Individual Cancer Risk Research Articles

Association between diabetes status and breast cancer in US adults: findings from the US National Health and Nutrition Examination Survey.

The aim of this study was to investigate the association between diabetes status and the risk of breast cancer among adult Americans, exploring the impact of BMI, age, and race on this relationship. A cross-sectional analysis of 8,249 individuals from the National Health and Nutrition Examination Survey (NHANES) was conducted. Diabetes was categorized as type 2 diabetes and prediabetes, with both conditions diagnosed according to the ADA 2014 guidelines. The association between diabetes status and breast cancer risk was explored using multiple logistic regression analysis. Patients with diabetes had higher odds of breast cancer (OR: 1.51; 95% CI 1.00 to 2.28), Using the two-piecewise linear regression model, it was observed that there is a threshold effect in the risk of breast cancer occurrence at the age of 52 years. Specifically, the risk of breast cancer is relatively low before the age of 52 but increases significantly after this age. This study identified a significant association between diabetes status and breast cancer risk among adult Americans. We also found a threshold effect in breast cancer occurrence at the age of 52. Age was significantly associated with breast cancer risk in both Non-Hispanic White and Non-Hispanic Black individuals. These findings underscore the importance of diabetes management, maintaining a healthy BMI, and age-related risk considerations in reducing breast cancer risk.

The presence of circulating genetically abnormal cells in blood predicts risk of lung cancer in individuals with indeterminate pulmonary nodules

PurposeComputed tomography is the standard method by which pulmonary nodules are detected. Greater than 40% of pulmonary biopsies are not lung cancer and therefore not necessary, suggesting that improved diagnostic tools are needed. The LungLB™ blood test was developed to aid the clinical assessment of indeterminate nodules suspicious for lung cancer. LungLB™ identifies circulating genetically abnormal cells (CGACs) that are present early in lung cancer pathogenesis.MethodsLungLB™ is a 4-color fluorescence in-situ hybridization assay for detecting CGACs from peripheral blood. A prospective correlational study was performed on 151 participants scheduled for a pulmonary nodule biopsy. Mann-Whitney, Fisher’s Exact and Chi-Square tests were used to assess participant demographics and correlation of LungLB™ with biopsy results, and sensitivity and specificity were also evaluated.ResultsParticipants from Mount Sinai Hospital (n = 83) and MD Anderson (n = 68), scheduled for a pulmonary biopsy were enrolled to have a LungLB™ test. Additional clinical variables including smoking history, previous cancer, lesion size, and nodule appearance were also collected. LungLB™ achieved 77% sensitivity and 72% specificity with an AUC of 0.78 for predicting lung cancer in the associated needle biopsy. Multivariate analysis found that clinical and radiological factors commonly used in malignancy prediction models did not impact the test performance. High test performance was observed across all participant characteristics, including clinical categories where other tests perform poorly (Mayo Clinic Model, AUC = 0.52).ConclusionEarly clinical performance of the LungLB™ test supports a role in the discrimination of benign from malignant pulmonary nodules. Extended studies are underway.

Community-generated solutions to cancer inequity: recommendations from transgender, non-binary and intersex people on improving cancer screening and care

ObjectiveTransgender, non-binary and intersex people are less likely to receive appropriate cancer screening for their bodies and have a higher incidence of certain cancers than cisgender people. We aimed to...

A randomized controlled trial evaluating pretest cancer genetics educational video or in-person genetic counseling.

