Risk Factor For Cancer Incidence Research Articles

Abstract 4123540: Cardiovascular Health and Cancer Incidence and Mortality: NHANES-III and -Continuous study

Background: Cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Limited evidence is available regarding the relationship between CVD, cardiovascular risk factors (CVRF), and cancer mortality; and how CVRF further modify that relationship. Methods: The first part included 438 and 2100 CVD patients aged 65+ from NHANES-III and Continuous (1999-2016) datasets, respectively. Competing risk models with subdistribution hazards ratio (aHR) were used to identify risk factors for cancer incidence. The second part included 44,591 adult individuals from NHANES-Continuous merged with Medicare and National Death Index mortality data until the end of 2018. We included individuals with no history of cancer at baseline. We used competing risk modeling to test the relationship between CVD at baseline and cancer mortality. We also conducted a comprehensive risk factor analysis. Results: In the first part (Figure), females in NHANES-III had lower cancer risk (aHR 0.39, P=0.001) compared to males. Poor physical activity was associated with increased cancer risk in both datasets (aHR 2.59 in NHANES-III, aHR 1.59 in Continuous). In NHANES-Continuous, age (aHR 1.07, P<0.001) and current smoking (aHR 2.55, P=0.001) showed a significant association with developing cancer. No other factors investigated showed significant associations. In the second analysis (Table), the included sample size represented 1,738,423,317 individuals (52% females, 67% non-Hispanic Whites, and 9% Hispanics). Competing risk modeling showed a significantly higher risk of cancer mortality in individuals with CVD (aHR 1.37, 95% CI 1.07-1.76, P=0.01) after adjusting for age, sex, and race/ethnicity. Notably, cancer mortality increased with aging (aHR 1.08, 95%CI 1.05-1.11, P<0.0001), current smoking status (aHR 6.78, 95%CI 3.43-13.42, P<0.0001), and obesity (aHR 2.32, 95%CI 1.13-4.79, P=0.02). Finally, a significant interaction (P=0.034) was found where those with CVD and obesity showed higher cancer mortality than those with normal BMI (aHR, 95%CI 1.03-2.91, P=0.04). Conclusions: Our study highlights the close relationship between cardiovascular health and cancer, including among CVD patients. Our findings suggest that physical activity and obesity may play a significant role in cancer incidence and mortality among the general population and CVD patients. These findings emphasize the need for more proactive approach in the management of shared risk factors for CVD and cancer.

Early-onset and later-onset cancer: trends, risk factors, and prevention in Northern China.

The characteristics of early-onset (onset age <50 years) and later-onset (onset age ≽ 50 years) cancers differ significantly. Identifying novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its burden. This study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset cancers. We conducted a prospective study by drawing data from the Kailuan Study. This study included 6,741 participants with cancer (624 with early-onset cancer and 6,117 with later-onset cancer) and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to 2019. The primary outcomes were cancer incidence rates, and associated risk factors for early- and later-onset cancer. Weighted Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early- and later-onset cancer by cancer type. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the population. Except for liver cancer, incidence rates for nearly all types of cancer increased during the study period. Smoking, alcohol consumption, lipid metabolism disorders, hypertension, diabetes mellitus, fatty liver, and inflammation were associated with a significantly increased risk of cancer at multiple sites, but risk factors for cancer incidence differed by site. Smoking, alcohol consumption, inflammation, and hypertension were the major contributors to preventable cancer. The incidence of several different types of cancer, including early-onset cancer, is increasing in northeastern China. Differences in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

Joint association of biological aging and lifestyle with risks of cancer incidence and mortality: A cohort study in the UK Biobank

