Safety of Immunosuppression in a Prospective Cohort of Inflammatory Bowel Disease Patients With a HIstoRy of CancEr: SAPPHIRE Registry.

BACKGROUND & AIMS: In patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have suggested that exposure to immunosuppressive agents does not increase the risk of incident (recurrent or new) cancer compared with unexposed patients. SAPPHIRE is a prospective registry aimed at addressing this issue. METHODS: Since 2016, patients with IBD and confirmed index cancer before enrollment were followed up annually. Patients receiving chemotherapy or radiation at enrollment, or recurrent cancer within 5 years, were excluded. The primary outcome was development of incident cancer related to exposure to immunosuppressive medications. RESULTS: Among 305 patients (47% male, 88% white), the median age at IBD diagnosis and cancer were 32 and 52 years, respectively. Index cancers were solid organ (46%), dermatologic (32%), gastrointestinal (13%), and hematologic (9%). During a median follow-up period of 4.8 years, 210 patients (69%) were exposed to immunosuppressive therapy and 46 patients (15%) developed incident cancers (25 new, 21 recurrent). In unadjusted analysis, the crude rate of incident cancer in unexposed patients was 2.58 per 100 person-years vs 4.78 per 100 person-years (relative risk, 1.85; 95% CI, 0.92-3.73) for immunosuppression-exposed patients. In a proportional hazards model adjusting for sex, smoking history, age and stage at index malignancy, and nonmelanoma skin cancer, no significant association was found between receipt of immunosuppression and incident cancer (adjusted hazard ratio, 1.41; 95% CI, 0.69-2.90), or with any major drug class. CONCLUSIONS: In this interim analysis of patients with IBD and a history of cancer, despite numerically increased adjusted hazard ratios, we did not find a statistically significant association between subsequent exposure to immunosuppressive therapies and development of incident cancers.

Ascertainment of Incident Cancer by US Population-Based Cancer Registries Versus Self-Reports and Death Certificates in a Nationwide Cohort Study, the US Radiologic Technologists Study.

Follow-up of US cohort members for incident cancer is time-consuming, is costly, and often results in underascertainment when the traditional methods of self-reporting and/or medical record validation are used. We conducted one of the first large-scale investigations to assess the feasibility, methods, and benefits of linking participants in the US Radiologic Technologists (USRT) Study (n = 146,022) with the majority of US state or regional cancer registries. Follow-up of this cohort has relied primarily on questionnaires (mailed approximately every 10 years) and linkage with the National Death Index. We compared the level of agreement and completeness of questionnaire/death-certificate-based information with that of registry-based (43 registries) incident cancer follow-up in the USRT cohort. Using registry-identified first primary cancers from 1999-2012 as the gold standard, the overall sensitivity was 46.5% for self-reports only and 63.0% for both self-reports and death certificates. Among the 37.0% false-negative reports, 27.8% were due to dropout, while 9.2% were due to misreporting. The USRT cancer reporting patterns differed by cancer type. Our study indicates that linkage to state cancer registries would greatly improve completeness and accuracy of cancer follow-up in comparison with questionnaire self-reporting. These findings support ongoing development of a national US virtual pooled registry with which to streamline cohort linkages.

The "unnatural" history of colorectal cancer in Lynch syndrome: Lessons from colonoscopy surveillance.

Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS-associated CRC. Alongside with hypotheses addressing colonoscopy quality and pace of progression from adenoma to cancer, we discuss the role of alternative precursors and immune system in LS-associated CRC. We also identify gaps in current knowledge and make suggestions for future studies aiming at improved CRC prevention for LS individuals.

Plasma Magnesium Concentrations and Risk of Incident Cancer in Adults with Hypertension: A Nested Case-Control Study.

OBJECTIVE: The association between plasma magnesium and risk of incident cancer remains inconclusive in previous studies. We aimed to investigate the prospective relationship of baseline plasma magnesium concentrations with the risk of incident cancer and to examine possible effect modifiers. METHODS: A nested case-control study with 228 incident cancer cases and 228 matched controls was conducted using data from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, controlled trial, conducted from May 2008 to August 2013. Study outcomes included incident cancer and its subtypes. RESULTS: When plasma magnesium concentrations were assessed as quartiles, a significantly higher incident risk of total cancer was found in participants in quartile 1 (<0.76 mmol/L; odds ratio [OR] = 2.70; 95% CI: 1.33-5.49) and quartile 4 (≥0.89 mmol/L; OR = 2.05; 95% CI: 1.12-3.76), compared with those in quartile 3 (0.83 to <0.89 mmol/L). In cancer site-specific analyses, similar trends were found for gastrointestinal cancer, esophageal cancer, gastric cancer, breast cancer, lung cancer, and other cancers. Furthermore, none of the variables, including age, sex, current smoking status, current alcohol intake, BMI, systolic blood pressure, and total cholesterol levels at baseline significantly modified the association between plasma magnesium and cancer risk. CONCLUSIONS: Both low and high plasma magnesium concentrations were significantly associated with an increased incident risk of cancer, compared with the reference concentrations of 0.83 to <0.89 mmol/L among hypertensive adults.

The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: a cohort study.