10597 Background: Cancer genetic testing indications are rapidly expanding to determine treatment eligibility for patients with cancer, to identify individual cancer risk as well as to select family members at higher cancer risk when a pathogenic variant (PV) has been identified in the family. Currently, international guidelines recommend that all candidates for genetic testing should have genetic counseling to make an informed decision for genetic testing. However, with the increased demand for genetic testing, innovative ways to deliver pretest information are needed, especially in limited resource settings, where genetic cancer professionals’ availability is scarce. Methods: This is a non-inferiority trial comparing a pretest educational video to in-person genetic counseling. Participants referred for genetic cancer risk assessment at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City were enrolled if they met international cancer genetic testing criteria and did not previously have genetic testing and/or counseling. The primary outcome was the uptake of genetic testing. Secondary outcomes included changes in genetic cancer knowledge, anxiety, and satisfaction using validated tools. Results: A total of 250 participants were included: 124 were randomized to the in-person genetic counseling arm and 126 to the educational video arm. Mean age was 47.9 years (SD 12.7), 86.4% were women, 37.2% had high-school or less and 86.4% had personal history of cancer (70% breast cancer). Overall, test acceptance was 100% in both arms. Cancer genetics knowledge improved in both groups: in-person from. 53 to .74 (diff .20; 95%CI .24-.26; p < 0.05) and video from .51 to .68 (diff .16; 95%CI .20-.12; p < 0.05). However, the in-person arm had a higher post counseling knowledge score (p 0.001). 43.5% and 42% of participants in the in-person and video arms had moderate-severe baseline anxiety. After intervention, both groups had a decrease in anxiety score: in-person from 5.2 to 4.7 (diff .58; 95% CI .09-1.08; p 0.01) and video from 4.9 to 4.1 (diff .75; 95%CI 0.42-1.08; p < 0.05). Both groups were satisfied with genetic services (97.5% and 92.5%, respectively; p 0.34). Conclusions: A pretest educational video was non-inferior regarding genetic testing acceptance. It was also associated with improved genetic cancer knowledge and decreased anxiety levels. These results support the use of educational videos before genetic testing where in-person genetic counseling availability is limited. Clinical trial information: pending .

Effect of polycyclic aromatic hydrocarbons on cancer risk causally mediated via vitamin D levels.

Polycyclic aromatic hydrocarbons (PAHs) widely exist in environmental substrates and are closely related to individual circulating vitamin D levels and tumorigenesis. Therefore, we proposed to evaluate the relationship between PAH exposure, vitamin D, and the risks for 14 cancer types via a causal inference framework underlying the mediation analysis. We evaluated seven urine monohydroxylated PAH (OH-PAH) and serum vitamin D concentrations of 3306 participants from the National Health and Nutrition Examination Survey between the 2013 and 2016 survey cycles and measured PAH concentrations in 150 subjects from the Nanjing cohort. We observed a significant negative dose-response relationship between increased OH-PAH levels and vitamin D deficiency. Each unit increase in ∑OH-PAHs could lead to a decrease in vitamin D levels (βadj = -0.98, Padj = 2.05 × 10-4 ). Body mass index could have interaction effects with ∑OH-PAHs and affect vitamin D levels. Coexposure to naphthalene and fluorene metabolites mutually affected vitamin D levels. Notably, vitamin D could causally mediate the relationship between OH-PAHs and nine types of cancer (e.g., colorectal cancer, liver cancers, etc.). This study first emphasizes the causal cascade of individual OH-PAHs, vitamin D, and cancer risk, providing insights into prevention via the environment.

Monte Carlo-based probabilistic risk assessment for cement workers exposed to heavy metals in cement dust.

This study assessed the carcinogenic and non-carcinogenic health risks of cement plant workers exposed to chromium (Cr), arsenic (As), cadmium (Cd), and lead (Pb) in cement dust using a probabilistic approach. Air samples were collected according to NIOSH 7900 and OSHA ID-121 methods and analyzed by an graphite furnace atomic absorption spectrometer. The EPA inhalation risk assessment model and Monte Carlo simulation were utilized to assess the health risks. Sensitivity analysis was used to determine the influencing parameters on health risk. The average concentrations of As and Pb exceeded the occupational exposure limit (OEL), reaching a maximum of 3.4 and 1.7 times the OEL, respectively, in the cement mill. Individual metals' cancer risk exceeded the 1E-4 threshold in ascending order of Cd < As < Cr. The mean cancer risk of Cr ranged from 835E-4 (in raw mill) to 2870E-4 (in pre-heater and kiln). Except for Cd, the non-cancer risk of metals exceeded the standard (hazard index, HQ = 1) in the ascending order of Pb < As < Cr. The mean HQ of Cr ranged from 162.13 (in raw mill) to 558.73 (in pre-heater and kiln). After adjusting for control factors, the cancer and non-cancer risks remained over the respective recommended levels. Sensitivity analysis revealed that the concentration of Cr was the most influential parameter on both carcinogenic (78.5%) and non-carcinogenic (88.06%) risks. To protect the health of cement factory employees, it is recommended to minimize cement dust emissions, implement job rotation, and use raw materials with low levels of heavy metals.

