Allometric fat mass index and alanine aminotransferase attenuate the associations of platelet parameters with lung cancer risk.

We have previously shown that body mass index attenuates a positive association of platelet count (PLT) and inverse of mean platelet volume (MPV) with lung cancer risk in men. It is unclear whether fat mass, lean mass, or liver function tests (LFTs) show similar attenuations. Using bioelectrical impedance measurements (UK Biobank cohort) and multivariable Cox proportional hazards models, we examined the associations of allometric fat-mass index (AFI, fat mass adjusted for height), allometric lean-mass index (ALI, fat-free mass adjusted for height and fat mass), and LFTs with lung cancer risk and their multiplicative and additive interactions with platelet parameters. Based on 1573 lung cancer cases in men and 1473 in women with body composition measurements (1541 in men; 1428 in women with biomarker measurements), AFI in women, ALI in both sexes, alanine aminotransferase (ALT) and total bilirubin in men were inversely associated, while gamma-glutamyl transferase in men and alkaline phosphatase in both sexes were positively associated with lung cancer risk. Only AFI and ALT interacted inversely with PLT and positively with MPV in men. The attenuation of the associations of platelet parameters with lung cancer risk by high-AFI and high-ALT in men suggests that adiposity-related factors hinder lung-cancer-related platelet associations.

Defining a parameter to select the best radiotherapy technique in patients with right breast cancer after conservative surgery: Evaluation of high doses and risk of radio-induced second tumors to the ipsilateral lung.

PURPOSE: In the adjuvant right breast radiation therapy, after breast-conserving surgery, we wanted to look for a parameter that would help in the choice between the 3D-CRT or VMAT techniques, considering the risk of pneumonia to the ipsilateral lung (IL) linked to high doses. We also investigated the risk of second tumors in the IL related to the VMAT low doses. METHODS: We examined twenty-five 3D-CRT and thirty-five VMAT technique plans, between September 2022 and September 2023. We collected the MAximum Thickness of Ipsilateal Lung (MATIL) included between lateral and medial target borders for evaluating the risk of pneumonia due to the high dose (V20Gy), finally we calculated the Excess of Absolute Risk related to the second tumor risk due to the low dose. RESULTS: VMAT technique showed a better dose conformity than 3D-CRT. We detected a linear relationship between the V20Gy and MATIL of the IL only for the 3D-CRT technique; over a threshold value of MATIL the 3D-CRT is disadvantaged compared to the VMAT in terms of the risk of toxicity to the IL. We calculated that for every Gy more in average dose, a 12 % increase in the risk of induced cancer is expected. CONCLUSIONS: In the adjuvant right breast RT, the MATIL is a good surrogate parameter to predict the need to use a VMAT technique to limit high doses to IL. VMAT technique, according to the IL second tumor estimated risk, seems justified.

Lung cancer and obesity: A contentious relationship (Review).

The global obesity epidemic, attributed to sedentary lifestyles, unhealthy diets, genetics and environmental factors, has led to over 1.9 billion adults being classified as overweight and 650 million living with obesity. Despite advancements in early detection and treatment, lung cancer prognosis remains poor due to late diagnoses and limited therapies. The obesity paradox challenges conventional thinking by suggesting that individuals with obesity and certain diseases, including cancer, may have an improved prognosis compared with their counterparts of a normal weight. This observation has prompted investigations to understand protective mechanisms, including potentially favorable adipokine secretion and metabolic reserves that contribute to tolerating cancer treatments. However, understanding the association between obesity and lung cancer is complex. While smoking is the primary risk factor of lung cancer, obesity may independently impact lung cancer risk, particularly in non­smokers. Adipose tissue dysfunction, including low­grade chronic inflammation, and hormonal changes contribute to lung cancer development and progression. Obesity­related factors may also influence treatment responses and survival outcomes in patients with lung cancer. The impact of obesity on treatment modalities such as chemotherapy, radiotherapy and surgery is still under investigation. Challenges in managing patients with obesity and cancer include increased surgical complexity, higher rates of postoperative complications and limited treatment options due to comorbidities. Targeted interventions aimed at reducing obesity prevalence and promoting healthy lifestyles are crucial for lung cancer prevention. The impact of obesity on lung cancer is multifaceted and requires further research to elucidate the underlying mechanisms and develop personalized interventions for prevention and treatment.

Pesticides and prostate cancer incidence and mortality: An environment-wide association study.

