Modify Cancer Risk Research Articles

The Role of Single Nucleotide Polymorphisms in MicroRNA Genes in Head and Neck Squamous Cell Carcinomas: Susceptibility and Prognosis.

Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent cancers worldwide. The identification of molecular alterations adding to the individual risk of HNSCC development and progression is one of the most important challenges in studies on cancer genetics. MicroRNAs (miRNAs), which belong to the group of important post-transcriptional regulators of human gene expression, seem to be valuable options for consideration as key modifiers of individual cancer risk, and therefore may be helpful in predicting inter-individual differences in cancer risk, response to treatment and prognosis. There have not been many studies focused on the relationship between miRNA variants and HNSCC published in PubMed within the last 15 years. We found and analyzed 30 reviews, meta-analyses and research papers and revealed 14 SNPs which have been reported as significant in the context of HNSCC susceptibility and/or prognosis. These 14 SNPs were located in 13 separate miRNAs. Among them, four were the most frequently studied (miRNA-146, -196, -149 and -499) and have been shown to have the greatest impact on the course of HNSCC. However, the presented results have been conflicting. It must be concluded that, despite the years of studies, there are no conclusive reports demonstrating a significant role of SNPs in miRNAs in the context of the susceptibility to HNSCC or its prognosis.

The Clinical Impact of Time-restricted Eating on Cancer: A Systematic Review.

In the face of the growing global burden of cancer, there is increasing interest in dietary interventions to mitigate its impacts. Pre-clinical evidence suggests that time-restricted eating (TRE), a type of intermittent fasting, induces metabolic effects and alterations in the gut microbiome that may impede carcinogenesis. Research on TRE in cancer has progressed to human studies, but the evidence has yet to be synthesized. The objective of this study was to systematically evaluate the clinical and/or metabolomic effects of TRE compared with ad libitum eating or alternative diets in people with cancer. Ovid MEDLINE, Ovid Embase, CINAHL, Ovid Cochrane Central Register of Control Trials (CENTRAL), Web of Science Core Collection (ESCI, CPCI-SSH, CPCI-S), and SCOPUS were searched up to January 4, 2023, using the core concepts of "intermittent fasting" and "cancer." Original study designs, protocols, and clinical trial registries were included. After evaluating 13 900 results, 24 entries were included, consisting of 8 full articles, 2 abstracts, 1 published protocol and 13 trial registries. All data were extracted, compared, and critically analyzed. There was heterogeneity in the patient population (eg, in tumor sites), TRE regimens (eg, degree of restriction, duration), and clinical end points. A high rate (67-98%) of TRE adherence was observed, alongside improvements in quality of life. Four articles assessed cancer markers and found a reduction in tumor marker carcinoembryonic antigen, reduced rates of recurrence, and a sustained major molecular response, following TRE. Five articles demonstrated modified cancer risk factors, including beneficial effects on body mass index, adiposity, glucoregulation, and inflammation in as short a period as 8 weeks. None of the completed studies assessed the effect of TRE on the microbiome, but analysis of the microbiome is a planned outcome in 2 clinical trials. Preliminary findings suggest that TRE is feasible and acceptable by people with cancer, may have oncological benefits, and improves quality of life. PROSPERO registration No. CRD42023386885.

Differences in modifiable cancer risk behaviors by nativity (US-born v. Non-US-born) and length of time in the US.

Previous studies have identified racial-ethnic disparities in modifiable risk factors for cancers. However, the impact of US nativity on these risks is understudied. Hence, we assessed the association between US nativity and length of time in the US on modifiable cancer risk factors. Utilizing the 2010 and 2015 National Health Interview Survey datasets, we analyzed 8,861 US-born and non-US-born adults. Key variables included age, sex, race-ethnicity, education, income, diet, body mass index, physical activity, alcohol consumption, and smoking. Statistical methods included descriptive statistics and regression. Most respondents were US-born (n = 7,370), followed by long-term (≥15 years, n = 928), and recent (<15 years, n = 563) immigrants. Moderate-to-vigorous physical activity was higher among US-born individuals (342.45 minutes/week), compared to recent (249.74 minutes/week) and long-term immigrants (255.19 minutes/week). Recent immigrants consumed more fruits (1.37 cups/day) and long-term immigrants more vegetables (1.78 cups/day) than US-born individuals. Multivariate analyses found recent immigrants had lower odds of consuming alcohol (AOR: 0.33, 95% CI: 0.21-0.50) and smoking (AOR: 0.30, 95% CI: 0.19-0.46), and higher odds of meeting fruit consumption guidelines (AOR: 2.80, 95% CI: 1.76-4.45) compared to US-born individuals. Long-term immigrants had lower odds of alcohol consumption (AOR: 0.56, 95% CI: 0.37-0.84) and smoking (AOR: 0.42, 95% CI: 0.30-0.59), and higher odds for meeting fruit (AOR: 1.87, 95% CI: 1.22-2.86) and fiber (AOR: 2.03, 95% CI: 1.02-4.05) consumption guidelines. Our findings illustrate the importance of considering the impact nativity and length of US residency has on health. Our findings underscore the need for culturally tailored public health strategies.