Association between the Finnish Diabetes Risk Score and cancer in middle-aged and older adults: Involvement of inflammation

BackgroundDiabetes is associated with increased risk of common cancers. However, evidence of cancer risk in individuals with different diabetes risk is still scarce, and the underlying mechanism remains unknown. Therefore, we aimed to evaluate the relationship between the Finnish Diabetes Risk Score (FINDRISC) and risks of cancer incidence and mortality in a prospective study, and to explore whether low-grade inflammation partially mediated the association. MethodsA total of 330,384 participants aged 37 to 73 at baseline from the UK Biobank database was included in this study. The Cox proportional hazards model was used to examine the relationship of the FINDRISC and low-grade inflammation with risks of cancer incidence and mortality. Then, we estimated the contribution of higher FINDRISC to risks of overall and site-specific cancers. In addition, the role of low-grade inflammation in the association between FINDRISC and cancer risks was investigated through mediation analysis. ResultsThe increased FINDRISC was dose-dependently associated with higher incidence and mortality risks of overall cancer and an overwhelming majority of site-specific cancers. The higher FINDRISC was a strong contributor to incidence of eighteen site-specific cancers and mortality of fourteen site-specific cancers, with a population-attributable risk of 8.1 %–39.1 %, 14.2 %–39.7 %, respectively. Additionally, low-grade inflammation mainly mediated the association between the FINDRISC and risks of incidence and mortality of overall cancer, colorectal cancer, etc. ConclusionsOur findings highlighted the higher FINDRISC as critical risk factors of cancer incidence and mortality, partially mediated by low-grade inflammation. Individuals with increased risk of diabetes are also needed to be concerned about cancer prevention.

Beyond the cancer slope factor: Broad application of Bayesian and probabilistic approaches for cancer dose-response assessment

Traditional cancer slope factors derived from linear low-dose extrapolation give little consideration to uncertainties in dose–response model choice, interspecies extrapolation, and human variability. As noted previously by the National Academies, probabilistic methods can address these limitations, but have only been demonstrated in a few case studies. Here, we applied probabilistic approaches for Bayesian Model Averaging (BMA), interspecies extrapolation, and human variability distributions to 255 animal cancer bioassay datasets previously used by governmental agencies. We then derived predictions for both population cancer incidence and individual cancer risk. For model uncertainty, we found that lower confidence limits from BMA and from U.S. Environmental Protection Agency (EPA)’s Benchmark Dose Software (BMDS) correlated highly, with 86% differing by <10-fold. Incorporating other uncertainties and human variability, the lower confidence limits of the probabilistic risk-specific dose (RSD) at 10−6 population incidence were typically 3- to 30-fold lower than traditional slope factors. However, in a small (<7%) number of cases of highly non-linear experimental dose–response, the probabilistic RSDs were >10-fold less stringent. Probabilistic RSDs were also protective of individual risks of 10−4 in >99% of the population. We conclude that implementing Bayesian and probabilistic methods provides a more scientifically rigorous basis for cancer dose–response assessment and thereby improves overall cancer risk characterization.