BackgroundAging is a risk factor for cancer incidence and mortality. Biological aging can reflect the aging degree of the body better than chronological age and can be aggravated by unhealthy lifestyle factors. We aimed to assess the joint effect of biological aging and lifestyle with risks of cancer incidence and mortality. MethodsThis study included a total of 281,889 participants aged 37 to 73 from the UK Biobank database. Biological age was derived from chronological age and 9 clinical blood indicators, and lifestyle score was constructed by body mass index, smoking status, alcohol consumption, physical activity, and diet. Multivariate Cox hazard proportional regression model was used to analyze the independent and joint association of biological aging and lifestyle with risks of cancer incidence and mortality, respectively. ResultsOver a median follow-up period of 12.3 years, we found that older biological age was associated with increased risks of overall cancer, digestive system cancers, lung, breast and renal cancers incidence and mortality (HRs: 1.12–2.25). In the joint analysis of biological aging and lifestyle with risks of cancer incidence and mortality, compared with unhealthy lifestyle and younger biological age, individuals with healthy lifestyle and older biological age had decreased risks of incidence (8% ∼ 60%) and mortality (20% ∼ 63%) for overall, esophageal, colorectal, pancreatic and lung cancers. ConclusionsBiological aging may be an important risk factor for cancer morbidity and mortality. A healthier lifestyle is more likely to mitigate the adverse effects of biological aging on overall cancer and some site-specific cancers.

IBC-Oxford University2023_BJSOral_11Video Presentation: Laparoscopic Total Gastrectomy after Single Anastomosis Sleeve Jejunal Bypass

Abstract Introduction Amongst today's bariatric surgery procedures is the single anastomosis jejunal bypass operation (SASJ), which was first introduced by Professors Abdolreza Pazouki and Mohammad Kermansaravi. Single anastomosis sleeve ileal bypass (SASI) is a combined bariatric metabolic technique, in which few studies have shown its outcomes efficacy. However, this technique has a high risk of malnutrition due to long biliopancreatic limb. Single anastomosis sleeve jejunal bypass (SASJ) has a shorter limb. Therefore, it seems to have a lower risk of nutrient deficiency. Furthermore, this technique is relatively new, and little is known about the efficacy and safety of SASJ. Obesity is a significant risk factor for cancer incidence and mortality. The number of patients with obesity who undergo bariatric surgery is increasing; however, the impact of such a procedure in affecting the risk of cancer is not completely understood yet. The association between obesity and malignancies has been identified epidemiologically. Meanwhile, the increasing global number of bariatric surgeries is reported annually; bariatric surgery’s effect on different types of cancers is not well understood. Unfortunately, nonspecific presentations and difficulties regarding investigations make diagnosis challenging. Methods In this video case report, the patient was 62-year-old female with an initial BMI 44.2 kg/m2, weight: 116 kg and Height: 162 cm at the time of SASJ 6 years ago, upper gastrointestinal Endoscopy from 2017 before SASJ operation showed reflux esophagitis grade A and erosive erythematous hyperaemic mucosa gastritis. She underwent primary laparoscopic SASJ bypass in 2017. However, she had adequate weight loss for 5 years post-operative, and then she had excessive weight loss during past year. According to the patient history she suffers heart burn, anorexia, nausea and vomiting since1 year back, usually vomiting is present 2 hours postprandial with dark and black coloured content, and now her BMI is 21kg/m2. She had an upper GI endoscopy during past year, the last endoscopy report in 2023 commented on active and focally ulcerative mucosa with some atypical cells with signet ring pattern and chronic inflammatory responses, and biopsy showed adenocarcinoma of the stomach. Thorax, abdomen and pelvic CT scans were normal with no pathology is seen in upper GI contrast study. Laboratory findings were normal. A Laparoscopic Roux-en Y oesophago-jejunal bypass with a 75cm biliopancreatic limb and 75cm alimentary limb were performed. The patient was under complete screening for all over the last 1 so surgery is performed in first after confirmation of histopathology report before chemoradiotherapy (CRT). Results The operative time was 210 min and blood loss were 150ml. There were no intraoperative or postoperative complications. The patient had an uneventful postoperative course and was discharged on postoperative day 8. Conclusion Laparoscopic total gastrectomy with dissection of all lymph node from gastric stations is performed prior to the chemoradiotherapy for reaching the purpose of early malignancy control.

