Risk Of Several Cancer Types Research Articles

Cancer risk based on alcohol consumption levels: a comprehensive systematic review and meta-analysis.

Alcohol consumption is a well-established risk factor for cancer. Despite extensive research into the relationship between alcohol consumption and cancer risk, the effect of light alcohol consumption on cancer risk remains a topic of debate. To contribute to this discourse, we conducted a comprehensive systematic review and meta-analysis. Our systematic review aimed to investigate the associations between different levels of alcohol consumption and the risk of several cancer types. We focused on analyzing prospective associations using data from 139 cohort studies. Among them, 106 studies were included in the meta-analysis after a quantitative synthesis. Our analysis did not find a significant association between light alcohol consumption and all-cause cancer risk (relative risk, 1.02; 95% confidence interval, 0.99 to 1.04), but we observed a dose-response relationship. Light alcohol consumption was significantly associated with higher risks of esophageal, colorectal, and breast cancers. Light to moderate drinking was associated with elevated risks of esophageal, colorectal, laryngeal, and breast cancers. Heavy drinking was also found to contribute to the risk of stomach, liver, pancreas, and prostate cancers, thereby increasing the risk of almost all types of cancer. Additionally, females generally had lower cancer risks compared to males. Our findings highlight that cancer risks extend beyond heavy alcohol consumption to include light alcohol consumption as well. These findings suggest that there is no safe level of alcohol consumption associated with cancer risk. Our results underscore the importance of public health interventions addressing alcohol consumption to mitigate cancer risks.

Use of Dietary Fibers in Reducing the Risk of Several Cancer Types: An Umbrella Review.

(1) Background: Numerous meta-analyses have shown that a high intake of dietary fiber plays a protective role in preventing the development of various types of cancer. However, previous studies have been limited by focusing on a single type of dietary fiber and variations in outcome measures, which may not be effectively applied to provide dietary guidance for the general population. (2) Object: We summarized the meta-analysis of dietary fiber and cancer, and provided references for residents to prevent cancer. (3) Methods: Systematic search of relevant meta-analyses on the association between dietary fiber and cancer occurrence in PubMed, Web of Science and other databases was conducted from the time of database construction to February 2023. The method logical and evidence quality assessments were performed by applying the criteria in the "A Measurement Tool to Assess Systematic Reviews-2" (AMSTAR2) scale and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Expert Report, respectively. (4) Results: Our analysis included 11 meta-analyses, and the AMSTAR 2 assessment revealed that the overall methodological quality was suboptimal, with two key items lacking sufficient information. Nonetheless, our findings indicate that a high intake of dietary fiber is associated with a reduced risk of several types of cancer, including esophageal, gastric, colon, rectal, colorectal adenoma, breast, endometrial, ovarian, renal cell, prostate, and pancreatic cancers. The majority of these associations were supported by a "probable" level of evidence. (5) Conclusions: Dietary fiber intake has different protective effects on different cancers.

Abstract 903: Metformin antitumoral activity is exclusively mediated by the membrane functional expression of the Chloride Intracellular Channel 1 in glioblastoma stem cells