An oncogenic enhancer promotes melanoma progression via regulating ETV4 expression

BackgroundEnhancers are important gene regulatory elements that promote the expression of critical genes in development and disease. Aberrant enhancer can modulate cancer risk and activate oncogenes that lead to the occurrence of various cancers. However, the underlying mechanism of most enhancers in cancer remains unclear. Here, we aim to explore the function and mechanism of a crucial enhancer in melanoma.MethodsMulti-omics data were applied to identify an enhancer (enh17) involved in melanoma progression. To evaluate the function of enh17, CRISPR/Cas9 technology were applied to knockout enh17 in melanoma cell line A375. RNA-seq, ChIP-seq and Hi-C data analysis integrated with luciferase reporter assay were performed to identify the potential target gene of enh17. Functional experiments were conducted to further validate the function of the target gene ETV4. Multi-omics data integrated with CUT&Tag sequencing were performed to validate the binding profile of the inferred transcription factor STAT3.ResultsAn enhancer, named enh17 here, was found to be aberrantly activated and involved in melanoma progression. CRISPR/Cas9-mediated deletion of enh17 inhibited cell proliferation, migration, and tumor growth of melanoma both in vitro and in vivo. Mechanistically, we identified ETV4 as a target gene regulated by enh17, and functional experiments further support ETV4 as a target gene that is involved in cancer-associated phenotypes. In addition, STAT3 acts as a transcription factor binding with enh17 to regulate the transcription of ETV4.ConclusionsOur findings revealed that enh17 plays an oncogenic role and promotes tumor progression in melanoma, and its transcriptional regulatory mechanisms were fully elucidated, which may open a promising window for melanoma prevention and treatment.

Association between Metabolic-Dysfunction-Associated Steatotic Liver Disease and Hepatic Cancer: Current Concepts and Future Challenges.

Background: This study systematically reviewed the association between metabolic-dysfunction-associated steatotic liver disease (MASLD) and the development of hepatic cancer. Previous research has highlighted MASLD as a predisposing condition. Aim: To collect recent global data on the relationship between MASLD and hepatic cancer. Methods: A systematic review was conducted, which included an analysis of studies on the relationship between MASLD and the incidence of hepatic cancers, focusing on the role of fibrosis and MASLD severity as predictors of cancer risk. Following standard methodological frameworks for the assessment of longitudinal studies, the review gathered information on fibrosis scores, hepatocellular carcinoma (HCC) incidence, and other types of hepatic neoplasms. Results: A total of 522 studies were initially identified, of which 6 studies were appropriate for the review. They collectively revealed that the stage of fibrosis in MASLD is a significant independent predictor of mortality and liver-related events, with higher fibrosis stages correlating with greater risk. Longitudinal data showed that increases in FIB-4 scores were linked to a higher risk of developing HCC and cirrhosis. MASLD was also associated with an increased risk of non-hepatic cancers such as colorectal cancer in males and breast cancer in females. The severity of MASLD was found to be a modifiable risk factor for biliary tract cancer (BTC), with the risk further amplified by diabetes. Moreover, lifestyle factors and comorbidities, such as smoking and diabetes, were identified as modifiers of cancer risk in MASLD patients. Conclusions: The systematic review identified the association between MASLD and an elevated risk of hepatic cancer, establishing a clear link between the severity of liver fibrosis and the incidence of HCC and other hepatic neoplasms. This supports the need for screening for hepatic cancer in patients with MASLD, particularly in the presence of advanced fibrosis or other risk-modifying factors.