Association Between Cardiorespiratory Fitness and Cancer Incidence and Cancer-Specific Mortality of Colon, Lung, and Prostate Cancer Among Swedish Men

Cardiorespiratory fitness (CRF) levels appear to be an important risk factor for cancer incidence and death. To examine CRF and prostate, colon, and lung cancer incidence and mortality in Swedish men, and to assess whether age moderated any associations between CRF and cancer. A prospective cohort study was conducted in a population of men who completed an occupational health profile assessment between October 1982 and December 2019 in Sweden. Data analysis was performed from June 22, 2022, to May 11, 2023. Cardiorespiratory fitness was assessed as maximal oxygen consumption, estimated using a submaximal cycle ergometer test. Data on prostate, colon, and lung cancer incidence and mortality were derived from national registers. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression. Data on 177 709 men (age range, 18-75 years; mean [SD] age, 42 [11] years; mean [SD] body mass index, 26 [3.8]) were analyzed. During a mean (SD) follow-up time of 9.6 (5.5) years, a total of 499 incident cases of colon, 283 of lung, and 1918 of prostate cancer occurred, as well as 152 deaths due to colon cancer, 207 due to lung cancer, and 141 deaths due to prostate cancer. Higher levels of CRF (maximal oxygen consumption as milliliters per minute per kilogram) were associated with a significantly lower risk of colon (HR, 0.98, 95% CI, 0.96-0.98) and lung cancer (HR, 0.98; 95% CI, 0.96-0.99) incidence, and a higher risk of prostate cancer incidence (HR, 1.01; 95% CI, 1.00-1.01). Higher CRF was associated with a lower risk of death due to colon (HR, 0.98; 95% CI, 0.96-1.00), lung (HR, 0.97; 95% CI, 0.95-0.99), and prostate (HR, 0.95; 95% CI, 0.93-0.97) cancer. After stratification into 4 groups and in fully adjusted models, the associations remained for moderate (>35-45 mL/min/kg), 0.72 (0.53-0.96) and high (>45 mL/min/kg), 0.63 (0.41-0.98) levels of CRF, compared with very low (<25 mL/min/kg) CRF for colon cancer incidence. For prostate cancer mortality, associations remained for low (HR, 0.67; 95% CI, 0.45-1.00), moderate (HR, 0.57; 95% CI, 0.34-0.97), and high (HR, 0.29; 95% CI, 0.10-0.86) CRF. For lung cancer mortality, only high CRF (HR, 0.41; 95% CI, 0.17-0.99) was significant. Age modified the associations for lung (HR, 0.99; 95% CI, 0.99-0.99) and prostate (HR, 1.00; 95% CI, 1.00-1.00; P < .001) cancer incidence, and for death due to lung cancer (HR, 0.99; 95% CI, 0.99-0.99; P = .04). In this cohort of Swedish men, moderate and high CRF were associated with a lower risk of colon cancer. Low, moderate, and high CRF were associated with lower risk of death due to prostate cancer, while only high CRF was associated with lower risk of death due to lung cancer. If evidence for causality is established, interventions to improve CRF in individuals with low CRF should be prioritized.