Abstract Glioblastoma (GB) is the deadliest brain tumor, representing a major clinical challenge in the field. Despite standard of care together with cutting-edge strategies, life expectancy stands invariantly poor. Tumor heterogeneity and its high-grade of invasiveness make it difficult to be surgically resected, and recurrence is inevitable. There is scientific consensus that tumor relapse originates from progenitor/stem-like cells known as glioblastoma stem cells (GSCs) displaying properties of self-renewal and multi-lineage differentiation that contribute to tumor mass heterogeneity. Thus, GSCs represent the target of newly designed therapies. In recent years, it has been highlighted the anti-cancer properties of metformin, the first-line drug in Type-2 diabetes (T2D) treatment. Metformin assumption in T2D patients has been positively linked with a decrease in the risk of several cancer types and cancer-related mortality, including glioblastoma. Additionally, numerous studies demonstrated metformin's anticancer properties against GSCs. Despite metformin's mechanism of action on cancer cells has not been clarified yet, its effect has been proposed to target the oxidative phosphorylation (OXPHOS) pathway. Considering that GSCs have been reported to shuttle between glycolysis and OXPHOS energetic pathways, their metabolic plasticity should prevent the antiproliferative effect of metformin. However, metformin-treated GSCs show a phenotype superimposable to that caused by the blockage of the transmembrane form of the chloride intracellular channel 1 (tmCLIC1). tmCLIC1 involvement in the progression of GB has been assessed deeply in vitro as well as in vivo. In addition, its peculiar localization and enrichment on GSCs' membrane renders it a valuable pharmacological target for GB. Here, we show that in glioblastoma, the transmembrane form of Chloride Intracellular Channel 1 (tmCLIC1) works as a privileged and unique metformin membrane receptor. Nuclear magnetic resonance experiments on live cells confirm the binding to tmCLIC1. Metformin impairs tmCLIC1 activity by a specific binding on a single amino acid, the arginine29. Its mutation demonstrates that metformin-depending tmCLIC1 block is prevented, failing to reduce glioblastoma cells proliferation in 2D and 3D models as well. Moreover, in vivo experiments on zebrafish embryos closely mirror the behavior observed in vitro. Our results demonstrate that tmCLIC1 is essential for metformin antineoplastic effect in glioblastoma and prove a direct binding between the drug and its target. Considering tmCLIC1 contribution to glioblastoma progression, the present work paves the way for future investigations intended to develop a strategy aimed to enhance metformin-tmCLIC1 interaction. Ivan Verduci was supported by a AIRC fellowship for Italy. Citation Format: Ivan Verduci, Francesca Cianci, Riccardo Cazzoli, Gaetano Cannavale, Stefania Castiglione, Matteo Ranucci, Luca Palloni, Beatrice Balboni, Stefania Faletti, Stefania Girotto, Giuliana Pelicci, Saverio Minucci, Alessandro Fantin, Tullio Florio, Michele Mazzanti. Metformin antitumoral activity is exclusively mediated by the membrane functional expression of the Chloride Intracellular Channel 1 in glioblastoma stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 903.

Visfatin: an adipokine that plays a crucial role in increasing the risk of cancer

Obesity is an important public health problem worldwide. Epidemiological studies have demonstrated that obesity is associated with an increased risk of several cancer types. Also, obesity is associated with an increase in cancer mortality. Biological mechanisms and the relationship between obesity and cancer are complex and not well understood. Studies on the role of adiposederived factors in cancer development may be the mechanistic link between obesity and cancer risks. Visfatin or pre-B cell enhancing factor (PBEF) or nicotin-amide-phosphoribosyl-transferase (Nampt) is an important hormone protein that is mainly produced by adipose tissue, and has three major functions: growth factor, cytokine, and nicotinamide phosphoribosyltransferase, therefore, increasing of visfatin has several effects. Recently, studies have shown that over-expression of visfatin is important in the carcinogenesis of several types of cancers. This review aimed to summarize findings from both experimental and epidemiological studies investigating the association between visfatin levels and cancer risk.

Alcohol and Cancer: Epidemiology and Biological Mechanisms.

Approximately 4% of cancers worldwide are caused by alcohol consumption. Drinking alcohol increases the risk of several cancer types, including cancers of the upper aerodigestive tract, liver, colorectum, and breast. In this review, we summarise the epidemiological evidence on alcohol and cancer risk and the mechanistic evidence of alcohol-mediated carcinogenesis. There are several mechanistic pathways by which the consumption of alcohol, as ethanol, is known to cause cancer, though some are still not fully understood. Ethanol’s metabolite acetaldehyde can cause DNA damage and block DNA synthesis and repair, whilst both ethanol and acetaldehyde can disrupt DNA methylation. Ethanol can also induce inflammation and oxidative stress leading to lipid peroxidation and further DNA damage. One-carbon metabolism and folate levels are also impaired by ethanol. Other known mechanisms are discussed. Further understanding of the carcinogenic properties of alcohol and its metabolites will inform future research, but there is already a need for comprehensive alcohol control and cancer prevention strategies to reduce the burden of cancer attributable to alcohol.