An Evidence-Based Review of Diabetes Care: History, Types, Relationship to Cancer and Heart Disease, Co-Morbid Factors, and Preventive Measures

Abstract: Diabetes is characterized by hyperglycemia due to the decreased and inadequate levels of insulin in the body, resistance to the effects of insulin, or a combination of both. There are three types of diabetes, however Type 2 disease is the most common followed by Type 1 and gestational diabetes. Most common factors responsible for diabetes are obesity or being overweight, impaired glucose tolerance, insulin resistance, ethnic background, sedentary lifestyle and family history. Because of the increased longevity, it is becoming a disease of the elderly thus contributing to the complexity of managing it in the ageing population. Diabetes also has implications to cancer and heart disease. Some studies have shown increased cancer risk in prediabetic and diabetic individuals. A recent major study draws firm conclusion that diabetes promotes a person’s risk of developing different types of cancer. The occurrence and mortality of cancer types, e.g., pancreas, liver, colorectal, breast, endometrial, and bladder cancers may produce a modest rise in diabetics. Women with diabetes are 27% likelier to develop cancer compared to healthy women. On the other hand only 19% more men with diabetes are likely to develop cancer when compared to healthy men. Preventive measures such as proper diet, physical activity, weight management, smoking cessation, and controlling obesity may improve outcomes of Type 2 diabetes (T2D) and some forms of cancer. Developing awareness of the genetic association relationship between T2D and coronary heart disease has begun to provide the potential for better prevention and treatment of both disorders. Significant preventive measures for diabetes include – consumption of nutrients such as vitamin D, nuts, minerals chromium, and magnesium, controlling weight, hypertension, plant foods and a Mediterranean plant-based diet along with increased exercise.

Exploring genetic loci of type 2 diabetes and cancer: a review.

Diabetes and cancer are two heterogenous diseases which are rapidly increasing in prevalence globally. A link between these two non-communicable diseases was first identified over 100 years ago; however, recent epidemiological studies and advances in genomic research have provided greater insight into the association between diabetes and cancer. Epidemiological studies have suggested that individuals with diabetes have an increased risk of several types of cancer (including liver, pancreas, colorectal, breast, and endometrial) and an increased risk of cancer mortality. However, this increased risk is not observed in all cancers, for example, there is a reduced risk of prostate cancer in individuals with diabetes. It has also been observed that cancer patients have an increased risk of developing diabetes, highlighting that the relationship between these diseases is not straightforward. Evidence of a shared genetic aetiology along with numerous lifestyle and clinical factors have made it challenging to establish if the relationship between the two diseases is causal or a result of confounding factors. This review takes a pan-cancer approach to highlight the complexities of the interactions between type 2 diabetes and cancer development, indicating where advances in genomic research have enabled a greater insight into these two diseases.

Risk of anorectal cancer in patients with Crohn's disease and perianal fistula: a nationwide Danish cohort study.

Patients with Crohn's disease (CD) often suffer from perianal fistulizing disease. Their risk of anorectal cancer remains uncertain. We aimed to examine the long-term risk of anorectal cancer in a population-based cohort of CD patients with anorectal fistula. Our study population covered all individuals (n = 7 987 520) aged 15+ years living in Denmark from 1978 to 2018. We identified all patients with CD and anorectal fistula in the Danish National Patient Register (NPR) and 50 matched noninflammatory bowel disease (IBD) individuals from the general population. Using Cox regression analyses, we examined the risk of anorectal cancer in CD fistula patients versus non-IBD individuals. All patients with CD were identified using codes from the International Classification of Diseases and their data extracted from the NPR. The main outcome measure was cases of anorectal cancer. A total of 2786 CD patients with anorectal fistula and 139 300 non-IBD individuals were followed for 1 553 917 person-years. During follow-up, anorectal cancer was observed in 19 CD patients (0.68%) and 340 non-IBD individuals (0.24%), corresponding to a 2.9-fold increased hazard ratio (HR) of anorectal cancer in CD fistula patients (95% CI 1.80-4.53), with a particularly high risk of anal cancer (HR 15.13, 95% CI 6.88-33.31) and a mean time from CD fistula diagnosis to anorectal cancer of 6.7 (SD 6.5) years. The risk was slightly higher in women than men and had no apparent relation to treatment with tumour necrosis factor-α inhibitors. Sensitivity analyses using CD nonfistula patients for comparison revealed similar results. Individual data on smoking and infection with human papilloma virus were not available. Patients with CD and anorectal fistula have a three-fold increased risk of anorectal cancer compared with the general population. The number needed to surveil to detect one case of anorectal cancer in this patient population was 2160 patients per year in patients with long-standing fistula (>6 years).