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

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

Does OSA Increase Risk for Cancer?: A Large Historical Sleep Clinic Cohort Study

The relationship between OSA and cancer is unclear. What is the association between OSA and cancer prevalence and incidence in a large Western Australian sleep clinic cohort (N= 20,289)? OSA severity was defined by apnea-hypopnea index (AHI) and nocturnal hypoxemia (duration and percentage at oxygen saturation< 90%) measured by in-laboratory polysomnogram. Measures of potential confounding included age, sex, BMI, smoking, socioeconomic status, and BP. Outcomes were determined from the Western Australian cancer and death registries. Analyses were confined within periods using consistent AHI scoring criteria: January 1, 1989, to July 31, 2002 (American Sleep Disorders Association [ASDA] criteria), and August 1, 2002, to June 30, 2013 (Chicago criteria). We examined associations of AHI and nocturnal hypoxemia with cancer prevalence using logistic regression and cancer incidence using Cox regression analyses. Cancer prevalence at baseline was 329 of 10,561 in the ASDA period and 633 of 9,728 in the Chicago period. Nocturnal hypoxemia but not AHI was independently associated with prevalent cancer following adjustment for participant age, sex, BMI, smoking, socioeconomic status, and BP. Of those without prevalent cancer, cancer was diagnosed in 1,950 of 10,232 (ASDA) and 623 of 9,095 (Chicago) participants over a median follow-up of 11.2 years. Compared with the reference category (no OSA, AHI< 5 events per hour), univariable models estimated higher hazard ratios for cancer incidence for mild (AHI 5-15 events per hour), moderate (AHI 15.1-30 events per hour), and severe (AHI > 30 events per hour) OSA. Multivariable analyses consistently revealed associations between age and, in some cases, sex, BMI, and smoking status, with cancer incidence. After adjusting for confounders, multivariable models showed no independent association between OSA severity and increased cancer incidence. Nocturnal hypoxemia is independently associated with prevalent cancer. OSA severity is associated with incident cancer, although this association seems secondary to other risk factors for cancer development. OSA is not an independent risk factor for cancer incidence.

Translational and transdisciplinary research in energy balance and cancer: past is prologue.

Obesity, defined as a body mass index ≥ 30 kg/m2, is associated with an increased incidence of 13 cancers and increased mortality of 14 cancers (1,2). Obesity is strongly linked to poor diet and physical inactivity, which are also independent risk factors for cancer incidence and mortality (3-5). Estimates suggest that by 2030 obesity will overtake tobacco as the most common preventable risk factor for the development of cancer. Today, approximately 40% of US adults have a body mass index > 30 kg/m2, with rates significantly higher in Black and Hispanic individuals, especially women (6). Rising rates of obesity and associated factors threaten to slow advances in cancer prevention and treatment, underscoring the critical need for research on the causal role of body composition, physical activity, and diet in cancer risk and outcomes. Substantial gaps exist in our understanding of the relationship between energy balance and cancer. Much of the evidence to date has focused on breast cancer, generated from individuals of middle-to-higher socioeconomic status with early-stage malignancies (4). Research is needed to understand the role of obesity in influencing risk and outcomes of understudied obesity-associated cancers and in racial and ethnic minorities, patients undergoing active treatment or who have metastatic disease, cancer survivors with low income and who live in rural settings, as well as younger and geriatric populations. Mechanistic research is needed to elucidate associations of energy balance with the microbiome, epigenetics, immune function, immunotherapy, and cancer. Research is also needed on how to effectively implement and disseminate lifestyle interventions in oncology practice. In addition, research must focus on how to develop and assess successful multi-level intervention strategies at the individual and community levels. The National Cancer Institute Fiscal Year 2022 Annual Plan and Budget proposal featured obesity and cancer as a scientific topic and highlighted the importance of investing in training the next generation of cancer researchers (7). Transdisciplinary training is needed to prepare researchers to innovatively address these complex topics.

Sarcopenia as an Independent Risk Factor for Specific Cancers: A Propensity Score-Matched Asian Population-Based Cohort Study.