863Alcohol and cancer in an Australian cohort of 226,162 participants aged 45 years and over

Abstract Background Australia has a relatively high level of alcohol consumption. Although alcohol consumption is known to increase the risk of several cancer types internationally, local evidence for Australia is limited. Methods Cox proportional hazards regressions were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for cancer risk in relation to weekly alcohol consumption among 226,162 participants aged ≥45 years (2006-2009) in the 45 and Up Study, an Australian prospective cohort study. Incident cancer cases were ascertained by linkage to the New South Wales Cancer Registry to December 2013 by the Centre for Health Record Linkage. Results Over a median 5.4 years, 17,332 cancers were diagnosed. Increasing levels of alcohol intake were associated with increased risk of any cancer (HR per seven drink increase in weekly consumption: 1.02; 95% CI: 1.00-1.04), and cancers of the upper aerodigestive tract (1.19;1.10-1.29), mouth/pharynx (1.18;1.08-1.29), oesophagus (1.22;1.04-1.43), colorectum (1.09;1.04-1.15), colon (1.13;1.06-1.20), liver (1.22;1.04-1.44), breast (1.09;1.00-1.18), and melanoma (1.05;1.00-1.10); whereas an inverse association was observed for thyroid cancer (0.80;0.64-1.00). We estimated that by age 85 years, Australian men and women who consume >14 drinks/week increase their absolute risk of alcohol-attributable cancer by 4.4% and 5.4%, respectively, compared to non-drinkers. Conclusions We report relative risks of cancer incidence in relation to alcohol consumption that match the international evidence. In Australia, a nation with relatively high alcohol consumption, these risks may translate into a significant public health burden. Key messages We have generated estimates for the relationship between alcohol consumption and cancer risk in Australia.

Abstract 752: Neutrophil-to-lymphocyte ratio and subsequent cancer risk in the UK Biobank

Abstract Background: The neutrophil-to-lymphocyte ratio (NLR), a ratio between neutrophil and lymphocyte counts in peripheral blood, is a measure of the balance between systemic levels of inflammation and immunity. NLR has been associated with cancer prognosis, but the role of NLR as a biomarker in carcinogenesis is not well established. Methods: We evaluated 445,443 adults in the UK Biobank, who were aged 37-73 years at baseline, had measured differential blood counts, and were cancer-free and under follow-up 1 year after baseline. NLR was categorized into quartiles. Incident cancers were ascertained from cancer registries. Multivariable Cox regression was used to estimate the per quartile hazard ratio (HR), separately for 69 cancer sites. Models were adjusted for age (quartile), sex, ethnicity (white vs non-white), total WBC (quartile), smoking (never, past, current), alcohol drinking (never, past, current), and BMI (<25, 25-30, ≥30 kg/m2). We present nominally significant results (p<0.05) and also accounting for multiple comparison using a Bonferroni cutoff (p=0.00072). Results: 26,294 incident cancers were diagnosed during a median of 3.3 years of follow-up. The mean NLR in the population was 2.3 (standard deviation 1.2). Increasing NLR quartile was associated with increased risk of cancers in esophagus, colon, lung, soft tissue including heart, uterus, and kidney, but decreased risk of myeloma and chronic lymphocytic leukemia [CLL] (ptrend<0.05). Compared with the lowest NLR quartile, the highest NLR quartile was significantly associated with risk of cancers of the soft tissue including heart (HR 1.98, 95%CI 1.15-3.42), kidney (1.54, 1.22-1.94), uterus (1.39, 1.11-1.73), esophagus (1.27, 0.96-1.69), colon (1.22, 1.06-1.41), myeloma (0.63, 0.47-0.86) and CLL (0.11, 0.02-0.48). After Bonferroni correction, NLR associations remained significant for kidney cancer and CLL. Conclusion: In a comprehensive analysis in a large population-based cohort, NLR was associated with subsequent risk of several cancer types. NLR may reflect the excessive inflammatory status of an individual, even in a subclinical condition, which may promote the development of cancer. On the other hand, low NLR represents a relative rise in the lymphocytes, which may be an indication of circulating premalignant cells for lymphoid malignancies. Citation Format: Minkyo Song, Eric A. Engels. Neutrophil-to-lymphocyte ratio and subsequent cancer risk in the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 752.