BACKGROUND: Prostate cancer is the most common cancer among men in the United States, yet modifiable risk factors remain elusive. In this study, the authors investigated the potential role of agricultural pesticide exposure in prostate cancer incidence and mortality. METHODS: For this environment-wide association study (EWAS), linear regression was used to analyze county-level associations between the annual use of 295 distinct pesticides (measured in kg per county) and prostate cancer incidence and mortality rates in the contiguous United States. Data were analyzed in two cohorts: 1997-2001 pesticide use with 2011-2015 outcomes (discovery) and 2002-2006 use with 2016-2020 outcomes (replication). The reported effect sizes highlight how a 1-standard-deviation increase in log-transformed pesticide use (kg per county) corresponds to changes in incidence. Analyses were adjusted for county-level demographics, agricultural data, and multiple testing. RESULTS: Twenty-two pesticides showed consistent, direct associations with prostate cancer incidence across both cohorts. Of these, four pesticides were also associated with prostate cancer mortality. In the replication cohort, each 1-standard-deviation increase in log-transformed pesticide use corresponded to incidence increases per 100,000 individuals (trifluralin, 6.56 [95% confidence interval (CI), 5.04-8.07]; cloransulam-methyl, 6.18 [95% CI, 4.06-8.31]; diflufenzopyr, 3.20 [95% CI, 1.09-5.31]; and thiamethoxam, 2.82 [95% CI, 1.14-4.50]). Limitations included ecological study design, potential unmeasured confounding, and lack of individual-level exposure data. CONCLUSIONS: The results of this study suggest a potential link between certain pesticides and increased prostate cancer incidence and mortality. These findings warrant further investigation of these specific pesticides to confirm their role in prostate cancer risk and to develop potential public health interventions.

The very (radio)active life of Pierre C.C.

PURPOSE: In this short tale, we describe a year of Pierre Chris Curry's ionizing radiation (IR) exposure, assessing and summarizing how much he has been exposed to over a year of his fictive life, cumulating the different types of exposures (either due to natural radiation, occupational and medical exposure), while staying reasonably credible. We have limited ourselves to IR exposure. As a recognized specialist in interventional cardiac surgery, Pierre provides lectures at international conferences requiring overseas flights. When not traveling, Pierre lives in Brittany in an area where there is high natural background radiation, owing to significant concentrations of radon, a radioactive gas produced from the natural radioactive decay of uranium found in rocks, granite in this case. CONCLUSION: Natural exposures correspond to half of Pierre's total yearly exposure. Therefore, where you live, and your life habits have an important impact on your radiation exposure levels. Medical exposures take the second place in the ranking, but these exposures are punctual. Although his professional exposure is the lowest percentage, this represents a chronic exposure which is continuous over the duration of his working life, and alongside the natural exposure, is building on over-time. Although Pierre calculated total yearly dose was 58.4 mSv, significantly higher than the average in countries such as France, UK or even USA, his excess risk of death from cancer was still very low 0.292%.

Trigeminal neuralgia and risk of cancer: A population-based cohort study.

BACKGROUND: Evidence of an association between trigeminal neuralgia (TN) and subsequent cancer risk remains sparse. The present study aimed to examine the association between TN and cancer risk in the Danish population. METHODS: A nationwide population-based cohort study using hospital diagnoses collected routinely and prospectively from Danish population-based registries in 1994-2022. RESULTS: We identified 7846 individuals with a first-time diagnosis of TN. Within one year of diagnosis, we observed 193 cancer cases (standardized incidence rate (SIR) = 2.45, 95% confidence interval (CI) = 2.11-2.82). Absolute risk (AR) for all cancers within one year of TN diagnosis was 2.5% (95% CI = 2.2-2.9). Cancers of the head, neck and nervous system were most strongly associated with TN (AR 0.9% (95% CI = 0.7-1.1); SIR = 13.5 (95% CI = 10.5-17.0)) and the risk was persistently elevated one year after TN diagnosis. We observed 827 cancer diagnoses beyond one year after TN diagnosis, where smoking related cancers were associated with elevated cancer risk (SIR 1.13 = (95% CI = 0.98-1.29)). CONCLUSIONS: TN was associated with an elevated risk of cancers of the head, neck and nervous system including site-specific cancers in the area. Our results suggest the potential importance of smoking related tumors in TN, either as a symptom, cause or shared risk factor.

Smoked and Fermented Bushmeat (Mpunam) Products: Risk Assessment of Polycyclic Aromatic Hydrocarbons (PAHs) Resulting From Processing.

