco smoke, consumption of charcoal-smoked meats, and inhalation of air pollutants. The concentration of PAHs is related to the risk of developing bladder cancer during the lifetime of PAHs. Bladder tumors are directly related to exposure to carcinogens. While the exposure to risk factors increases, the risk of developing cancer increases. Risk factors affecting bladder cancer include smoking and occupational and dietary factors. Conclusions: Polycyclic aromatic hydrocarbons are by-products of incomplete combustion of organic matter. They are found in all environments, such as hospitals, industries, and homes, and they can affect the urinary system, cause dysfunction, and eventually cause bladder cancer.