Simple SummaryWhether preexisting sarcopenia independently leads to cancer incidence remains unclear. Our study investigated the effect of sarcopenia on cancer incidence. We designed a propensity score–matched population-based cohort study to demonstrate that sarcopenia onset before cancer might be associated with cancer risk. We determined the significant adjusted incidence rate ratios (IRRs) of cancer risk on lung, colorectal, breast, head and neck, pancreas, gastric, esophageal, and ovarian cancers and hepatocellular carcinoma in patients with or without diagnosed sarcopenia before cancer.Purpose: Whether preexisting sarcopenia is an independent risk factor for cancer incidence remains unclear. Therefore, we performed this propensity score (PS)-matched (PSM) population-based cohort study to compare the incidence rate ratios (IRRs) of specific cancers between patients with and without sarcopenia. Patients and Methods: The patients were categorized into two groups according to the presence or absence of sarcopenia, matched at a 4:1 ratio. Results: PS matching yielded a final cohort of 77,608 patients (15,527 in the sarcopenia and 62,081 nonsarcopenia groups) eligible for further analysis. In our multivariate Cox regression analysis, compared with the nonsarcopenia group, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for cancer risk in the sarcopenia group was 1.277 (1.10 to 1.36; p < 0.001). Furthermore, the adjusted IRRs (95% CIs) for sarcopenia patients were pancreatic cancer 3.77 (1.79 to 4.01), esophageal cancer 3.38 (1.87 to 4.11), lung cancer 2.66 (1.15 to 2.90), gastric cancer 2.25 (1.54 to 3.23), head and neck cancer 2.15 (1.44 to 2.53), colorectal cancer 2.04 (1.77 to 2.30), hepatocellular carcinoma 1.84 (1.30 to 2.36), breast cancer 1.56 (1.12 to 1.95), and ovarian cancer 1.43 (1.10 to 2.29), respectively. Conclusions: Sarcopenia might be a significant cancer risk factor for lung, colorectal, breast, head and neck, pancreas, gastric, esophageal, and ovarian cancer, as well as hepatocellular carcinoma.

U-shaped association between body mass index and health-related quality of life impairment in Korean cancer survivors: a nationwide representative cross-sectional survey.

Although obesity is an important risk factor for cancer incidence, the effect of body mass index (BMI) on health-related quality of life (HRQoL) after cancer treatment remains unknown. This population-based cross-sectional study assessed different levels of BMI as an important factor associated with impaired HRQoL in long-term cancer survivors. The study enrolled 1104 cancer survivors from the fourth to seventh Korea National Health and Nutrition Examination Surveys (KNHANES 2007-2018) who were alive at least 5years after their cancer diagnoses. The BMI was classified into four categories: < 20 (underweight), 20-22.9 (healthy weight), 23-24.9 (overweight), and ≥ 25kg/m2 (obese). Impaired HRQoL was defined as the lowest quartile of European Quality of Life 5-Dimensions (EQ-5D) questionnaire scores. Cancer survivors who were underweight or obese were more likely to report health problems on each dimension of the EQ-5D compared to the other BMI groups. In multivariate logistic regression analysis, the two extreme BMI categories were significantly associated with impaired HRQoL (BMI < 20kg/m2: odds ratio [OR] = 1.73, 95% confidence interval [CI] = 1.08-2.86; BMI ≥ 25kg/m2: OR = 2.14, 95% CI = 1.41-3.25; P trend = 0.049), especially in the gastrointestinal cancer group (P heterogeneity = 0.007). Moreover, the association between underweight/obese and impaired HRQoL showed a significant sex difference (P heterogeneity = 0.019). The results of this study suggest that deviations from normal BMI, such as being underweight or obese, are negatively associated with HRQoL in long-term cancer survivors; to some extent, this may depend on cancer type and sex. Reaching or maintaining a healthy weight should be emphasized for cancer survivors as a long-term goal even after cancer treatment.

Human Microbiota and Immunotherapy in Breast Cancer - A Review of Recent Developments.

Breast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Infectious agents are the third most important risk factor for cancer incidence after tobacco and obesity. Dysbiosis emerged as a key player that may influence cancer development, treatment, and prognosis through diverse biological processes. Metastatic BC has a highly variable clinical course, and more recently, immune checkpoint inhibitors (ICIs) have become an emerging therapy in BC. Even with standardised treatment protocols, patients do not respond similarly, reflecting each individual´s heterogeneity, unique BC features, and tumour microenvironment. However, there is insufficient data regarding predictive factors of response to available treatments for BC. The microbiota could be a crucial piece of the puzzle to anticipate better individual BC risk and prognosis, pharmacokinetics, pharmacodynamics, and clinical efficacy. In recent years, it has been shown that gut microbiota may modulate cancer treatments’ efficacy and adverse effects, and it is also apparent that both cancer itself and anticancer therapies interact with gut microbiota bidirectionally. Moreover, it has been proposed that certain gut microbes may protect the host against inappropriate inflammation and modulate the immune response. Future clinical research will determine if microbiota may be a prognostic and predictive factor of response to ICI and/or its side effects. Also, modulation of microbiota can be used to improve outcomes in BC patients. In this review, we discuss the potential implications of metabolomics and pharmacomicrobiomics that might impact BC immunotherapy treatment.