Abstract 3079: The antitumoral activity of metformin in glioblastoma stem cells is mediated by tmCLIC1 protein

Abstract Glioblastoma (GB) is the deadliest brain tumor, representing a major clinical challenge in the field. Despite standard of care together with cutting-edge strategies, life expectancy stands invariantly poor. Tumor heterogeneity and its high-grade of invasiveness make it difficult to be surgically resected and recurrence is inevitable. There is scientific consensus that tumor relapse originates from progenitor/stem-like cells known as glioblastoma stem cells (GSCs) displaying properties of self-renewal and multi-lineage differentiation that contribute to tumor mass heterogeneity. Thus, GSCs represent the target of newly designed therapies. In recent years, it has been highlighted the anti-cancer properties of metformin, the first-line drug in Type-2 diabetes (T2D) treatment. Metformin assumption in T2D patients has been positively linked with a decrease in the risk of several cancer types and cancer-related mortality, including glioblastoma. Additionally, numerous studies demonstrated metformin's anticancer properties against GSCs. Despite metformin's mechanism of action on cancer cells has not been clarified yet, its effect has been proposed to target the oxidative phosphorylation (OXPHOS) pathway. Considering that GSCs have been reported to shuttle between glycolysis and OXPHOS energetic pathways, their metabolic plasticity should prevent the antiproliferative effect of metformin. However, metformin-treated GSCs show a phenotype superimposable to that caused by the blockage of the transmembrane form of the chloride intracellular channel 1 (tmCLIC1). tmCLIC1 involvement in the progression of GB has been assessed deeply in vitro as well as in vivo. In addition, its peculiar localization and enrichment on GSCs' membrane renders it a valuable pharmacological target for GB. The goal of the present work is to attest tmCLIC1 as the solely interactor with metformin in glioblastoma stem cells. Ivan Verduci was supported by a AIRC fellowship for Italy. Citation Format: Ivan Verduci, Francesca Cianci, Gaetano Cannavale, Stefania Castiglione, Matteo Ranucci, Michele Mazzanti. The antitumoral activity of metformin in glioblastoma stem cells is mediated by tmCLIC1 protein [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3079.

Obesity is not associated with disease-free interval, melanoma-specific survival, or overall survival in patients with clinical stage IB-II melanoma after SLNB.

Background and ObjectivesClinicopathologic characteristics have prognostic value in clinical stage IB‐II patients with melanoma. Little is known about the prognostic value of obesity that has been associated with an increased risk for several cancer types and worsened prognosis after diagnosis. This study aims to examine effects of obesity on outcome in patients with clinical stage IB‐II melanoma.MethodsProspectively recorded data of patients with clinical stage IB‐II melanoma who underwent sentinel lymph node biopsy (SLNB) between 1995 and 2018 at the University Medical Center of Groningen were collected from medical files and retrospectively analyzed. Cox‐regression analyses were used to determine associations between obesity (body mass index> 30), tumor (location, histology, Breslow‐thickness, ulceration, mitotic rate, SLN‐status) and patient‐related variables (gender, age, and social‐economic‐status [SES]) and disease‐free interval (DFI), melanoma‐specific survival (MSS), and overall survival (OS).ResultsOf the 715 patients, 355 (49.7%) were women, median age was 55 (range 18.6‐89) years, 149 (20.8%) were obese. Obesity did not significantly affect DFI (adjusted hazard ratio [HR] = 1.40; 95% confidence interval [CI] = 0.98–2.00; p = 0.06), MSS (adjusted HR = 1.48;95%CI = 0.97–2.25; p = 0.07), and OS (adjusted HR = 1.25; 95% CI = 0.85–1.85; p = 0.25). Increased age, arm location, increased Breslow‐thickness, ulceration, increased mitotic rate, and positive SLN‐status were significantly associated with decreased DFI, MSS, and OS. Histology, sex, and SES were not associated.ConclusionObesity was not associated with DFI, MSS, or OS in patients with clinical stage IB‐II melanoma who underwent SLNB.

