Established Cancer Risk Factors Research Articles

Fat Matters: Exploring Cancer Risk through the Lens of Computed Tomography and Visceral Adiposity.

Obesity is an established risk factor for cancer. However, conventional measures like body mass index lack precision in assessing specific tissue quantities, particularly of the two primary abdominal fat compartments, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Computed tomography (CT) stands as the gold standard for precisely quantifying diverse tissue types. VAT, distinguished by heightened hormonal and metabolic activity, plays a pivotal role in obesity-related tumor development. Excessive VAT is linked to aberrant secretion of adipokines, proinflammatory cytokines, and growth factors, fostering the carcinogenesis of obesity-related tumors. Accurate quantification of abdominal fat compartments is crucial for understanding VAT as an oncological risk factor. The purpose of the present research is to elucidate the role of CT, performed for staging purposes, in assessing VAT (quantity and distribution) as a critical factor in the oncogenesis of obesity-related tumors. In the field of precision medicine, this work takes on considerable importance, as quantifying VAT in oncological patients becomes fundamental in understanding the influence of VAT on cancer development-the potential "phenotypic expression" of excessive VAT accumulation. Previous studies analyzed in this research showed that VAT is a risk factor for clear cell renal cell carcinoma, non-clear cell renal cell carcinoma, prostate cancer, and hepatocarcinoma recurrence. Further studies will need to quantify VAT in other oncological diseases with specific mutations or gene expressions, in order to investigate the relationship of VAT with tumor genomics.

Population attributable proportion and number of cancer cases attributed to potentially modifiable risk factors in Iran in 2020.

In the current study, we aimed to calculate the fraction of cancer attributable to modifiable risk factors in Iran in 2020. Population attributable fractions (PAFs) were calculated for established cancer risk factors using three data sources: the national cancer incidence reports, relative risks extracted from global and national meta-analyses, and exposure prevalence from national/subnational population-based surveys. In addition to overall cancers, the PAFs were estimated separately for each cancer site among men and women. Overall, 32.6% of cancers in 2020 in Iran were attributable to known risk factors. The PAF in men (40.2%) was twice as high as in women (21.1%). Cigarette smoking (15.4%), being overweight (5.0%), opium use (3.9%) and H. pylori infection (3.8%) were the leading causes of cancers. For men, the highest PAFs belonged to cigarette smoking (26.3%), opium use (6.8%) and being overweight (3.1%), while for women, the highest PAFs belonged to being overweight (7.2%), H. pylori infection (2.7%) and cigarette smoking (2.7%). Among Iranian men and women, the PAFs of waterpipe smoking were 2% and 0.9%, respectively. A third of incident cancers in Iran are due to modifiable exposures, mainly cigarette smoking, being overweight, and H. pylori infection. Opium consumption and waterpipe smoking collectively accounted for 8.8% of cancer occurrence in men and 1.3% in women in Iran. These emerging risk factors should be taken into consideration in future PAF studies.

Non-exercise estimated cardiorespiratory fitness and cancer incidence: The NIH-AARP diet and health study

BackgroundNon-exercise estimated cardiorespiratory fitness (NEE-CRF) has been shown to be associated with mortality, although its association with cancer incidence is unknown. The study aimed to assess the prospective association between NEE-CRF and cancer incidence in a large cohort of men and women. MethodsThe National Institutes of Health-American Association of Retired Persons diet and health study is a prospective cohort that included 402,548 participants aged 50–71 years who were free from cancer at baseline (1995–1996) (men (n = 238,835) and women (n = 163,713)) and were followed until December 31, 2015. The exposure variable was NEE-CRF expressed in metabolic equivalents. NEE-CRF was estimated using a validated equation of self-reported predictors on demographics and lifestyle behaviors derived from baseline questionnaires. Primary outcomes were total cancer incidence and incidence of prostate, breast, lung, and colorectal cancers. Cox proportional hazards models were analyzed for the association between NEE-CRF and cancer incidence outcomes adjusted for established cancer risk factors. ResultsDuring 13.7 ± 3.2 years of follow-up (mean ± SD), 64,344 men and 31,315 women developed a new cancer. For every 1-metabolic equivalent higher NEE-CRF, the hazard ratios and 95% confidence intervals (95%CIs) were 0.96 (95%CI: 0.94–0.97) and 0.88 (95%CI: 0.84–0.92) of total and colorectal cancer incidence among men, and 0.95 (95%CI: 0.93–0.97) and 0.94 (95%CI: 0.91–0.97) of total and breast cancer incidence among women, respectively (all p < 0.001). NEE-CRF was not associated with incidence of prostate and lung cancers in men or colorectal and lung cancers in women. ConclusionThese results suggest that higher CRF levels, as assessed by the applied non-exercise estimated method, may provide preventive benefits against the development of cancer, while low CRF could potentially serve as a modifiable cancer risk factor. Integrating NEE-CRF into screening paradigms and referring low-fit individuals to improve CRF could complement the public health prevention strategy against cancer.