The association between genetically elevated polyunsaturated fatty acids and risk of cancer

The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain. Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures. Genetically elevated PUFA desaturase activity was associated (P<0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR=1.00 [95% CI: 0.99-1.01]; Pheterogeneity=0.25), urinary system cancers (1.03 [0.99-1.06], Pheterogeneity=0.51), nervous system cancers (0.99 [0.95-1.03], Pheterogeneity=0.92) or blood cancers (1.01 [0.98-1.04], Pheterogeneity=0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P<0.0006) with increased risk of inflammatory bowel disease but not bleeding. The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease. Cancer Resesrch UK (C52724/A20138, C18281/A19169). UK Medical Research Council (MR/P014054/1). National Institute for Health Research (NIHR202411). UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4). National Cancer Institute (R00 CA215360). National Institutes of Health (U01 CA164973, R01 CA60987, R01 CA72520, U01 CA74806, R01 CA55874, U01 CA164973 and U01 CA164973).

Abstract LB142: Metabolically defined body size phenotypes in relation to subsequent colorectal cancer risk

Abstract Overweight and obesity have been linked to increased risk of several diseases, including colorectal cancer, but the underlying mechanisms are not fully known. An earlier study analyzed metabolically defined body size phenotypes in relation to colorectal cancer risk, using combinations of C-peptide (a marker of insulin resistance) and body mass index (BMI). Higher serum C-peptide concentrations were associated with higher colorectal cancer risk in both overweight and normal weight individuals compared to individuals with low levels of C-peptide and normal weight. The aim of the present study was to see if these results could be replicated and to further explore the role of metabolism and body size phenotypes in colorectal cancer subtypes. We conducted a nested case-control study of 1010 individuals with colorectal cancer and 1010 individually matched (age, sex, cohort, year of blood sampling and data collection, number of freeze-thaw cycles of plasma samples and fasting status at blood sampling) control participants from the population-based Northern Sweden Health and Disease Study. The blood samples and data used in our analyses were collected at a mean of 9.7 years prior to case diagnosis. Participants were categorized as (1) metabolically healthy/normal weight (BMI &amp;lt; 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI &amp;lt; 25 kg/m2), or (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2), where metabolically healthy was defined as C-peptide in the lowest tertile, as in the previous study. We used multivariable conditional logistic regression to calculate odds ratios and confidence intervals and adjusted for tobacco smoking, recreational physical activity and alcohol consumption as potential confounders. In our preliminary results, metabolically unhealthy/overweight individuals had a significantly higher risk of developing colorectal cancer compared to metabolically healthy/normal weight individuals (adjusted odds ratio =1.44, 95% CI 1.13-1.85). The odds ratio for metabolically unhealthy/normal weight individuals was 1.23 (95% CI 0.92-1.65) and for metabolically healthy/overweight individuals 1.23 (95% CI 0.89-1.70). These results support the potential of a more nuanced analysis of metabolism and body size to better understand their etiological contribution to colorectal cancer development. To gain more knowledge about how the role of metabolism and body size might differ between tumor subtypes, we will also analyze body size phenotypes in relation to subtypes of colorectal cancer based on anatomical tumor site, KRAS and BRAF mutations and microsatellite instability status of the tumor. Citation Format: Linda Vidman, Simon Knekta, Björn Gylling, Carl Zingmark, Anna Löfgren-Burström, Richard Palmqvist, Sophia Harlid, Bethany Van Guelpen. Metabolically defined body size phenotypes in relation to subsequent colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB142.