Abstract 4291: Bai1 inhibition promotes ferroptosis of breast cancer cells to prevent tumor growth in human xenograft tumor models

Abstract The adhesion G-protein coupled- receptor 1 ADGRB1/Bai1 was identified as a phosphatidylserine receptor that cooperates with ELMO/Dock180/Rac to promote maximal engulfment of apoptotic cells. This function of Bai1 was also shown to promote myoblasts fusion. Cell-cell fusion has been demonstrated to occur in normal physiological functions as well as in diseases. Studies have shown in cancer that cell-cell fusion increases tumor heterogeneity, drug resistance, and metastasis as hybrids acquire new properties that allow them to migrate and proliferate at new sites. Activation of ELMO-Dock signaling pathway has been associated with breast cancer metastasis. Moreover, ELMO1 has been identified as a modifier of breast cancer risk for BRCA mutation carriers. Rac1 was also shown to be overexpressed in proliferative breast disease, preinvasive and invasive breast carcinoma as well as lymph node metastases. Our recent studies showed that breast cancer cell fusion with bone marrow-derived mesenchymal stem cells was modulated by hypoxic conditions and promoted by apoptosis. Our hypothesis is that hypoxia stress induced apoptosis activates the phosphatidylserine receptor Bai1, and it signals through the ELMO/DOCK180/Rac to promote breast cancer cell fusion-driven tumor heterogeneity and metastasis. In this study, we determined the ability of Bai1 depleted breast cancer cells to induce tumor growth in immunocompromised mice. We used Bai1 sgRNA to inhibit Bai1 expression in the breast cancer cell MDA-MB-231. These cells (1x 106) together with bone marrow-derived mesenchymal stem cells (MSCs) (1x 106) were injected into the fat pad of the breast of 15 NOD SCID female mice. Control mice (15) received the same cells with no inhibition of Bai1. The mice were monitored for eight weeks. We found that Bai1 inhibition significantly reduced tumor growth in these mice in the course of time (P&amp;lt;0.05). The average tumor weight was also significantly reduced when Bai1 was inhibited (P&amp;lt;0.001). RNA sequencing of tumors generated from these mice revealed a significant increase in the expression of genes driving ferroptosis and a reduction in critical oncogenes in the experiment group compared to the control group. These findings will be helpful in the development of new classes of drugs effective in breast cancer treatment. Grant Support The NIH/NIMHD grant 5U54MD015929-03, the Society for Investigative Dermatology (SID) Freinkel Diversity Fellowship, and NSF Award Notice for Award ID 2142465 (awarded to FNK). Citation Format: Felicite Kamdem Noubissi, Oluwatowin Odubanjo, Hung-Chung Huang, Brenda Ogle, Paul Tchounwou. Bai1 inhibition promotes ferroptosis of breast cancer cells to prevent tumor growth in human xenograft tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4291.

Abstract 283: Fibroblast diversity and immune microenvironment in pseudoangiomatous stromal hyperplasia (PASH): Associations with breast cancer risk

Abstract Benign breast disease (BBD) affects over one million women annually in the United States and is diagnosed in nearly half of all women during their lifetime. Pseudoangiomatous stromal hyperplasia (PASH), a common BBD subtype, is characterized by an overaccumulation of tissue fibroblasts. Current research suggests a pivotal role of the immune microenvironment in progression of BBD to breast cancer, suggesting its composition as a determinant of breast cancer risk. Our study evaluates whether fibroblast variations and immune microenvironment differences in BBD biopsies containing PASH lesions are associated with subsequent breast cancer development. We evaluated BBD biopsies from women who subsequently developed breast cancer (cases, N=5) or remained cancer-free (controls, N=5). Using Opal-based multiplex immunofluorescence (mIF) assays, we mapped expression of fibroblast markers linked to breast cancer associated fibroblasts (CAFs), including vimentin (VIM), smooth muscle actin (ACTA2), fibroblast specific protein-1 (S100A4/FSP1), fibroblast associated protein (FAP), integrin beta-1 (CD29/ITGB1), and platelet derived growth factor receptor beta (PDGFRβ) and markers of key immune cells (T cells: CD4, CD8; dendritic cells: CD11c; B cells: CD20; and macrophages: CD68) along with MKI67 as a proliferation marker. Our results revealed marked differences in fibroblast marker expression and immune cell populations between these groups in the normal lobules in the BBD biopsies. PASH cases showed elevated PDGFRβ and CD29/ITGB1 expression in VIM-positive fibroblasts, markers characteristic of CAF subtypes known to accumulate in more aggressive tumor microenvironments. Conversely, a higher percentage of FSP1+/VIM+ cells, similar to that of a different CAF subtype, was noted in the lobules of PASH controls. This difference in biomarker expression, along with corresponding variations in immune cell counts, suggests a complex interplay between fibroblast composition and immune response that ultimately modulate cancer risk in PASH-containing BBD tissues. Additionally, increased MKI67 expression in PASH cases potentially signals the higher likelihood of cancer development. This work advances our understanding of fibroblast heterogeneity in BBD and its implications for breast cancer risk and progression, and paves the way for innovative strategies to improve clinical outcomes for BBD patients to reduce their incidence of breast cancer. Citation Format: Nicole Cruz-Reyes, Matilde Rossi, Melody Stallings Mann, Bryan McCauley, Tanya Hoskin, Robert Vierkant, Stacey Winham, Amy Degnim, Mark E. Sherman, Derek C. Radisky. Fibroblast diversity and immune microenvironment in pseudoangiomatous stromal hyperplasia (PASH): Associations with breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 283.