Obesity and Cancer: the Profile of a Population who Underwent Bariatric Surgery

Obesity is a significant risk factor for cancer incidence and mortality. The number of patients with obesity who undergo bariatric surgery is increasing; however, the impact of such a procedure in affecting the risk of cancer is not completely understood yet. We conducted a retrospective unicentric cohort study to characterize the occurrence of cancer in patients who underwent bariatric surgery from January 2010 to December 2018. For cases of cancer identified after bariatric surgery, we performed a cancer-free survival analysis over time. We also performed a cross-sectional analysis of demographic and clinical characteristics at the time of surgery and compared patients with or without a cancer diagnosis. Of the 2578 patients who underwent bariatric surgery, 117 patients (4.5%) were diagnosed with a cancer. Fifty-nine cases were diagnosed before surgery, and the remaining 58 cases occurred after the bariatric procedure. The prevalence of cancer was more accentuated in women (4.9%) than among men (2.7%). Thyroid and breast cancer were the most frequent before and after bariatric surgery, respectively. On average, patients with cancer diagnosis were older (49.0 vs 43.3 years, p<0.001) and with a lower level of education (7.4 vs 8.6 school years, p=0.002). Almost all the cases of cancer identified in this study were obesity-related cancers. Further prospective studies are needed to extend the current knowledge regarding the cancer risk profile of patients who undergo bariatric surgery.

Living alone as a risk factor for cancer incidence, case-fatality and all-cause mortality: A nationwide registry study

Lack of social contacts has been associated with an increased risk of cancer mortality, but it is not known whether living alone increases the risk of cancer incidence or case fatality. We examined the association between living alone with cancer incidence, case-fatality and all-cause mortality in eight most common cancers. All patients with their first cancer diagnosis in 2000–2017 were identified from the nationwide Finnish Cancer Registry. Information on living arrangements was derived from Statistics Finland. The incidence analyses were conducted using Poisson regression. The total Finnish population served as the population at risk. Fine-Gray model was used to estimate case-fatality and Cox proportional regression model all-cause mortality. In men, we found an association between history of living alone and excess lung cancer incidence but living alone seemed to be associated with lower incidence of prostate cancer and skin melanoma. In women, living alone was more consistently associated with higher incidence of all studied cancers. Cancer patients living alone had an 11%–80% statistically significantly increased case-fatality and all-cause mortality in all studied cancers in men and in breast, colorectal and lung cancer in women. Living alone is consistently associated with increased cancer incidence risk in women but only in some cancers in men. Both men and women living alone had an increased risk of all-cause mortality after cancer diagnosis.

Associations of six adiposity-related markers with incidence and mortality from 24 cancers\u2014findings from the UK Biobank prospective cohort study