DIETARY-BASED MOLECULAR TARGETS AND THERAPEUTIC OPPORTUNITIES IN CANCER

Diet influence human health in different ways. But it is well known that diet can adversely affect various human pathologies, like obesity, diabetes, hypertension, and cancer. The relationship between diet, obesity and cancer has been studied for different types of cancer such as breast, colorectal and gastric cancers. High fat diet induced obesity is an established risk factor for cancer in many tissues. In the mammalian intestine, tumorigenesis is facilitated by a pro-obesity high-fat diet (HFD) by enhancing PPAR (peroxisome proliferator-activated receptor) nuclear receptor activation. PPARs induced fatty acid oxidation increased stem cell number and tumorigenesis. The rate controlling enzyme of fatty acid oxidation, CPT1A, dampens the pro-tumorigenic phenotype by blunting HFD effect in ISCs. High-fat ketogenic diet also elevates ISC function and regeneration capacity through βOHB-mediated Notch signaling, but a glucose-supplemented diet has the opposite effects. High glucose diet also presents an indirect link between sugar and cancer. The relationship dietary supplements used in addition to the diet and cancer is frequently studied. In literature, there is strong evidence on the anticancer effects of anthocyanins, curcumin, vitamin D, and their mechanisms.

CDK5RAP3, a New BRCA2 Partner That Regulates DNA Repair, Is Associated with Breast Cancer Survival.

Simple SummaryBRCA2 is an essential gene for DNA repair by homologous recombination and is often mutated in families at risk of breast and ovarian cancer. In this study we identified CDK5RAP3 tumor suppressor as a new BRCA2-interacting protein. CDK5RAP3 negatively regulates DNA repair of double-strand breaks, providing a new mechanism of DNA damage resistance. Consistently, gene expression data analysis showed CDK5RAP3 overexpression in breast cancer is associated with poorer survival. Finally, we identified common genetic variations in the CDK5RAP3 locus as potentially associated with breast and ovarian cancer risk in a large cohort of BRCA1 and BRCA2 mutation carriers.BRCA2 is essential for homologous recombination DNA repair. BRCA2 mutations lead to genome instability and increased risk of breast and ovarian cancer. Similarly, mutations in BRCA2-interacting proteins are also known to modulate sensitivity to DNA damage agents and are established cancer risk factors. Here we identify the tumor suppressor CDK5RAP3 as a novel BRCA2 helical domain-interacting protein. CDK5RAP3 depletion induced DNA damage resistance, homologous recombination and single-strand annealing upregulation, and reduced spontaneous and DNA damage-induced genomic instability, suggesting that CDK5RAP3 negatively regulates double-strand break repair in the S-phase. Consistent with this cellular phenotype, analysis of transcriptomic data revealed an association between low CDK5RAP3 tumor expression and poor survival of breast cancer patients. Finally, we identified common genetic variations in the CDK5RAP3 locus as potentially associated with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Our results uncover CDK5RAP3 as a critical player in DNA repair and breast cancer outcomes.