The polycyclic aromatic hydrocarbons (PAHs) congener concentrations and risk upon human exposure to smoked bushmeat products were analyzed. GC/MS MRM and QuEChERS methods were used for the analysis. This work has become necessary due to the need for more information concerning the quantitative determination of these compounds and their health risk assessment. The 16 PAH congeners identified were acenaphthylene (ACA), naphthalene (NAP), acenaphthene (ACE), fluorene (FLU), anthracene (ANT), phenanthrene (PHE), fluoranthene (FLT), pyrene (PYR), benzo[b]fluoranthene (BBF), benzo[k]fluoranthene (BKF), benzo[a]anthracene (BAA), chrysene (CHR), indeno(1,2,3-cd)pyrene (IND), dibenzo(a,h)anthracene (DAA), benzo(g,h,i)pyrene (BGP), and benzo[a]pyrene (BAP). At the 5% and 95% daily intake levels, BAP was at 3.34 and 17.39 µg/kg(bw)/day, ΣPAH4 was at 25.11 and 109.15 µg/kg(bw)/day, and ΣPAH8 was at 55.76 and 236.68 µg/kg(bw)/day, respectively. BAP, ΣPAH4, and ΣPAH8 concentration exceeded the European Union limits, as BAP concentration was as low as 6.09 µg/kg and as high as 34.19. The exposure values were significantly high. Specifically, the margin of exposure for BAP was as low as 2.09 × 10-2; for ΣPAH4, it was 1.36 × 10--2; and for ΣPAH8, it was 1.95 × 10-2 all at the 95% level. These figures are substantially lower than the benchmark of 10,000, indicating a higher ILTCR. Furthermore, the ILTCR ranged from a minimum of 47.77 to a maximum of 248.53 at the 5% and 95% levels, respectively. This study makes smoked bushmeat a public health concern because the higher figures obtained indicate higher carcinogenicity upon consumption.

Assessment of natural radioactivity levels in rice samples and their implications for radiological protection.

This study investigates the levels of natural and artificial radioactivity in rice samples collected from various local markets in Islamabad, Pakistan. The 226Ra, 232Th, and 40K activity concentrations were measured through gamma-ray spectrometry with a NaI(Tl) detector. The average activity concentrations were 1.67 ± 1.19 Bq kg-1 for 226Ra, 3.31 ± 1.83 Bq kg-1 for 232Th, and 88.51 ± 11.65 Bq kg-1 for 40K. Calculated radium equivalent (Raeq) values ranged from 7.35 to 18.08 Bq kg-1, with a mean value of 11.11 Bq kg-1, all below the permissible maximum of 370 Bq kg-1. The absorbed dose rates ranged from 6.85 to 16.39 nGy h-1, with an average of 10.64 nGy h-1, falling below the acceptable limit of 51 nGy h-1. The outdoor and indoor radiation hazard indices (Hex and Hin) had mean values of 0.03, both below the threshold value of one. The external and internal hazard indices (Iγ and Iα) were both 0.088, also below the critical value of one. The excess lifetime cancer risk (ELCR) ranged from 0.28 to 0.11, with a mean value of 0.18, which is less than the critical value of one. Overall, the radioactivity levels in the analyzed rice samples are within the acceptable limits set by the International Commission on Radiological Protection and are below global averages. These results offer important insights into the radiological safety of rice consumption in the study area.

Metabolic obesity phenotypes and thyroid cancer risk: A systematic exploration of the evidence.

Background: Obesity is recognized as a risk factor for various cancers, including thyroid cancer. However, the association between different metabolic obesity phenotypes and thyroid cancer risk remains unclear. This systematic review aimed to comprehensively evaluate the existing literature to elucidate the association between metabolic obesity phenotypes and thyroid cancer risk. Methods: This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were searched for relevant studies until April 2024. Studies examining the link between metabolic obesity phenotypes and thyroid cancer risk were included. Results: Five cohort studies involving 831,510 participants met the inclusion criteria. Metabolically unhealthy obesity was consistently associated with an increased risk of thyroid cancer in both men and women. Central adiposity emerged as a significant predictor of thyroid cancer risk. Mechanistically, chronic inflammation, dysregulated adipokine secretion, hormonal imbalances, and altered signaling pathways may contribute to thyroid carcinogenesis. There is an ongoing debate regarding the risk associated with metabolically healthy obesity, with some suggesting potential protective effects due to favorable metabolic profiles. Conclusion: This systematic review highlights the complex relationship between metabolic obesity phenotypes and thyroid cancer risk. The findings highlighted the importance of considering metabolic status alongside obesity in thyroid cancer risk assessment and intervention strategies.