A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study

Alternative polyadenylation plays an important role in cancer initiation and progression; however, current transcriptome-wide association studies mostly ignore alternative polyadenylation when identifying putative cancer susceptibility genes. Here, we perform a pan-cancer 3′ untranslated region alternative polyadenylation transcriptome-wide association analysis by integrating 55 well-powered (n > 50,000) genome-wide association studies datasets across 22 major cancer types with alternative polyadenylation quantification from 23,955 RNA sequencing samples across 7,574 individuals. We find that genetic variants associated with alternative polyadenylation are co-localized with 28.57% of cancer loci and contribute a significant portion of cancer heritability. We further identify 642 significant cancer susceptibility genes predicted to modulate cancer risk via alternative polyadenylation, 62.46% of which have been overlooked by traditional expression- and splicing- studies. As proof of principle validation, we show that alternative alleles facilitate 3′ untranslated region lengthening of CRLS1 gene leading to increased protein abundance and promoted proliferation of breast cancer cells. Together, our study highlights the significant role of alternative polyadenylation in discovering new cancer susceptibility genes and provides a strong foundational framework for enhancing our understanding of the etiology underlying human cancers.

Hyperthyroidism and the risk of non-thyroid cancer: a Danish register-based long-term follow-up study.

Cancer is the second most common cause of death worldwide. It is currently debated whether thyroid dysfunction is a modifiable cancer risk factor. Our aim was to evaluate the risk of cancer in patients with hyperthyroidism. This is a register-based nationwide cohort study of individuals with a diagnosis of hyperthyroidism. Each hyperthyroid case was matched with four reference individuals according to age and sex. Using Fine and Gray competing risk regression models, we studied the association of hyperthyroidism and subsequent all-cause cancer diagnoses, adjusted for preexisting morbidity. Sub-analyses were stratified for cause of hyperthyroidism (Graves' disease and toxic nodular goiter, age when diagnosed with hyperthyroidism, sex, and cancer localization (lung, prostate, breast, and colorectal cancer)). The cohort consisted of 95,469 patients with hyperthyroidism (followed for a median of 10.9 years (range: 5.2-17.2)), and 364,494 reference individuals (followed for a median of 11.2 years (range: 5.4-17.4)). Hyperthyroidism was associated with increased all-cause cancer risk (sub-distribution hazard ratio (SHR): 1.12; 95% CI: 1.10-1.14), as well as an increased risk of breast (SHR: 1.07; 95% CI: 1.02-1.13), lung (SHR: 1.20; 95% CI: 1.16-1.26), and prostate cancer (SHR: 1.10; 95% CI: 1.02-1.19), but not colorectal cancer (SHR: 1.04; 95% CI: 0.99-1.09). Sub-analyses stratified for age when diagnosed with hyperthyroidism and cause of hyperthyroidism yielded similar results. In this register-based study, patients with hyperthyroidism had an increased risk of cancer, in particular lung, prostate, and breast cancer. Whether a causal link exists remains to be proven.