Evaluation of Early-Life Factors and Early-Onset Colorectal Cancer Among Men and Women in the UK Biobank

Evaluation of Early-Life Factors and Early-Onset Colorectal Cancer Among Men and Women in the UK Biobank

SYNCHRONOUS ORAL SQUAMOUS CELL CARCINOMA (SCC) AND LUNG ADENO-CARCINOMA—THE VALUE OF SCREENING CHEST COMPUTED TOMOGRAPHY (CT): A CASE SERIES

Background Lung cancer is present in 1.1% of patients with oral (head and neck) SCC. Guidelines recommend that all patients with head and neck SCC receive chest computed tomography (CT) as part of their diagnostic and surgical evaluation, given that smoking is an established risk factor for cancer of both sites. The diagnosis of a synchronous lung cancer will alter the treatment of the patient. Case 1 An 85-year-old man with a 60 pack-year smoking history presented with a T1N0M0 floor of mouth SCC. His ECOG performance status was 1. CT demonstrated a 23-mm spiculated mass in the right upper lung lobe. Positron emission tomography demonstrated avidity in the lung mass (SUV 7.8), as well as multiple mildly avid associated lymph nodes. Lung biopsy demonstrated an infiltrative adenocarcinoma. Endobronchial ultrasound-guided fine-needle aspiration biopsies of the lymph nodes were unremarkable. The patient underwent stereotactic radiation therapy for lung cancer and is awaiting definitive surgery for his oral cancer. Case 2 A 53-year-old man with a 50 pack-year smoking history presented with a T3N2 floor of mouth SCC. CT and positron emission tomography demonstrated a 44-mm apical mass of the left lung, invading the mediastinum. Treatment of the oral SCC was deferred until confirmatory biopsy with a view to management of the suspected lung cancer. Conclusions These cases highlight the value of chest CT chest as part of the comprehensive evaluation of patients presenting with oral (head and neck) cancer. Lung cancer is present in 1.1% of patients with oral (head and neck) SCC. Guidelines recommend that all patients with head and neck SCC receive chest computed tomography (CT) as part of their diagnostic and surgical evaluation, given that smoking is an established risk factor for cancer of both sites. The diagnosis of a synchronous lung cancer will alter the treatment of the patient. An 85-year-old man with a 60 pack-year smoking history presented with a T1N0M0 floor of mouth SCC. His ECOG performance status was 1. CT demonstrated a 23-mm spiculated mass in the right upper lung lobe. Positron emission tomography demonstrated avidity in the lung mass (SUV 7.8), as well as multiple mildly avid associated lymph nodes. Lung biopsy demonstrated an infiltrative adenocarcinoma. Endobronchial ultrasound-guided fine-needle aspiration biopsies of the lymph nodes were unremarkable. The patient underwent stereotactic radiation therapy for lung cancer and is awaiting definitive surgery for his oral cancer. A 53-year-old man with a 50 pack-year smoking history presented with a T3N2 floor of mouth SCC. CT and positron emission tomography demonstrated a 44-mm apical mass of the left lung, invading the mediastinum. Treatment of the oral SCC was deferred until confirmatory biopsy with a view to management of the suspected lung cancer. These cases highlight the value of chest CT chest as part of the comprehensive evaluation of patients presenting with oral (head and neck) cancer.

High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity.

SUMMARYObesity is an established risk factor for cancer in many tissues. In the mammalian intestine, a pro-obesity high-fat diet (HFD) promotes regeneration and tumorigenesis by enhancing intestinal stem cell (ISC) numbers, proliferation, and function. Although PPAR (peroxisome proliferator-activated receptor) nuclear receptor activity has been proposed to facilitate these effects, their exact role is unclear. Here we find that, in loss-of-function in vivo models, PPARα and PPARδ contribute to the HFD response in ISCs. Mechanistically, both PPARs do so by robustly inducing a downstream fatty acid oxidation (FAO) metabolic program. Pharmacologic and genetic disruption of CPT1A (the rate-controlling enzyme of mitochondrial FAO) blunts the HFD phenotype in ISCs. Furthermore, inhibition of CPT1A dampens the pro-tumorigenic consequences of a HFD on early tumor incidence and progression. These findings demonstrate that inhibition of a HFD-activated FAO program creates a therapeutic opportunity to counter the effects of a HFD on ISCs and intestinal tumorigenesis.