Increased risk of genitourinary cancer in kidney transplant recipients: a large-scale national cohort study and its clinical implications.

PURPOSE: To investigate the risk of genitourinary (GU) cancer in kidney transplant recipients (KTRs) compared to that in the general population, focusing on potential risk factors and clinical implications. METHODS: Using a national cohort of approximately 360,000 individuals, including 31,542 KTRs, we conducted a retrospective analysis of the data from 2007 to 2018. Propensity score matching was used to compare KTRs with a healthy population, adjusting for age, sex, diabetes, hypertension, and hypercholesterolemia. RESULTS: We identified a significantly increased risk of GU cancers, particularly bladder and kidney cancers, in KTRs. Multivariate analysis revealed a higher risk of GU cancer associated with kidney transplantation [hazard ratio (HR) 2.133, 95% confidence interval (CI) 1.641-2.772] and hypercholesterolemia (HR 1.725, 95% CI 1.227-2.425), with older age and male sex also being significant risk factors. Conversely, no significant increase in prostate cancer risk was observed in KTRs compared to the general population. CONCLUSION: This national cohort-based study indicated an increased risk of GU cancer in KTRs, underscoring the need for targeted cancer surveillance and pre- and post-transplant counseling. These findings provide valuable insights for the development of cancer surveillance programs for KTRs and highlight the necessity for further research in this field.

Mechanisms by Which Pharmacotherapy May Impact Cancer Risk among Individuals with Overweight and Obesity.

Diets geared to reduce cancer risk in overweight and obese individuals focus on (1) caloric restriction (every day, some days, or most hours of each day); (2) changes in macronutrient intake; or (3) a combination of the prior two strategies. Diets generally fail because of nonadherence or due to limited sustained weight loss. This is in contrast to a diet supplemented with a weight loss medication, so long as the participant continues the medication or after bariatric surgery, in which adherence tends to be much higher. Among individuals who regain weight after surgery, weight loss medications are proving beneficial in maintaining weight loss. Both maximum and sustained weight loss are essential for all forms of effective metabolic improvement, including cancer risk reduction. The focus of this report is to assess the state of research on the consequence of pharmacotherapy use on weight loss and proposed weight loss-independent effects on subsequent cancer risk reduction, including the potential role of medication use in conjunction with metabolic (bariatric) surgery (MBS). Finally, we present Notices of Funding Opportunities (NOFOs) by the National Cancer Institute (NCI) to better understand the mechanism(s) that are driving the efficacy of pharmacotherapy in cancer risk reduction.

Long-Term Randomized Controlled Trials of Diet Intervention Reports and Their Impact on Cancer: A Systematic Review.

BACKGROUND: Most randomized controlled trials (RCTs) assessing the impact of diet on cancer have been short term (<1 year), mostly evaluating breast cancer survivors. Given the many-year interval that is generally required for an intervention to have an impact on cancer risk or prognosis, as well as the fact that lifestyle strategies such as diet modification frequently fail due to lack of adherence over the long term, we focused this systematic review only on longer-term (≥1 year) intervention reports. Diet intervention reports focused on reducing cancer risk in overweight and obese individuals target caloric restriction (every day, some days, or most hours of each day). METHODS: This study is a systematic review of RCTs lasting at least 1 year, testing dietary interventions with a primary or secondary endpoint of cancer or a biomarker linked to cancer. RESULTS: Fifty-one reports met our review criteria. Twenty of fifty-one (39%) reports are RCTs where the primary endpoint was cancer or a cancer-related biomarker, while the other reports evaluated reports where cancer or a cancer-related biomarker was a secondary endpoint. Thirteen of twenty (65%) primary reports evaluated isocaloric, and the remaining eight evaluated low-calorie diets. All but one of the primary and two secondary isocaloric diet reports evaluated the benefit of a low-fat diet (LFD), with the other three evaluating a Mediterranean diet (MedD). More LCD vs. isocaloric diet primary reports (71% vs. 38%) demonstrated cancer or cancer-related biomarker benefit; the difference in chance of benefit with secondary reports was 85% for LCD vs. 73% for isocaloric diets. Three of three MedD reports demonstrated benefit. Sixty-nine percent (20/29) of the secondary reports came from two large reports: the WHI diet modification trial (15 secondary reports) and the polyp prevention trial (5 secondary reports). Nineteen of twenty-two (86%) primary reports enrolled only women, and three enrolled both men and women. No study that met our criteria enrolled only men, comprising 1447 men in total vs. 62,054 women. Fifteen of twenty (75%) primary reports focus on healthy women or women with breast cancer. Adherence findings are discussed when provided. CONCLUSIONS: More long-term RCTs evaluating cancer and cancer-related biomarker endpoints are needed, especially for cancers at sites other than the breast.