DNA damage response alterations in clear cell renal cell carcinoma: clinical, molecular, and prognostic implications

BackgroundDNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic responses. Nonetheless, the characteristics and significance of DDR alterations in clear cell renal cell carcinoma (ccRCC) remain undefined. This study aimed to explore the predictive role, molecular mechanism, and tumor immune profile of DDR genes in ccRCC.MethodsWe prospectively sequenced 757 tumors and matched blood DNA samples from Chinese patients with ccRCC using next-generation sequencing (NGS) and analyzed data from 537 patients from The Cancer Genome Atlas (TCGA). A comprehensive analysis was performed.ResultsFifty-two percent of Chinese patients with ccRCC harbored DDR gene mutations and 57% of TCGA patients. The immunotherapy treatment prognosis of patients with DDR gene mutations was superior to that of patients without DDR gene mutations (p = 0.047). DDR gene mutations were associated with more gene mutations and a higher tumor mutation load (TMB, p < 0.001). Moreover, patients with DDR gene mutations have a distinct mutational signature compared with those with wild-type DDR. Furthermore, the DDR-mut group had elevated neoantigen load (including single-nucleotide variants (SNV) and indel neoantigen load, p = 0.037 and p = 0.002, respectively), TCR Shannon (p = 0.025), and neutrophils (p = 0.010). DDR gene mutations exhibited a distinct immune profile with significantly higher expression levels of TNFSF9, CD70, ICAM1, and indoleamine-2,3-dioxygenase (IDO) and lower expression levels of VTCN1 and IL12A.ConclusionsOur data suggest that the detection of somatic mutations in DDR genes can predict the efficacy of immunotherapy in patients with ccRCC. Furthermore, we revealed the unique molecular and immune mechanisms underlying ccRCC with DDR gene mutations.

Utilizing Human Genetics to Develop Chemoprevention for Cancer-Too Good an Opportunity to be Missed.

Large-scale genetic studies are reliably identifying many risk factors for disease in the general population. Several of these genetic risk factors encode potential drug targets, and genetics has already helped to introduce targeted agents for some diseases, an example being lipid-lowering drugs to reduce the incidence of cardiovascular disease. Multiple drugs have been developed to treat cancers based on somatic mutations and genomics, but in stark contrast, there seems to be a reluctance to use germline genetic data to develop drugs to prevent malignancy, despite the large numbers of people who could benefit, the potential for lowering cancer rates, and the widespread current use of non-pharmaceutical measures to reduce cancer risk factors such as tobacco, alcohol, and infectious diseases. We argue that concerted efforts for cancer prevention based on genetics, including genes influenced by common polymorphisms that modulate cancer risk, are urgently needed. There are enormous, yet underutilized, opportunities to develop novel targeted agents for chemoprevention of cancer based on human germline genetics. Such efforts are likely to require the support of a dedicated funding program by national and international agencies. See related commentary by Winham and Sherman, p. 13.

Introduction to Nutrition and Cancer.

By the beginning of the year 2021, the estimated number of new cancer cases worldwide was about 19.3 million and there were 10.0 million cancer-related deaths. Cancer is one of the deadliest diseases worldwide that can be attributed to genetic and environmental factors, including nutrition. The good nutrition concept focuses on the dietary requirements to sustain life. There is a substantial amount of evidence suggesting that a healthy diet can modulate cancer risk, particularly the risk of colorectal and breast cancers. Many studies have evaluated the correlation between our diet and the risk of cancer development, prevention, and treatment. The effect of diet on cancer development is likely to happen through intertwining mechanisms including inflammation and immune responses. For instance, a greater intake of red and processed meat along with low consumption of fruits and vegetables has been associated with increased levels of inflammatory biomarkers that are implicated in cancer development. On the other hand, the consumption of phytosterols, vitamins, and minerals, which exert antioxidant and anti-inflammatory roles have been linked to lower cancer risk, or even its occurrence prevention. In this book, we aim to summarize the current knowledge on the role of nutrition in cancer to provide the best scientific advice in this regard.