MO481KIDNEY FUNCTION MEASURES AND THE RISK OF CANCER INCIDENCE, CANCER DEATH AND ALL-CAUSE MORTALITY*

Abstract Background and Aims Cancer is more common in end-stage kidney disease and in patients on dialysis. We hypothesise that chronic kidney disease (CKD) across the spectrum of disease is associated with increased risk of cancer incidence and cancer death and that this risk is independent of known risk factors for cancer. Furthermore, we assess if risk of cancer incidence (overall and cancer subtypes), cancer death and all-cause mortality is more strongly associated with kidney function-estimating equations incorporating cystatin C. Method Participants from UK Biobank with baseline measurements of serum creatinine and cystatin C were included, excluding patients with pre-existing cancer. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI formulae for creatinine (eGFRcr), cystatin C (eGFRcys) and a combination of creatinine and cystatin C (eGFRcr-cys). Associations of each eGFR with incidence and mortality from overall and specific cancer sites as well as all-cause mortality were tested using Cox proportional hazards models, adjusted for established risk factors for cancer (age, sex, smoking status, alcohol intake, body mass index, ethnicity and deprivation index). Results .In 443,441 eligible participants in UK Biobank over median follow-up of 11.3 (IQR 10.6-12.0) years, there were 41,991 incident cancers, 11,854 cancer deaths and 23,708 total deaths. After adjustment for established cancer risk factors and compared to those without significant CKD (eGFR &amp;gt;60 ml/min/1.73m2), CKD G3-5 (eGFR &amp;lt;60 ml/min/1.73m2) was associated with an increased risk of cancer incidence (eGFRcr-cys HR 1.16 (95% CI 1.10 – 1.22); p&amp;lt;0.001), cancer death (eGFRcr-cys HR 1.36 (95% CI 1.25 – 1.48); p&amp;lt;0.001) and all-cause mortality (eGFRcr-cys HR 2.29 (95% CI 2.18-2.41); p&amp;lt;0.001). CKD G3-5 was more strongly associated with risk of cancer incidence, cancer death and all-cause mortality in younger men and women (age &amp;lt;65 years). In particular, younger men and women with CKD G3-5 were more than twice as likely to die from cancer than younger men and women without CKD (eGFRcr-cys HR 2.39 (95% CI 1.99-2.87); p&amp;lt;0.001 and HR 2.12 (95% CI 1.72-2.62); p&amp;lt;0.001 respectively). CKD G3-5 was associated with increased risk of cancer of the abdominal solid organs (eGFRcr-cys HR 1.31 (95% CI 1.07-1.60); p=0.009), respiratory (eGFRcr-cys HR 1.36 (95% CI 1.18-1.56); p&amp;lt;0.001) and renal tracts (eGFRcr-cys HR 1.38 (95% CI 1.18-1.61); p&amp;lt;0.001) and haematological cancers (eGFRcr-cys HR 1.77 (95% CI 1.54-2.03); p&amp;lt;0.001), but was not associated with increased risk of female (breast and reproductive system) or male (prostate, penile and testicular) cancers, cancers of the digestive tract or melanoma (Figure below). For all outcomes, the strongest associations were found using measures that incorporated cystatin C and were similar for eGFRcys and eGFRcr-cys. Conclusion These data support routine implementation of cystatin C testing to identify individuals at increased risk of cancer. Younger men and women in particular are increased risk of cancer incidence and cancer death in the context of CKD G3-5. Further exploration is warranted to identify the reasons for worse cancer outcome, particularly in younger patients with CKD.

Lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.

e16271 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) &gt; 27 (obese [n = 21]) and BMI &lt; 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. We have also shown that there are fewer total cells per area in the tumor region, suggesting a disorganization that may allow more adipose tissue to form in these areas of high BMI patients. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.

Significant lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.

438 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) &gt; 27 (obese [n = 21]) and BMI &lt; 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.