Risk of cancer development in patients with keloids

Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998–2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.

Systematic review with meta-analysis: bariatric surgery reduces the incidence of hepatocellular carcinoma.

Obesity is a risk factor for non-alcoholic steatohepatitis (NASH) and increases the risk of several cancer types including cancers of the liver. Bariatric surgery can provide durable weight loss, but little is known about the later development of hepatocellular carcinoma (HCC) after surgery. To determine whether bariatric surgery reduces the risk of HCC. We performed a comprehensive literature search of major databases (from inception to November 2020) to identify studies which assess the incidence and risk of HCC following bariatric surgery. Pooled data were assessed using a random-effects model expressed in terms of odds ratio (OR), incidence rate ratio and 95% confidence interval (CI). Nine studies (two abstracts and seven full texts) were included for meta-analysis which involved 19514750 patients (18423546 controls and 1091204 bariatric patients). Pooled unadjusted odds ratio (OR) was 0.40 (95% CI: 0.28-0.57) which favoured bariatric surgery, though with high heterogeneity (I2 : 79%). Using an adjusted model derived from matched cohorts (five studies) yielded an OR of 0.63 (95% CI: 0.53-0.75) with moderate heterogeneity (I2 : 38%). The pooled rate/1000 person-years was 0.05 (95% CI: 0.02-0.07) in bariatric surgery patients and 0.34 (95% CI: 0.20-0.49) in the control group with an incidence rate ratio of 0.28 (95% CI: 0.18-0.42). Bariatric surgery is associated with a decreased risk of HCC.

Association between TP53 and MDM2 Gene Polymorphisms and Risk of Hepatocellular Carcinoma in Hepatitis C Virus among Egyptian Populations

Background: The Murine double minute 2 (MDM2) gene is overexpressed in several human tumors. The oncogenic potential of MDM2 is partially explained by inhibition of the activity of the tumor suppressor protein P53 (negative regulator of the P53 tumor suppressor protein). A single nucleotide polymorphism (SNP) in the promoter region of MDM2 gene (T to G exchange at nucleotide 309) and TP53 gene (codon 72 exon 4, rs1042522 encoding either C or G) have been independently associated with increased risk of several cancer types. Few studies have analyzed the role of these polymorphisms in the development of hepatocellular carcinoma among Egyptian patients with chronic hepatitis C virus infection.
 Methods: The study consisted in the comparison of the genotype distribution of TP53 and MDM2 SNP309 in 100 viral hepatitis C-related hepatocellular carcinomas (HCC) cases and 100 controls without HCC matched for age, gender and ethnicity. PCR-RFLP (restriction fragment length polymorphism) and real time PCR methods were used to determine the genotype at the MDM2 SNP309T>G locus and TP53 rs1042522.
 Results: Overall, our results indicate that frequencies of TP53 alleles (C and G) were not significant different between HCC cases and healthy controls (p=0.093) (Odds Ratio, OR=1.361,95% Confidence Interval, 95% CI=0.949 – 1.951). A significant increase of MDM2 SNP309 G/G and T/G genotypes were observed among HCC cases (Odds Ratio, OR=4.868, 95% Confidence Interval, 95% CI= 2.873 – 8.251).
 Conclusions: Our finding suggest that people who have G allele increase the risk by 4.868 folds for developing HCC among Egyptian patients, consequently the MDM2 309T>G polymorphism is an important modulator of hepatocellular carcinoma development in Egyptian patients.