Every tenth malignant solid tumor attributed to overweight and alcohol consumption: A population-based cohort study

BackgroundRecent studies have shown that some four in ten cancers are attributable to a few key risk factors. The aim of this study was to estimate cohort-based population attributable fractions (PAFs) in Finland for potentially modifiable cancer risk factors. MethodsData from eight health studies including 253,953 subjects with 29,802 incident malignant solid tumors were analysed using Bayesian multivariate regression model with multiplicative risk factor effects. We estimated the effects of smoking, excess body weight, alcohol consumption, physical activity, parity and education on cancer incidence and related PAFs by cancer site, accounting for competing mortality. ResultsPAF for all cancer sites and exposures combined was 34% (95% credible interval 29%−39%) in men and 24% (19%−28%) in women. In men, 23% (21%−27%) and in women 8% (6%−9%) of all cancers were attributed to smoking. PAF related to excess body weight was 4% (2%−6%) in men and 5% (2%−7%) in women, to alcohol 7% (3%−10%) in men and 4% (0%−7%) in women, and to excess body weight and alcohol combined 10% (6%−15%) in men and 9% (4%−13%) in women. ConclusionSmoking was the most important factor contributing to cancer burden in Finnish men and women over the last 40 years. The contribution of excess body weight and alcohol consumption together outweighed the role of smoking in women. As the prevalence of overweight is expected to increase, more efficient public health measures supporting adherence to healthy weight are essential to reduce cancer burden.

Research on Rare Diseases in Germany - The cancer predisposition syndrome registry.

Cancer predisposition syndromes (CPS) are rare diseases that are associated with an increased risk of cancer due to genetic alterations. At least 8 % of all cases of childhood cancer are attributable to CPS [1, 2]. The CPS registry was launched in 2017 to learn more about CPS and to improve the care to those afflicted by these diseases. This is an internationally networked registry with associated accompanying studies that investigate cancer risks and spectra, the possibilities of cancer prevention, early detection and therapy. For several of these syndromes, new insights into the cancer risks and cancer types as well as factors modifying cancer risk have been gained. In addition, experimental, psycho-oncological, preclinical and clinical studies were initiated. The CPS registry is an example of how progress can be made within a short period of time to the benefit of individuals with rare diseases through systematic data collection and research.

Modification of incident cancer risk with changes in metabolic syndrome status: A prospective cohort study in Taiwan

PurposeWe aimed to investigate the effect of altered metabolic syndrome (MetS) status on cancer risk. MethodsFrom 2002 through 2008 of the Taiwan MJ cohort, there were 111,616 adults who had repeated MetS measurements performed 3.3 years apart and were followed up for cancer incidence over 11.8 years. Cancer was confirmed based on histopathological reports. ResultsParticipants were categorized as MetS-free (n = 80,409; no MetS at the first or last health screening), MetS-developed (n = 9833; MetS absence at the first screening and presence at the last screening), MetS-recovered (n = 8958; MetS presence at the first screening and absence at the last screening), and MetS-persisted (n = 12,416; MetS presence at the first and last screenings). We used the Fine-Gray sub-distribution method, with death as competing risk, to determine the association between MetS changes and incident cancer risk. During 1320,796 person-years of follow-up, 5862 individuals developed cancer. The incidence rate of cancer per 1000 person-years was 3.89 in the MetS-free, 5.26 in MetS-developed, 4.61 in MetS-recovered, and 7.33 in MetS-persisted groups (P < .001). Compared with the MetS-free group, MetS-persisted individuals had a higher risk of incident cancer. ConclusionsPersistent MetS was found to be associated with a high risk of incident cancer.

International burden of cancer deaths and years of life lost from cancer attributable to four major risk factors: a population-based study in Brazil, Russia, India, China, South Africa, the United Kingdom, and United States

We provide a comprehensive view of the impact of alcohol consumption, tobacco smoking, excess body weight, and human papillomavirus (HPV) infection on cancer mortality and years of life lost (YLLs) in Brazil, Russia, India, China, South Africa, the United Kingdom (UK), and United States (US). We collected population attributable fractions of the four risk factors from global population-based studies and applied these to estimates of cancer deaths in 2020 to obtain potentially preventable cancer deaths and their 95% confidence intervals (CIs). Using life tables, we calculated the number and age-standardised rates of YLLs (ASYR). In Brazil, Russia, India, China, South Africa, the UK, and the US in 2020, an estimated 5.9 million (3.3 million-8.6 million) YLLs from cancer were attributable to alcohol consumption, 20.8 million (17.0 million-24.6 million) YLLs to tobacco smoking, 3.1 million (2.4 million-3.8 million) YLLs to excess body weight, and 4.0 million (3.9 million-4.2 million) YLLs to HPV infection. The ASYR from cancer due to alcohol consumption was highest in China (351.4 YLLs per 100,000 population [95% CI 194.5-519.2]) and lowest in the US (113.5 [69.6-157.1]) and India (115.4 [49.7-172.7). For tobacco smoking, China (1159.9 [950.6-1361.8]) had the highest ASYR followed by Russia (996.8 [831.0-1154.5). For excess body weight, Russia and the US had the highest ASYRs (385.1 [280.6-481.2] and 369.4 [299.6-433.6], respectively). The highest ASYR due to HPV infection was in South Africa (457.1 [453.3-462.6]). ASYRs for alcohol consumption and tobacco smoking were higher among men than women, whereas women had higher ASYRs for excess body weight and HPV infection. Our findings demonstrate the importance of cancer control efforts to reduce the burden of cancer death and YLLs due to modifiable cancer risk factors and promote the use of YLLs to summarise disease burden. Cancer Research UK.