Understanding the risk of ionizing radiation in breast imaging: Concepts and quantities, clinical importance, and future directions.

BACKGROUND: Conventional mammography remains the primary imaging modality for state-of-the-art breast imaging practice and its benefit (both on diagnostic and screening) was largely reported. In mammography, the typical Mean Glandular Dose (MGD) from X-ray radiation to the breast spans, on average, from 1 to 10 mGy, depending on breast thicknesses, percentage of fibroglandular tissue, and on the examination purpose. METHODS: The aim of this narrative review is to describe the extent of radiation risk in X-ray breast imaging and discuss the main steps and parameters (e.g. MGD, screening frequency and number of examination views) that may have an influence on the radiation risk assessment. RESULTS: Even though the radiation doses used with these examinations are very low, as compared to other medical or natural radiation exposures, there is a non-negligible associated risk of radiation-induced cancer. Accurate radiation risk assessment permits to better balance the overall estimation of the benefit-to-risk ratio in X-ray breast imaging. CONCLUSIONS: It is expected that a better knowledge about radiation-induced cancer risk among population could improve the communications skills between patients and clinicians and could help to increase the awareness in women about radiation risk perception for a transparent and proper informed choice of imaging exam.

The Role of Trace Metals in the Development and Progression of Prostate Cancer.

Over the years, prostate cancer (PCa) research has been of great interest, and trace metals have attracted a lot of attention due to their association with prostate cancer development and progression. PCa has a complex etiology, with genetic, environmental, and lifestyle factors being implicated. Trace metals such as zinc (Zn), mercury (Hg), selenium (Se), lead (Pb), cadmium (Cd), manganese (Mn), arsenic (As), and nickel (Ni) have garnered much attention in recent years, suspected of having direct links to the modulation of cancer risk and progression through their impacts on prostate cancer omics (genomics, epigenetics, proteomics, and transcriptomics). This has led to them being the subject of extensive research in this regard. In this review, we explored the influence of trace metals and offered a comprehensive analysis of the current knowledge on how trace metals affect the biology of prostate cancer at a molecular level by integrating findings from the recent literature to help suggest possible directions for future research.

Effects of personal cancer history and genomic risk information on mothers' psychological adaptation to inherited breast/ovarian cancer syndrome.

This study aimed to understand long-term coping responses of mothers (N = 287) receiving genetic counseling and testing (GCT) for hereditary breast/ovarian cancer (HBOC) syndrome. Psychological characteristics, including cancer-specific distress (Impact of Events Scale-Revised, α = .85) and coping (Brief COPE, α = .93) were assessed via structured personal communication, along with epidemiologic items assessing personal and family history of cancer. Genetic risk was determined by BRCA1/2 carriage. A principal component analysis was conducted on the coping measure to reduce its summary score to active coping (α = .91) with nine approach-oriented strategies responsive to stress. A multivariable regression model examined the main and interacting effects of clinical and psychological characteristics on maternal coping. Personal cancer history (F = 4.99, df = 1, p = .026), BRCA test result (F = 22.20, df = 1, p < .001), and cancer-specific distress (F = 17.80, df = 1, p < .001) were associated with greater engagement in active coping strategies. When controlling for cancer-specific distress, the interaction between personal cancer history and genetic test results was significant, such that women previously unaffected by cancer who received positive BRCA results reported the greatest levels of active coping (F = 7.92, p < .001). These findings indicate that previous cancer history, genetic risk, and psychological distress independently and jointly impact how women adapt to the threat of cancer over time.

Human and environmental risk assessment and plausible sources of toxic heavy metals at beach placers in southeast Sri Lanka.