Polyphenol Intake and Gastric Cancer Risk: Findings from the Stomach Cancer Pooling Project (StoP).

Simple SummaryGastric cancer (GC) has the fifth highest incidence of any cancer type worldwide and the third highest mortality rate, so its prevention is very important. Among dietary factors, the consumption of fruit and vegetables has been inversely related to GC risk. Phenolic compounds may exert a favorable effect on the risk of several cancer types, including gastric cancer. However, selected polyphenol classes have not been adequately investigated in relation to GC. There is, however, no comprehensive analysis of polyphenols and GC risk methods to date. In order to provide a detailed evaluation of the relationship between dietary intake of polyphenols and GC risk, we analyzed data from the Stomach cancer Pooling (StoP) Project consortium.Phenolic compounds may exert a favorable effect on the risk of several cancer types, including gastric cancer (GC). However, selected polyphenol classes have not been adequately investigated in relation to GC. The aim of this study is to evaluate the association between the intake of polyphenols in relation to GC risk. We used data from the Stomach cancer Pooling (StoP) Project, including 10 studies from six countries (3471 GC cases and 8344 controls). We carried out an individual participant data pooled analysis using a two-stage approach. The summary odds ratios (ORs) of GC for each compound, and the corresponding 95% confidence intervals (95% CI), were computed by pooling study specific ORs obtained through multivariate logistic regression, using random effect models. Inverse associations with GC emerged for total polyphenols (OR = 0.67, 95% CI = 0.54–0.81, for the highest versus lowest quartile of intake), total flavonoids (OR = 0.73, 95% CI = 0.55–0.90), anthocyanidins (OR = 0.74, 95% CI = 0.56–0.92), flavanols (OR = 0.77, 95% CI = 0.66–0.88), flavanones (OR = 0.57, 95%CI = 0.44–0.69), total phenolic acids (OR = 0.75, 95%CI = 0.55–0.94), and hydroxybenzoic acids (OR = 0.73, 95%CI = 0.57–0.89). Results were consistent across strata of age, sex, social class, and smoking habit. Suggestive inverse associations were also found for flavonols (OR = 0.76, 95%CI = 0.51–1.01) and hydroxycinnamic acids (OR = 0.82, 95%CI = 0.58–1.06). Further investigations from longitudinal data are needed to confirm this association.

Characterization of Surface Receptor Expression and Cytotoxicity of Human NK Cells and NK Cell Subsets in Overweight and Obese Humans.

Obesity is associated with an increased risk for several cancer types and an altered phenotype and functionality of natural killer (NK) cells. This study aimed to investigate the association of overweight and obesity with NK cell functions and receptor expression profiles in humans. Therefore, peripheral blood mononuclear cells were isolated from normal weight, overweight, and obese healthy blood donors. In depth analysis of immune cell populations and 23 different surface markers, including NK cell receptors, NK-cell-related markers as well as functional intracellular markers on total NK cells and NK subgroups were performed by multicolor flow cytometry. The data revealed a decreased expression of the activating NK cell receptors KIR2DS4 and NKp46 as well as an increased expression of the inhibitory NK cell receptors NKG2A and Siglec-7 in overweight and obese compared to normal weight individuals. Additionally, the expression of the adhesion molecule CD62L and the maturation and differentiation marker CD27 was downregulated in NK cells of overweight and obese subjects. Furthermore, the cytotoxicity of NK cells against colorectal cancer cells was decreased in overweight and obese subjects. Investigations on underlying killing mechanisms demonstrated a reduced TRAIL expression on NK cells of obese subjects suggesting an impaired death receptor pathway in obesity. The present study gives new insights into an impaired functionality and phenotype of NK cells and NK cell subsets in overweight and obesity. These phenotypic alterations and dysfunction of NK cells might be an explanation for the increased cancer risk in obesity.