Long-term anti-inflammatory diet in relation to improved breast cancer prognosis: a prospective cohort study

Inflammation-modulating nutrients and inflammatory markers are established cancer risk factors, however, evidence regarding the association between post-diagnosis diet-associated inflammation and breast cancer survival is relatively sparse. We aimed to examine the association between post-diagnosis dietary inflammatory index (DII®) and risks of all-cause and breast cancer-specific mortality. A total of 1064 female breast cancer survivors in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) Trial prospective cohort, were included in this analysis if they had completed the diet history questionnaire (DHQ). Energy-adjusted DII (E-DIITM) scores were calculated based on food and supplement intake. Cox regression and competing risk models were used to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (95% CIs) by E-DII tertile (T) for all-cause and breast cancer-specific mortality. With median follow-up of 14.6 years, there were 296 (27.8%) deaths from all causes and 100 (9.4%) breast cancer-specific death. The E-DII was associated with all-cause mortality (HR T3 vs T1, 1.34; 95% CI, 1.01–1.81; Ptrend, 0.049, Table 2) and breast cancer mortality (HR T3 vs T1, 1.47; 95% CI, 0.89–2.43; Ptrend, 0.13; multivariable-adjusted HR for 1-unit increment: 1.10; 95% CI: 1.00–1.22). Non-linear positive dose–response associations with mortality from all causes were identified for E-DII scores (Pnon-linearity < 0.05). The post-diagnosis E-DII was statistically significantly associated with mortality risk among breast cancer survivors. Long-term anti-inflammatory diet might be a means of improving survival of breast cancer survivors.

Association between rs1229984 in ADH1B and cancer prevalence in a Japanese population.

Alcohol consumption is an established risk factor for cancer, but little is known regarding the effect of genetic polymorphisms in alcohol metabolism genes on alcohol-related cancer risk in the Japanese population. Associations between the ADH1B gene (alcohol dehydrogenase 1B), single nucleotide polymorphism (SNP) rs1229984 and cancer have been extensively studied yet evidence is inconsistent. This population-based case-control study primarily aimed to clarify any association between SNP rs1229984 in both overall and specific cancer risk in a Japanese population. The functional non-synonymous SNP rs1229984 (Arg48His) was genotyped using DNA samples from 1,359 consecutive autopsy cases registered in The Japanese Single Nucleotide Polymorphisms for Geriatric Research database. Medical and pathological record data from this database were used to categorise cases and controls. Results included 1,359 participants, 816 cases and 543 controls. Multinomial logistic regression analyses showed no significant association between rs1229984 presence and overall cancer risk in both dominant and recessive genetic inheritance models [Arg/Arg+Arg/His vs. His/His: Adjusted odds ratio (OR)=0.66 (95% CI=0.39-1.13; P=0.129), Arg/Arg vs. Arg/His+His/His: OR=0.95 (95% CI=0.75-1.20; P=0.657)]. However, results showed those homozygous for rs1229984 (genotype His/His) were at significantly decreased odds of lung cancer than other genotypes [recessive model: OR=0.64 (95% CI=0.44-0.93; P=0.020]. In conclusion, there was no significant association between rs1229984 and odds of overall or specific cancers except in lung cancer where His/His genotype decreased odds. To the best of our knowledge, the association between His/His and decreased odds of lung cancer is a novel finding. These findings require further validation in larger studies.

Significant neutrophil accumulation, IL-18 deposition, and active inflammasome in tumor regions of human pancreatic ductal adenocarcinoma.

e15754 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients with a body-mass index (BMI) &gt; 27 (obesity, n = 5) and BMI &lt; 22 (normal, n = 5) were incubated with anti-human IL-18 and CD66b antibodies and detected using Alexa Fluor 488-conjugated donkey anti–mouse and Alexa Fluor 594-conjugated goat anti-rabbit secondary antibodies. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of CD66b+ neutrophils and IL-18 in all tissue sections. There is a significantly greater density of CD66b+ neutrophils and IL-18 in the tumor environment when compared to adjacent normal areas and IL-18+ signals appear to be deposited alongside the luminal area in a unique lasso-like pattern. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. There does not appear to be an association between tumor stage and TAN or IL-18 accumulation in the tumor area or the adjacent normal tissue in the tissues. Conclusions: Our data uniquely shows that CD66b+ neutrophils accumulate inside PDAC and this is associated with intra-tumoral active inflammasomes. The novel periductal deposition of IL-18 in the tumor areas may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.

Awareness of cancer risk factors and protective factors among Australian adults.