Secondary risk reduction service acceptability amongst Irish breast cancer survivors and clinicians

Abstract Background Many patients (&amp;gt;75%) diagnosed with breast cancer in Ireland today will be cured and are at risk of dying from other cancers and non-communicable diseases. Breast cancer diagnosis provides a pivotal time point for education on modifiable risk factors and engagement with secondary risk reduction services. Our study set out to establish the level of awareness and acceptability of these areas, respectively. Methods A survey was developed for breast cancer survivors and oncology clinicians using previously validated questionnaires; the ‘Mitchelstown Cohort Survey’ and the ‘International Physical Activity Questionnaire'. IBM SPSS software (Version 28.0) was used for data analysis. Results Between September and December 2021, 322 patients and 29 clinicians attending the South Infirmary Victoria and Cork University Hospitals, completed the survey. Over 80% of patients and clinicians were aware of modifiable cancer risk factors. Only 1 in 5 clinicians had training in secondary risk reduction however 90% were willing to refer to services. Education had an impact on the likelihood of patient engagement with weight management, dietary, and exercise education (Pearson chi-squared test; p = 0.009, 0.039, 0.139 respectively). Patients who smoked, had increased alcohol intake, or gained weight since diagnosis were more likely to engage with services (p = &amp;lt;0.001, p = &amp;lt;0.001, p = 0.015 respectively). Patients who made changes to activity levels since diagnosis were more likely to engage with exercise education (p = 0.015). Conclusions This study identified that over 4 in 5 breast cancer survivors and oncology clinicians were aware of the importance of modifiable lifestyle risk factors. While 9 in 10 clinicians were willing to refer to secondary prevention services if available, the likelihood of patient engagement was associated with their at-risk behaviours and education level. Our study highlights the challenges of implementing health promotion programs in this cohort. Key messages • High level of intended engagement with secondary risk reduction services amongst breast cancer survivors and oncology clinicians. • Likelihood of patient engagement was associated with their at-risk behaviours and education level.

Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility.