Beach placers are typically rich in heavy minerals, which are crucial for a wide range of industrial applications. This study investigates the human and environmental risks posed by toxic heavy metals (As, Pb, Zn, Cu, Cr, Fe, V and Mn) in beach placers of southeastern Sri Lanka using 42 X-ray fluorescence data. Risk indicators (EF, Igeo, CF and PLI) indicate the polluted nature of the placers. Correlation analysis (correlation matrix and HCA) identified pollution sources as heavy mineral-rich rocks, agricultural fertilizers, pesticides and municipal wastes. The environmental impact caused by toxic metals is less in placers. The highest non-carcinogenic risks (HI) resulted by Cr (1.69E+00), V (4.29E+00) and Fe (2.06E+00) to children. The total cancer risk of As and Cr in placers is unacceptable (children: 2.60E-04, 2.48E-03, and adults: 3.14E-05, 2.87E-04, respectively). Different strategies are introduced to mitigate the identified risks in source areas and the coastal environment.

Transfer factors of naturally occurring radionuclides from soil-to-rice cultivated in Bangladesh and associated health implications.

This study investigates the uptake of naturally occurring radionuclides (226Ra, 232Th, and 40K) from soil by rice plants in extensively cultivated regions in Bangladesh. It also evaluates the potential radiation risks associated with rice consumption by the Bangladeshi populace. High purity germanium (HPGe) gamma-ray spectrometry was employed to measure the concentrations of radionuclides in both soil and rice samples. For 40K, our results agree with the International Atomic Energy Agency's (IAEA) published value; however, the transfer factors (TF) for the other two radionuclides differ considerably. Despite the fact that the IAEA based its publication of TFs for 226Ra and 232Th on clay soil, the majority of the soil profile in the present study was silty clay with a little alkalinity. Moreover, the data obtained may have been impacted by the growing seasons, cultivation methods, and soil fertility. Additionally, the annual effective dose due to the ingestion of radioactivity resulting from rice consumption was evaluated and the results agree with UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation), 2000. With a few exceptions, the excess lifetime cancer risk (ELCR) values for 226Ra, 232Th, and 40K were below the globally average permissible level (1 × 10-3). In light of this, the current study indicates that consuming rice does not pose an immediate health risk to the general public. By studying TFs among various rice varieties and geographical areas, scientists can develop models to forecast the possible radiation exposure from rice consumption and pinpoint activities or areas that require additional attention.

Ovotesticular Disorders of sexual development (DSD): A rare case of peritoneal carcinomatosis in an elderly DSD male patient.

Disorders of sexual development (DSDs) represent a spectrum of conditions characterized by atypical gonadal and/or genital development. The incidence is 1 in 5,000 live births. Patients with DSD may be at increased risk for developing gonadal and reproductive tract tumors. This report summarizes the current knowledge on the risks of gonadal tumors in patients with DSD. Specifically, we focus on ovotesticular DSD (OT-DSD), which accounts for 5% of DSD cases and is defined by the presence of both ovarian and testicular tissues in the same individual. We present a rare case of a phenotypically male XY patient with OT-DSD who was diagnosed with aggressive peritoneal cancer at the age of 71.

Gut Microbiome and Hepatic Transcriptomic Determinants of HCC Development in Mice with Metabolic Dysfunction-Associated Steatohepatitis.

Purpose: Hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) is often diagnosed at a late stage, and its incidence is increasing. Predictive biomarkers are therefore needed to identify individuals at high risk of HCC. We aimed to characterize the gut microbiome and hepatic transcriptome associated with HCC development in female mice with hepatocyte-deletion of Pten (HepPten -). These mice present with large variations in HCC development, making them a powerful model for biomarker discovery. Methods & Results: Sequencing of stool 16S and hepatic RNA was performed on a first set of mice. Among all liver histology parameters measured, the strongest association with microbiome composition changes was with the number of tumors detected at necropsy, followed by inflammation. The gut microbiome of mice with more than 2 tumors was enriched with Lachnospiraceae UCG and depleted of Palleniella intestinalis and Odoribacter. In contrast, hepatic transcriptomic changes were most strongly associated with tumor burden, followed by liver fibrosis. The 840 differentially expressed genes correlating with tumor burden were enriched in leukocyte extravasation and interleukin 10 receptor A (IL10RA) pathways. In addition, the abundance of Spp1-high epithelial cells is correlated with tumor burden. Association between tumor number and depletion of Palleniella intestinalis, and between tumor burden and circulating levels of C-X-C motif chemokine ligand 13 (CXCL13) and stem cell factor (SCF), was further validated in an independent set of mice. Conclusion: We identified microbiome components contributing to liver carcinogenesis by inducing inflammation, and changes in hepatic gene expression and hepatic cells distribution that contribute to tumor growth. Such information can be highly valuable for the development of new prevention strategies as well as of new biomarkers for risk modeling in HCC.