Probabilistic health risk assessment of occupational exposure to BTEX in a paint manufacturing plant using Monte-Carlo simulation

This study assessed the health risks of paint industry workers exposed to benzene, toluene, ethylbenzene, and xylene (BTEX) compounds using a probabilistic approach. Air samples were collected using charcoal tubes according to the NIOSH 1501 method and analyzed by a GC-FID. The EPA risk assessment model was used to assess the lifetime carcinogenic and non-carcinogenic risks posed by BTEX. A sensitivity analysis was performed to clarify the influence of input parameters on the health risks. In the paint production, paint packing, and thinner packing workshops, the concentration of at least two aromatic compounds exceeded the occupational exposure limit. Ethylbenzene posed greater carcinogenic risks than benzene. The individual and total cancer risk of benzene and ethylbenzene exceeded the 1E–4 level, indicating a definite cancer risk in all workshops of the factory. The mean of total non-cancer risk exceeded the standard (hazard index = 1) in all workshops with xylene as the most contributing aromatics in non-cancer risk. Putty production (428.5), thinner packing (340.79), and spray paint packing (148.45) were the workshops with the greatest hazard index. Sensitivity analysis indicated that the concentration of ethylbenzene and xylene contributed the most to cancer (73.0%) and non-cancer (87.8%) risks. These findings can help managers better understand BTEX-related risks faced by paint manufacturing workers and the need to control BTEX contamination to reduce health risks below the standard in paint industry.

MP77-05 PROSTATE CANCER TRENDS AMONG INDIVIDUAL ASIAN AND PACIFIC ISLANDERS (AAPI) POPULATIONS IN HAWAII

You have accessJournal of UrologyCME1 Apr 2023MP77-05 PROSTATE CANCER TRENDS AMONG INDIVIDUAL ASIAN AND PACIFIC ISLANDERS (AAPI) POPULATIONS IN HAWAII Lauren Muramoto, Brenda Hernandez, and Tom Feng Lauren MuramotoLauren Muramoto More articles by this author , Brenda HernandezBrenda Hernandez More articles by this author , and Tom FengTom Feng More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Asians and Pacific Islanders (AAPIs) are often grouped together as a single racial demographic when reporting prostate cancer trends despite the heterogeneity within this community. Hawaii’s multi-ethnic community poses a unique environment to study the epidemiology of prostate cancer. We examine differences in incidence and mortality of prostate cancer among AAPIs within Hawaii. METHODS: Data were obtained from the Hawaii Tumor Registry Cancer at a Glance 2014-2018 report. All reported rates were age adjusted per 100,000 to the 2000 US standard population. Differences in incidence and mortality rates were compared among the major AAPI groups: Chinese, Filipino, Japanese, and Native Hawaiian. RESULTS: Prostate cancer is the most common cancer diagnosed in men in Hawaii with an incidence of 22.8% and responsible for 9.6% of cancer related deaths from 2014-2018. Incidence rates among the four major AAPI groups were not statistically different (Figure 1a). Despite this, mortality rates were significantly lower in Chinese (5.5 per 100,000) and Japanese (8.7) compared to Filipinos (16.4) and native Hawaiians (21.6, p<0.05, Figure 1b). Native Hawaiians had the lowest incidence rate (80.2) but had the highest mortality rates among Asians (21.6 per 100,000). Filipinos, despite having similar incidence as Chinese and Japanese, had much higher mortality rates (p<0.05) and the highest proportion of advanced prostate cancer 34.7% at diagnosis. CONCLUSIONS: Hawaii’s diversity plays an important role in reporting cancer incidence and mortality among AAPI. Differences could be related to access to care, genetics, education level or lifestyle related exposures. These data support the need to disaggregate AAPI subpopulations to better understand individual prostate cancer risk profiles. Further research is needed to determine these differing factors among AAPI ethnicities affect prostate cancer risk and outcomes. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1103 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lauren Muramoto More articles by this author Brenda Hernandez More articles by this author Tom Feng More articles by this author Expand All Advertisement PDF downloadLoading ...