Abstract 4641: Association between dietary tomato intake and the risk of hepatocellular carcinoma: Findings from a prospective cohort study

Abstract Background: Intake of tomato and/or lycopene have been found to be associated with reduced risk of several cancer types, but epidemiological data on risk of hepatocellular carcinoma (HCC) are sparse. Methods: The associations of tomato and lycopene consumption with risk of HCC were examined in the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women aged 45-74 years at enrollment in 1993-1998 with 25 years of follow-up. Tomato and lycopene consumption was evaluated using a validated semi-quantitative food frequency questionnaire. Incident HCC cases were ascertained through the linkage analysis with the nationwide Singapore cancer registry. Cox proportional hazard regression was used to estimate hazard ratio (HR) and its 95% confidence interval (CI) of HCC with the consumption of tomato and lycopene among all cohort participants, and unconditional logistic regression was used to assess the association among individuals negative for hepatitis B surface antigen (HBsAg). Results: After a mean follow-up of 17.6 years, 561 incident HCC cases were identified. Higher tomato intake was associated with lower risk of HCC after adjustment for multiple potential confounders (Ptrend<0.001). Compared to the lowest quartile, HRs (95% CIs) of HCC for the 2nd, 3rd, and 4th quartile of tomato intake were 0.70 (0.56-0.88), 0.73 (0.58-0.92), and 0.63 (0.49-0.81). Among HBsAg-negative individuals, the inverse association remained (Ptrend=0.03). There was no association between lycopene intake and HCC risk (Ptrend=0.54). Conclusion: Tomato intake may offer protection against the development of HCC, particularly among individuals without chronic infection with hepatitis B virus. Citation Format: Claire E. Thomas, Hung N. Luu, Renwei Wang, Jennifer Adams-Haduch, Jian-Min Yuan, Aizhen Jin, Woon-Puay Koh. Association between dietary tomato intake and the risk of hepatocellular carcinoma: Findings from a prospective cohort study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4641.

Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms

Telomere length measured in leukocyte (LTL) has been found to be associated with the risk of developing several cancer types, including myeloproliferative neoplasms (MPNs). LTL is genetically determined by, at least, 11 SNPs previously shown to influence LTL. Their combination in a score has been used as a genetic instrument to measure LTL and evaluate the causative association between LTL and the risk of several cancer types. We tested, for the first time, the “teloscore” in 480 MPN patients and 909 healthy controls in a European multi-center case–control study. We found an increased risk to develop MPNs with longer genetically determined telomeres (OR = 1.82, 95% CI 1.24–2.68, P = 2.21 × 10−3, comparing the highest with the lowest quintile of the teloscore distribution). Analyzing the SNPs individually we confirm the association between TERT-rs2736100-C allele and increased risk of developing MPNs and we report a novel association of the OBFC1-rs9420907-C variant with higher MPN risk (ORallelic = 1.43; 95% CI 1.15–1.77; P = 1.35 × 10−3). Consistently with the results obtained with the teloscore, both risk alleles are also associated with longer LTL. In conclusion, our results suggest that genetically determined longer telomeres could be a risk marker for MPN development.

Work Conditions and Practices in Norwegian Fire Departments From 1950 Until Today: A Survey on Factors Potentially Influencing Carcinogen Exposure.

BackgroundMeta-analyses have shown firefighters to be at an increased risk of several cancer types. Occupational carcinogen exposure may explain these increased risks. This study aims to describe Norwegian fire departments' work conditions from 1950 until today, focusing on factors relevant for potential occupational carcinogen exposure.MethodsWith the help of a reference group, we developed a questionnaire on topics related to occupational exposure to carcinogens for the period 1950–2018. Selected Norwegian fire departments provided department-specific responses.ResultsSixteen departments, providing fire services for 48% of the Norwegian population as of 2019 and mainly consisting of professional firefighters, responded to our questionnaire. The introduction of synthetic firefighting foams, more regular live fire training, the introduction of chemical diving, and a higher number of diesel-driven fire service vehicles were identified as changes thought to increase exposure to occupational carcinogens. Changes thought to decrease exposure included the switch from negative to positive pressure self-contained breathing apparatuses, the use of self-contained breathing apparatuses during all phases of firefighting, the use of ventilating fans during firefighting, increased attention to flammable materials used during live fire training, increased attention to handling and cleaning of turnout gear and other equipment, and installment of exhaust removal systems in apparatus bays.ConclusionNorwegian fire departments' work conditions have seen several changes since 1950, and this could influence firefighters' occupational carcinogen exposure. A peak of carcinogen exposure may have occurred in the 1970s and 1980s before recent changes have reduced exposure.