BackgroundAdiposity is a strong risk factor for cancer incidence and mortality. However, most of the evidence available has focused on body mass index (BMI) as a marker of adiposity. There is limited evidence on relationships of cancer with other adiposity markers, and if these associations are linear or not. The aim of this study was to investigate the associations of six adiposity markers with incidence and mortality from 24 cancers by accounting for potential non-linear associations.MethodsA total of 437,393 participants (53.8% women; mean age 56.3 years) from the UK Biobank prospective cohort study were included in this study. The median follow-up was 8.8 years (interquartile range 7.9 to 9.6) for mortality and 9.3 years (IQR 8.6 to 9.9) for cancer incidence. Adiposity-related exposures were BMI, body fat percentage, waist-hip ratio, waist-height ratio, and waist and hip circumference. Incidence and mortality of 24 cancers sites were the outcomes. Cox proportional hazard models were used with each of the exposure variables fitted separately on penalised cubic splines.ResultsDuring follow-up, 47,882 individuals developed cancer and 11,265 died due to cancer during the follow-up period. All adiposity markers had similar associations with overall cancer incidence. BMI was associated with a higher incidence of 10 cancers (stomach cardia (hazard ratio per 1 SD increment 1.35, (95% CI 1.23; 1.47)), gallbladder (1.33 (1.12; 1.58)), liver (1.27 (1.19; 1.36)), kidney (1.26 (1.20; 1.33)), pancreas (1.12 (1.06; 1.19)), bladder (1.09 (1.04; 1.14)), colorectal (1.10 (1.06; 1.13)), endometrial (1.73 (1.65; 1.82)), uterine (1.68 (1.60; 1.75)), and breast cancer (1.08 (1.05; 1.11))) and overall cancer (1.03 (1.02; 1.04)). All these associations were linear except for breast cancer in postmenopausal women. Similar results were observed when other markers of central and overall adiposity were used. For mortality, nine cancer sites were linearly associated with BMI and eight with waist circumference and body fat percentage.ConclusionAdiposity, regardless of the marker used, was associated with an increased risk in 10 cancer sites.

All-cancer incidence in Tehranian adults: more than a decade of follow-up—results from the Tehran Lipid and Glucose Study

ObjectivesTo investigate the incidence rates for different malignancies and assess the risk factors for all-cancer incidence in Tehran. Study designCohort study. MethodsThis study consists of 8599 participants aged ≥ 30 years who were free of cancer (3935 men). Cancer diagnosis was based on pathology reports. Sex-stratified crude incidence rates and age-standardized incidence rates (ASRs) using Segi's method were calculated for all-cancers. Multivariate Poisson regression models were used to evaluate associations of potential risk factors, including sex, age, obesity status (body mass index [BMI]: 25–30 kg/m2 as reference), education, smoking status, and diabetes mellitus with the incidence of cancers among the population. Incidence rate ratios (IRRs) with 95% confidence interval (CI) were also reported. ResultsDuring a median follow-up of 13.9 years, there were 130 and 129 incident cancers for men and women, respectively; the corresponding ASRs were 356.1 and 243.6 per 100,000 person-years, respectively. The three most incident cancers among men were gastrointestinal (GI) (ASR = 127.5), hematopoietic (ASR = 99.5), and reproductive system malignancies (ASR = 46.3). The most common incident cancers in women were breast cancer (ASR = 92.1), GI (ASR = 65.4), and reproductive system malignancies (ASR = 16.8). Among risk factors for cancer incidence, age (IRR [95% CI]: 1.05 [1.03–1.06]) and having a BMI < 25 kg/m2 (IRR [95% CI]: 1.38 [1.01–1.90]) had a statistically significant association with incident cancer. ConclusionsThe high rates of cancers in Tehran during more than a decade of follow-up calls for a need to define risk factors as well as to implement programs for early screening.

Care-paradigm shift promoting smoking cessation treatment among cancer center patients via a low-burden strategy, Electronic Health Record-Enabled Evidence-Based Smoking Cessation Treatment.

Tobacco smoking is an important risk factor for cancer incidence, an effect modifier for cancer treatment, and a negative prognostic factor for disease outcomes. Inadequate implementation of evidence-based smoking cessation treatment in cancer centers, a consequence of numerous patient-, provider-, and system-level barriers, contributes to tobacco-related morbidity and mortality. This study provides data for a paradigm shift from a frequently used specialist referral model to a point-of-care treatment model for tobacco use assessment and cessation treatment for outpatients at a large cancer center. The point-of-care model is enabled by a low-burden strategy, the Electronic Health Record-Enabled Evidence-Based Smoking Cessation Treatment program, which was implemented in the cancer center clinics on June 2, 2018. Five-month pre- and post-implementation data from the electronic health record (EHR) were analyzed. The percentage of cancer patients assessed for tobacco use significantly increased from 48% to 90% (z = 126.57, p < .001), the percentage of smokers referred for cessation counseling increased from 0.72% to 1.91% (z = 3.81, p < .001), and the percentage of smokers with cessation medication significantly increased from 3% to 17% (z = 17.20, p < .001). EHR functionalities may significantly address barriers to point-of-care treatment delivery, improving its consistent implementation and thereby increasing access to and quality of smoking cessation care for cancer center patients.