Risk of pancreatic cancer in individuals with celiac disease in the United States: A population-based matched cohort study

Celiac disease (CD) has been associated with gastrointestinal malignancies. However, the magnitude of the risk of pancreatic cancer (PC) associated with CD is much less clear, and risks have not been estimated from large populations. To assess the risk of PC in CD patients. We conducted a population-based, multicenter, propensity score-matched cohort study with consecutive patients diagnosed with CD using the TriNeTx research network platform. We examined the incidence of PC in patients with CD compared with a matched cohort of patients without CD (non-CD, controls). Each patient in the main group (CD) was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. The incidence of PC was estimated using a Cox proportional hazards model with a hazard ratio (HR) and 95% confidence interval (CI). A total of 389980 patients were included in this study. Among them, 155877 patients had a diagnosis of CD, and the remaining 234103 individuals without CD were considered a control cohort. The mean duration of follow-up for patients in the CD and control cohorts was 5.8 ± 1.8 and 5.9 ± 1.1 years, respectively. During the follow-up, 309 patients with CD developed PC, whereas 240 patients developed PC in the control group (HR = 1.29; 95%CI: 1.09-1.53). In the secondary analyses in the first year after diagnosis of CD, patients with CD were at a significant increase in risk for PC; 151 patients with CD had an incidence of PC compared with 96 incidences of PC among the patients in the non-CD control group (HR = 1.56; 95%CI: 1.20-2.01) and sensitivity analysis showed similar magnitude to the one generated in the primary and secondary analysis. Patients with CD are at increased risk of PC. Risk elevation persists beyond the first year after diagnosis to reference individuals without CD from the general population.

Shotgun Metagenomics of Gastric Biopsies Reveals Compositional and Functional Microbiome Shifts in High- and Low-Gastric-Cancer-Risk Populations from Colombia, South America

ABSTRACT Along with Helicobacter pylori infection, the gastric microbiota is hypothesized to modulate stomach cancer risk in susceptible individuals. Whole metagenomic shotgun sequencing (WMS) is a sequencing approach to characterize the microbiome with advantages over traditional culture and 16S rRNA sequencing including identification of bacterial and non-bacterial taxa, species/strain resolution, and functional characterization of the microbiota. In this study, we used WMS to survey the microbiome in extracted DNA from antral gastric biopsy samples from Colombian patients residing in the high-risk gastric cancer town Túquerres (n = 10, H. pylori-positive = 7) and low-risk town of Tumaco (n = 10, H. pylori-positive = 6). Kraken2/Bracken was used for taxonomic classification and abundance. Functional gene profiles were inferred by InterProScan and KEGG analysis of assembled contigs and gene annotation. The most abundant taxa represented bacteria, non-human eukaryota, and viral genera found in skin, oral, food, and plant/soil environments including Staphylococus, Streptococcus, Bacillus, Aspergillus, and Siphoviridae. H. pylori was the predominant taxa present in H. pylori-positive samples. Beta diversity was significantly different based on H. pylori-status, risk group, and sex. WMS detected more bacterial taxa than 16S rRNA sequencing and aerobic, anaerobic, and microaerobic culture performed on the same gastric biopsy samples. WMS identified significant differences in functional profiles found between H. pylori-status, but not risk or sex groups. H. pylori-positive samples were significantly enriched for H. pylori-specific genes including virulence factors such as vacA, cagA, and urease, while carbohydrate and amino acid metabolism genes were enriched in H. pylori-negative samples. This study shows WMS has the potential to characterize the taxonomy and function of the gastric microbiome as risk factors for H. pylori-associated gastric disease. Future studies will be needed to compare and validate WMS versus traditional culture and 16S rRNA sequencing approaches for characterization of the gastric microbiome.

A common genetic variation in GZMB may associate with cancer risk in patients with Lynch syndrome.

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is a common genetic predisposition to cancer due to germline mutations in genes affecting DNA mismatch repair. Due to mismatch repair deficiency, developing tumors are characterized by microsatellite instability (MSI-H), high frequency of expressed neoantigens and good clinical response to immune checkpoint inhibitors. Granzyme B (GrB) is the most abundant serine protease in the granules of cytotoxic T-cells and natural killer cells, mediating anti-tumor immunity. However, recent results confirm a diverse range of physiological functions of GrB including that in extracellular matrix remodelling, inflammation and fibrosis. In the present study, our aim was to investigate whether a frequent genetic variation of GZMB, the gene encoding GrB, constituted by three missense single nucleotide polymorphisms (rs2236338, rs11539752 and rs8192917) has any association with cancer risk in individuals with LS. In silico analysis and genotype calls from whole exome sequencing data in the Hungarian population confirmed that these SNPs are closely linked. Genotyping results of rs8192917 on a cohort of 145 individuals with LS demonstrated an association of the CC genotype with lower cancer risk. In silico prediction proposed likely GrB cleavage sites in a high proportion of shared neontigens in MSI-H tumors. Our results propose the CC genotype of rs8192917 as a potential disease-modifying genetic factor in LS.