Up to one-third of incident cancers in Australia are attributable to modifiable factors. Understanding the general public's awareness of cancer risk and protective factors is important for identifying knowledge gaps and informing the development of effective and targeted health promotion strategies. In a telephonic survey of 355 Western Australian adults aged 18-54years (48% male), with a sample skewed towards low-socio-economic status areas, respondents rated the effect on cancer risk of 11 established cancer risk factors and seven established cancer protective factors. Most respondents correctly recognised the increased cancer risk from sun tanning (94%), asbestos (92%), pesticide use (92%) and being overweight or obese (86%), and the protective effect of being physically active (82%). Half (52%) of respondents incorrectly believed that red wine decreased or had no effect on cancer risk. One in five respondents (19%) incorrectly believed that sunscreen use increased cancer risk. Only 18% of respondents were aware that human papillomavirus (HPV) vaccination confers a protective effect, while 17% believed it increases risk. Although the majority of respondents were aware of certain established cancer risk and protective factors, a sizeable proportion held misconceptions about the cancer risk associated with red wine consumption, sunscreen use and HPV vaccination. SO WHAT?: Health promotion programs designed to educate the public about modifiable cancer risk factors may need to increase public awareness of the safety of preventive factors such as HPV vaccination and sunscreen, and the increased cancer risk from consumption of all alcoholic beverage types, including red wine.

Cardiorespiratory fitness and cancer in women: A prospective pilot study

PurposeTo assess the association between cardiorespiratory fitness (CRF) and the incidence and mortality from cancer in women, and to evaluate the potential public health implications for cancer prevention. MethodsMaximal exercise testing was performed in a pilot cohort of 184 women (59.3 ± 15.2 years) who were followed for 12.0 ± 6.9 years. Cox hazard models adjusted for established cancer risk factors and accounting for competing events were analyzed for all-type cancer incidence and mortality from cancer. Population-attributable risks and exposure impact number were determined for low CRF (<5 metabolic equivalents (METs)) as a risk factor. ResultsDuring the follow-up, 11.4% of the participants were diagnosed with cancer and 3.2% died from cancer. CRF was inversely and independently associated with cancer outcomes. For every 1-metabolic equivalent increase in CRF, there was a 20% decrease in the risk of cancer incidence (hazard ratio (HR) = 0.80, 95% confidence interval (CI): 0.69–0.92; p = 0.001) and a 26% reduction in risk of cancer mortality (HR = 0.74, 95%CI: 0.61–0.90; p = 0.002). The population-attributable risks of low CRF were 11.6% and 14% for incidence and mortality of cancer, respectively, and the respective exposure impact numbers were 8 and 20. ConclusionGreater CRF was independently associated with a lower risk of incidence and mortality from cancer in women. Screening for low CRF as a cancer risk factor and referring unfit individuals to a supervised exercise program could be a public health strategy for cancer prevention in middle-age women.

Cardiorespiratory fitness, incidence and mortality of lung cancer in men: A prospective cohort study

ObjectivesTo evaluate the association between cardiorespiratory fitness (CRF), lung cancer incidence and cancer mortality in men. DesignProspective cohort study. MethodsMaximal exercise testing was performed in 4920 men (59.2±11.4years) free from malignancy at baseline. Multivariate Cox hazard models adjusted for established cancer risk factors including smoking were analyzed for lung cancer incidence and cancer mortality among those who were diagnosed with lung cancer. Population attributable risks (PAR) of low CRF (<5 METs) were determined. ResultsDuring 12.7±7.5years follow-up, 105 (2.1%) participants were diagnosed with lung cancer and 83 (79%) of those died from cancer after 3.6±4.6 years from diagnosis. CRF was inversely and independently associated with cancer outcomes. A 1-MET increase and categories of moderate and high CRF were associated with 10%, 47% and 65% reduction in lung cancer incidence (p=0.002), and 13%, 58% and 76% reduction in cancer mortality (p=0.002), respectively. Also, individuals who were diagnosed with lung cancer and were at moderate or high CRF categories at baseline exhibited longer survival time (p<0.001). The PARs% for lung cancer incidence and cancer mortality were 8.7% and 18.5%, respectively. ConclusionsHigher CRF is associated with lower lung cancer incidence in men. Among individuals who were diagnosed with lung cancer, higher CRF was associated with reduced cancer mortality and longer survival time. These results support the protective benefits of higher CRF in the prevention of lung cancer outcomes. Eliminating low CRF as a risk factor would potentially prevent considerable lung cancer morbidity and mortality.