Frontline Science: High fat diet and leptin promote tumor progression by inducing myeloid-derived suppressor cells.

Obesity is a risk factor for cancer incidence and cancer mortality. The association of obesity and cancer is attributed to multiple factors, but the tightest linkage is with the chronic, low-grade inflammation that accompanies obesity. Myeloid-derived suppressor cells (MDSC) are known facilitators of cancer progression that act by suppressing the activation and function of tumor-reactive T cells. Because MDSC quantity and function are driven by chronic inflammation, we hypothesized that MDSC may accumulate in obese individuals and facilitate tumor growth by suppressing antitumor immunity. To test this hypothesis, tumor-bearing mice on a high fat or low fat diet (HFD or LFD) were assessed for tumor progression and the metabolic dysfunction associated with obesity. HFD enhanced the accumulation of MDSC, and the resulting MDSC had both beneficial and detrimental effects. HFD-induced MDSC protected mice against diet-induced metabolic dysfunction and reduced HFD-associated inflammation, but also increased the accumulation of fat, enhanced tumor progression, and spontaneous metastasis and reduced survival time. HFD-induced MDSC facilitated tumor growth by limiting the activation of tumor-reactive CD8+ T cells. Leptin, an adipokine that regulates appetite satiety and is overexpressed in obesity, undergoes crosstalk with MDSC in which leptin drives the accumulation of MDSC while MDSC down-regulate the production of leptin. Collectively, these studies demonstrate that although MDSC protect against some metabolic dysfunction associated with HFD they enhance tumor growth in HFD mice and that leptin is a key regulator linking HFD, chronic inflammation, immune suppression, and tumor progression.

The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance.

Growing evidence has raised the important roles of adipocytes as an active player in the tumor microenvironment. In many tumors adipocytes are in close contact with cancer cells. They secrete various factors that can mediate local and systemic effects. The adipocyte-cancer cell crosstalk leads to phenotypical and functional changes of both cell types, which can further enhance tumor progression. Moreover, obesity, which is associated with an increase in adipose mass and an alteration of adipose tissue, has been established as a risk factor for cancer incidence and cancer-related mortality. In this review, we summarize the mechanisms of the adipocyte-cancer cell crosstalk in both obese and lean conditions as well as its impact on cancer cell growth, local invasion, metastatic spread and resistance to treatments. Better characterization of cancer-associated adipocytes and the key molecular events in the adipocyte-cancer cell crosstalk will provide insights into tumor biology and suggest efficient therapeutic opportunities.

Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis.

Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer. Little is known regarding the impact of MG-mediated carbonyl stress on tumor progression. Breast tumors with MG stress presented with high nuclear YAP, a key transcriptional co-activator regulating tumor growth and invasion. Elevated MG levels resulted in sustained YAP nuclear localization/activity that could be reverted using Carnosine, a scavenger for MG. MG treatment affected Hsp90 chaperone activity and decreased its binding to LATS1, a key kinase of the Hippo pathway. Cancer cells with high MG stress showed enhanced growth and metastatic potential in vivo. These findings reinforce the cumulative evidence pointing to hyperglycemia as a risk factor for cancer incidence and bring renewed interest in MG scavengers for cancer treatment.

Intrinsic Versus Extrinsic Cancer Risk Factors and Aging

Two recent stimulating publications have examined the causes of cancer, comparing 'bad luck' versus environment as main risk factors for cancer incidence. However, bringing aging into the picture might question the entire debate.