Risk and incidence of breast cancer in transgender individuals: a systematic review and meta-analysis.

The risk of developing breast cancer in transgender individuals [male-to-female (MtF) or female-to-male (FtM)] is still inadequately quantified. We aimed to evaluate the impact of breast cancer in this population. We conducted a systematic literature search and review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines through the PUBMED and SCOPUS databases. We identified six cohort studies (for both populations) plus 35 case reports. Incidence and breast cancer risk quantification were the main outcomes considered. FtM individuals had a higher risk of developing breast cancer in comparison to cisgender men [standardized incidence ratio (SIR) = 63.4; 95% confidence interval (CI), 32.2-124.9] but a lower risk than cisgender women (SIR = 0.42; 95% CI, 0.07-2.41). Similarly, MtF individuals were at higher risk of developing breast cancer in comparison to cisgender men (SIR = 22.5; 95% CI, 5.54-91.8) and at lower risk than cisgender women (SIR = 0.30; 95% CI, 0.22-0.42). In this systematic study and meta-analysis, we identified that FtM and MtF individuals are at substantially higher risk of developing breast cancer in comparison to cisgender men, though at lower risk than cisgender women. These individuals, in the absence of defined guidelines for breast cancer prevention, should periodically undergo breast or chest examinations.

Internet-based assessment tools for predicting colorectal cancer risk: How do they communicate individualized risk to the young adult?

72 Background: Online prediction tools for cancer risk can inform individuals about their risk and potentially encourage adoption of risk-modifying health behavior. The Colorectal Cancer Risk Assessment Tool (CCRAT) is an interactive tool developed by the National Cancer Institute for estimating colorectal cancer (CRC) risk for individuals between the ages of 45 and 85 without high risk predisposing conditions. Given the rising incidence of CRC among young adults under age 50, we aimed to investigate the performance of CCRAT in estimating their CRC risk. Methods: An institutional protocol prospectively enrolled 563 patients newly diagnosed with non-hereditary CRC and administered a health behavior questionnaire at baseline. Self-reported demographics, diet and physical activity, medication use, and family history were extracted and entered into the CCRAT ( https://ccrisktool.cancer.gov/calculator.html ) to calculate their predicted 5-year and lifetime CRC risks. Health behaviors and the predicted CRC risks in reference to the population average were compared among three groups: youngest- (aged 18-44, N = 276, 49%), young- (aged 45-50, N = 178, 32%), and older-onset (aged &gt; 50, N = 109; 19%). Results: The patient groups did not significantly differ in gender or in family history of CRC, but the youngest group had significantly more non-White patients (27, 22, vs. 19%; p = 0.008) and distal tumors (80, 76 and 65%; p = 0.05). The youngest and young groups had a higher prevalence of morbid obesity (18 and 15% vs. 12%; p = 0.002) and active smokers (6 and 8% vs. 3%; p = 0.005). There were no significant differences in vegetable intake, moderate exercise, NSAID use, or female hormone use. The 5-year CRC risk was correctly predicted as “higher than average population” for a significantly smaller proportion of the youngest (42%) and young (45%) patients, when compared to their older counterpart (71%; p &lt; 0.001). Similarly, the tool communicated “higher than average” lifetime risk for CRC in only 56 and 60% of the youngest and young patients, but 72% of the older ones (p = 0.021). Conclusions: The existing risk prediction tool inadequately communicated CRC risk for adults younger than 50 years of age. Risk factors underlying young-onset CRC likely differ from and extend beyond those as currently assessed. New tools capturing age-specific risk factors are needed to accurately communicate individualized risk and potentially motivate risk-modifying lifestyles.