Alcohol Drinking and Bladder Cancer Risk From a Pooled Analysis of Ten Cohort Studies in Japan.

BackgroundThe association of alcohol drinking with bladder cancer risk remains unclear in East Asian populations. Aldehyde dehydrogenase 2 (ALDH2) enzyme oxidizes alcohol-metabolized carcinogenic acetaldehyde into acetate. It is well known that the inactive ALDH2 carriers, specific to East Asian populations, have an increased risk of several cancer types because of increased exposure to acetaldehyde after alcohol consumption. The aim of this study was to examine the association between alcohol drinking and bladder cancer risk using data from ten population-based prospective cohort studies in Japan, where approximately 40% of the population has inactive ALDH2 enzyme.MethodsWe analyzed 340,497 Japanese participants with average follow-up of 13.4 years. The association between alcohol drinking and bladder cancer risk was evaluated using Cox regression models within each study, and random-effects models were used to estimate pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs).ResultsDuring 4,729,071 person-years, 936 men and 325 women were newly diagnosed with bladder cancer. Our results showed no evidence of significant association between alcohol drinking and bladder cancer risk even among men who consumed alcohol of ≥69 g/week, with HR of 1.02 (95% CI, 0.79–1.33). The null result was observed consistently among women.ConclusionsOur findings do not support an association between alcohol drinking and bladder cancer risk in the Japanese, at least without consideration of the polymorphisms of alcohol-metabolizing enzymes.

Awareness of alcohol as a risk factor for cancer: A population-based cross-sectional study among 3000 Danish men and women.

Alcohol increases the risk of several cancer types. However, awareness of the link between alcohol and cancer is estimated to be low in Denmark. The objective of this study was to examine awareness of alcohol as a risk factor for cancer in the Danish population. 3000 Danish men and women aged 18–74 years, who are nationally representative participated in a cross-sectional study. Open and closed-ended questions were used to assess unprompted and prompted cancer awareness in relation to the respondents’ demographic profile, alcohol consumption and use of tobacco.Unprompted, 22.2% of respondents were aware of the link between alcohol and cancer, whereas prompted 44.8% were aware of this. When prompted about specific cancer types, 39.5% were aware of the fact that alcohol increases the risk of liver cancer and only 9.6% were aware of the link between alcohol and breast cancer. Being aware of the link between alcohol and cancer was associated with being female, having a higher level of education, living in the Capital Region of Denmark, as well as being a non-smoker. There were no statistical significant associations between awareness of alcohol as a risk factor for cancer and the respondents’ age, marital status and alcohol consumption.Conclusively, the study confirms a rather low public awareness of the link between alcohol and cancer in the Danish population, especially regarding certain cancer types such as breast cancer. There is a continued need to inform the public about the relationship between alcohol and cancer.

The Mediterranean Diet as source of bioactive compounds with multi-targeting anti-cancer profile

Many bioactive agents have been extracted from plants or belong to functional foods and have been considered in the treatment of serious and multifactorial diseases, such as cancer. In particular, this review is focused on the anti-cancer properties owned by several natural products typically from the Mediterranean area. In some regions of the South of Italy, a lower cancer incidence has been observed. There is increasing evidence that adherence to a Mediterranean dietary pattern correlates with reduced risk of several cancer types. This could be mainly attributed to the typical lifestyle aspects of the Mediterranean diet, such as high consumption of fruit and vegetables. In this review, the main natural products of the Mediterranean area are discussed, with particular attention on their anti-cancer properties endowed with multi-target profiles.