5,10-methylenetetrahydrofolate reductase (MTHFR) mutations play a significant role in various types of cancers, serving as crucial regulators of folate levels in this process. Several studies have examined the effects of smoking and drinking on MTHFR-related cancers, yielding inconsistent results. Therefore, the objective of this study was to evaluate the magnitude of the effects of gene-smoking or gene-drinking interactions on cancer development. We conducted a comprehensive literature search in PubMed, Web of Science, CNKI, and Wan Fang databases up until May 10th, 2022, to identify relevant articles that met our inclusion criteria. The extracted data from these studies were used to calculate the overall odds ratio (OR) and corresponding 95% confidence interval (95% CI) using either a fixed-effect or random-effect model in Stata version 11.2. Stratified analyses were performed based on ethnicity, control group origin, and cancer classification to assess the risk of cancers associated with gene-smoking or gene-drinking interactions. Sensitivity analyses were conducted to investigate potential sources of heterogeneity, and publication bias was assessed using the Begg's test and Egger's test. Additionally, regression analysis was employed to explore the influence of relevant variables on heterogeneity. To evaluate the statistical correlations, analytical methods such as the false-positive report probability and the Bayesian false discovery probability were applied to assess the reliability of the findings. In our meta-analysis, a total of 47 articles were included, comprising 13,701 cases and 21,995 controls for the C677T polymorphism and 5,149 cases and 8,450 controls for the A1298C polymorphism. The results indicated a significant association between C677T polymorphism and cancer risks when combined with smoking (CT + TT vs CC, OR [95% CI] = 1.225 [1.009-1.487], p = 0.041). Stratified analysis further revealed a significant increase in liver cancer risk for individuals with the C677T when combined with smoking (liver cancer: CT + TT vs CC, OR [95% CI] = 1.564 [1.014-2.413], p = 0.043), particularly among Asian smokers (CT + TT vs CC, OR [95% CI] = 1.292 [1.007-1.658], p = 0.044). Regarding the A1298C polymorphism, an elevated risk of cancer was observed in mixed populations alone (CC + AC vs AA, OR [95% CI] = 1.609 [1.087-2.381], p = 0.018), as well as when combined with smoking (CC + AC vs AA, OR [95% CI] = 1.531 [1.127-2.080], p = 0.006). In non-drinkers, C677T polymorphism was found to be associated with esophageal cancer risk (C677T: CT + TT vs CC, OR [95% CI] = 1.544 [1.011-2.359], p = 0.044) and colon cancer risk (CC + AC vs AA, OR [95% CI] = 1.877 [1.166-3.054], p = 0.010), but there was no clear link between this polymorphism and cancer risk among drinkers. The association between the C677T polymorphism and cancer risk among smokers was found to be significant, suggesting that the combination of tobacco and the C677T polymorphism may enhance the carcinogenic process, particularly in liver cancer. However, no similar relationship was observed for the A1298C polymorphism. Interestingly, significantly increased cancer risk was observed in individuals with C677T genetic variants who were nondrinkers, but not among drinkers. These findings highlight the potential role of the C677T polymorphism in modifying cancer risk in specific contexts, such as smoking and alcohol consumption.

Impact of modifiable lifestyle risk factors for prostate cancer prevention: a review of the literature.

Although prostate cancer (PCa) is one of the most common cancers among men, the impact of modifiable risk and protective factors is still being debated. This review aims to qualitatively summarize the most recent studies related to potential healthy lifestyle factors affecting the development of PCa. The literature focusing on modifiable risk factors for prostate cancer was reviewed. Medline and Embase via the Ovid database were searched, and all relevant and inherent articles were analyzed. Non-eligible publications, such as review articles, editorials, comments, guidelines, or case reports, were excluded. This review confirms that there is strong evidence that being overweight or obese increases the risk of advanced prostate cancer (assessed by body mass index (BMI), waist circumference, and waist-hip ratio), particularly considering central adiposity and ethnicity as contributing factors. The possible contribution of smoking still seems not entirely clear, while alcohol seems to affect PCa prevention in patients taking 5α-reductase inhibitors (5-ARIs). Dietary fibers may have anti-inflammatory properties and improve insulin sensitivity by reducing IGF bioactivity. In particular, dietary fiber intake like insoluble and legume fibers may be inversely associated with prostate cancer risk. Also, hyperglycemia and hyperinsulinemia, with untreated diabetic fasting blood glucose levels, could be modifiable prostate cancer risk factors. In two studies, aspirin was associated with a lower risk of lethal PCa and overall mortality. Concerning the role of vitamins, despite conflicting and divergent results, serum retinol concentration seems to be associated with an increased risk of prostate cancer and high-grade prostate cancer. Some studies resulted in disagreement about the role of selenium and vitamin E. We found inconsistent and controversial findings about the association between vitamin D and prostate cancer risk. Far from being conclusive evidence, our findings confirm some strong evidence already found in the previous literature and highlight the need to clarify the role of some risk factors whose role is not yet completely known. This effort would facilitate the cultural and social change that may allow the shift from the treatment of prostate cancer when diagnosed to the real efforts needed for systematic prevention.

Novel Treatments for Obesity: Implications for Cancer Prevention and Treatment.

It is now established that obesity is related to a higher incidence of cancer during a lifespan. The effective treatment of obesity opens up new perspectives in the treatment of a relevant modifiable cancer risk factor. The present narrative review summarizes the correlations between weight loss in obesity and cancer. The current knowledge between obesity treatment and cancer was explored, highlighting the greatest potential for its use in the treatment of cancer in the clinical setting. Evidence for the effects of obesity therapy on proliferation, apoptosis, and response to chemotherapy is summarized. While more studies, including large, long-term clinical trials, are needed to adequately evaluate the relationship and durability between anti-obesity treatment and cancer, collaboration between oncologists and obesity treatment experts is increasingly important.