Differentiation Patterns of Uterine Carcinomas and Precursor Lesions Induced by Neonatal Estrogen Exposure in Mice.

Developmental exposure to estrogenic chemicals is an established risk factor for cancer of the female reproductive tract. This increase in risk has been associated with disruption of normal patterns of cellular differentiation during critical stages of morphogenesis. The goal of this study was to document uterine epithelial phenotypes over time following neonatal treatment with the synthetic estrogen diethylstilbestrol (DES) or the soy phytoestrogen genistein (GEN) in female CD-1 mice. Both DES and GEN induced three distinct populations of abnormal endometrial epithelial cells: luminal (SIX1+/P63-/CK14-/CK18+), basal (SIX1+/P63+/CK14+/CK18-), and mixed/bipotential (SIX1+/P63-/CK14+/CK18+), which were all established by early adulthood. In older animals, DES and GEN resulted in uterine carcinomas with mixed glandular, basal, and squamous cell elements. All carcinomas were composed largely of the three abnormal cell types. These findings identify novel epithelial differentiation patterns in the uterus and support the idea that disruption of cellular programming in early development can influence cancer risk later in life.

Obesity and Prognostic Variables in Colombian Breast Cancer Patients: A Cross-Sectional Study.

Introduction Obesity is an established risk factor for cancer and cancer-related deaths, including that of the breast. While the prevalence of female obesity has accelerated over the past decade in many developing countries, such as Colombia, the prevalence of overweight and obesity specifically in breast cancer populations has not been fully described. Methods A cross-sectional study including 849 women diagnosed with breast cancer between 2009 and 2014. Based on body mass index, prevalence of overweight (BMI ≥ 25 < 30) and obesity (BMI ≥ 30) and associations of BMI with clinical and tumor histopathological features were analyzed. Results Colombian breast cancer patients had a prevalence of overweight of 34.28% and obesity of 28.15%. Mean BMI was comparable between premenopausal and postmenopausal women (27.2 versus 27.7, resp.). Among premenopausal women, higher BMI was significantly positively associated with hormone receptor negative tumors, as well as with greater lymphovascular invasion. Conclusions Colombian breast cancer patients exhibit a significant prevalence of overweight and obesity. Associations of high BMI and poor prognosis variables in the premenopausal population suggest risk of aggressive disease in this population. Future studies to further validate our observations are warranted in order to implement multidisciplinary clinical guidelines.

Gamma-glutamyltransferase and risk of prostate cancer: Findings from the KIHD prospective cohort study.

Increased circulating serum gamma-glutamyltransferase (GGT) has been linked with an increased risk of chronic disease outcomes, including overall and several site-specific cancers. However, the relationship of GGT with prostate cancer risk is uncertain. We aimed to assess the prospective association of GGT with risk of prostate cancer. Serum GGT activity was assessed at baseline in the Finnish Kuopio Ischemic Heart Disease prospective cohort of 2,390 men aged 42-61 years without a history of cancer at baseline. We corrected for within-person variability in GGT values using data from repeat measurements taken several years apart. During a median follow-up of 24.6 years, 230 cases of prostate cancer occurred. The age-adjusted regression dilution ratio for loge GGT was 0.69 [95% confidence interval (CI): 0.63-0.74]. Serum GGT was nonlinearly associated with risk of prostate cancer. In age-adjusted Cox regression analysis, the hazard ratio (95% CIs) for prostate cancer in a comparison of the top quartile versus bottom quartiles 1-3 of GGT values was 1.43 (1.07 to 1.93; p = 0.017), which persisted on adjustment for several established cancer risk factors 1.46 (1.06 to 2.02; p = 0.020). The association remained unchanged on further adjustment for total energy intake, socioeconomic status, physical activity and C-reactive protein. The association did not importantly vary across several clinical subgroups. GGT is positively and independently associated with future risk of prostate cancer in a middle-aged Finnish male population over long-term follow-up. Further research is needed to understand the mechanistic pathways involved and if GGT may have potential relevance in prostate cancer prevention.