AIMS: Low-grade inflammation, measured by elevated plasma concentrations of high-sensitive C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that low-grade inflammation is also related to a higher risk of cancer. The present prospective cohort study evaluates the relation between low-grade systemic inflammation and risk of cancer in patients with stable CVD. METHODS AND RESULTS: In total, 7178 patients with stable CVD and plasma CRP levels ≤10 mg/L were included. Data were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident CVD and cancer. After a median follow-up time of 8.3 years (interquartile range 4.6-12.3) 1072 incident cancer diagnoses were observed. C-reactive protein concentration was related to total cancer [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.10-1.65] comparing last quintile to first quintile of CRP. Especially lung cancer, independent of histopathological subtype, was related to CRP (HR 3.39; 95% CI 2.02-5.69 comparing last to first quintile of CRP). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of anatomical location. Sensitivity analyses after excluding patients with a cancer diagnosis within 1, 2, and 5 years of follow-up showed similar results. No effect modification was observed by smoking status or time since smoking cessation (P-values for interaction > 0.05). CONCLUSION: Chronic systemic low-grade inflammation, measured by CRP levels ≤10 mg/L, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD. The relation between inflammation and incident cancer is seen in former and current smokers and is uncertain in never smokers.

Association between long-term low-intensity cigarette smoking and incidence of smoking-related cancer in the national institutes of health-AARP cohort.

An increasing proportion of US smokers smoke ≤10 cigarettes per day (CPD) or do not smoke every day, yet the health effects of low-intensity smoking are poorly understood. We identified lifelong smokers of <1 or 1-10 CPD and evaluated risk of incident cancer among 238,525 cancer-free adults, aged 59-82, in the NIH-AARP Diet and Health Study. A questionnaire administered in 2004-2005 assessed CPD during nine age-periods (<15 to ≥70). We estimated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable-adjusted Cox proportional hazards regression with age as the underlying time metric. Of the 18,233 current smokers, (7.6%), 137 and 1,243 reported consistently smoking <1 CPD and 1-10 CPD, respectively. Relative to never smokers, current smokers who reported consistently smoking 1-10 CPD over their lifetime were 2.34 (95% CI = 1.86-2.93) times more likely to develop smoking-related cancer. Current lifetime smokers of <1 CPD were 1.89 (95% CI = 0.90-3.96) times more likely to develop tobacco-related cancer, although the association did not reach statistical significance. Associations were observed for lifelong smoking of ≤10 CPD with lung cancer (HR = 9.65, 95% CI = 6.93-13.43); bladder cancer (HR = 2.22, 95% CI = 1.22-4.05); and pancreatic cancer (HR = 2.03, 95%CI: 1.05-3.95). Among lifelong ≤10 CPD smokers, former smokers had lower risks of smoking-related cancer with longer time since cessation and longer smoking duration. Lifelong <1 and 1-10 CPD smokers are at increased risk of incident cancer relative to never smokers and would benefit from cessation, providing further evidence that even low-levels of cigarette smoking cause cancer.

Spectrum of cancer risk among Taiwanese with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are liable to develop significant comorbidities, including lung cancer. Whether they are at a higher risk for cancer of other types remains debatable, especially for Asians. We studied the risk of incident cancer in COPD patients using a nationwide representative database, the Taiwan National Health Insurance Research Database. METHODS: From 1995 to 2008, 50,875 COPD patients who were free of antecedent malignancy were identified and followed up to development of malignancy, death or end of 2008, whichever came first. The risk of cancer was determined with the standardized incidence ratio (SIR), which is based on comparison to the national cancer incidence among the general population. RESULTS: During a median follow-up period of 5.61 years, 3623 (7.02 %) patients developed cancer and the SIR was 1.2 [95 % confidence interval (CI) 1.16-1.24, p < 0.001]. The risk remained higher at <1, 1-5, and even ≥5 years after the diagnosis of COPD (SIR 1.83, 1.07, and 1.11, respectively). Furthermore, the risk was significantly higher for some specific types of cancer, including head and neck cancer (SIR 1.23, 95 % CI 1.08-1.39, p = 0.002), esophageal cancer (SIR 1.35, 95 % CI 1.08-1.67, p = 0.010), lung and mediastinal cancer (SIR 1.86, 95 % CI 1.74-1.99, p < 0.001), breast cancer (SIR 1.19, 95 % CI 1.01-1.4, p = 0.041), prostate cancer (SIR 1.20, 95 % CI 1.06-1.35, p < 0.001), cancer of the central nervous system (SIR 1.58, 95 % CI 1.05-2.28, p = 0.030), lymphoma (SIR 1.53, 95 % CI 1.22-1.90, p < 0.001), and multiple myeloma (SIR 1.95, 95 % CI 1.31-2.80, p = 0.001). CONCLUSION: COPD patients had increased risk for incident cancers, including lung cancer and several extrapulmonary cancers.

Cardiac surgery and long-term risk for incident cancer: A nationwide population-based study.

OBJECTIVE: Previous studies indicate an increased long-term risk for incident cancer and cancer-specific mortality in patients undergoing cardiac surgery. We compared the risk for incident cancer and cancer-specific mortality between patients and matched control subjects from the general population. METHODS: All patients (n=127,119) undergoing first-time coronary artery and/or heart valve surgery in Sweden during 1997-2020 were included in a population-based observational cohort study based on individual data from the SWEDEHEART registry and four other mandatory national registries. The patients were compared with an age-, sex-, and place of residence-matched control population (n=415,287) using multivariable Cox proportional hazards regression models adjusted for baseline characteristics, co-morbidities, and socioeconomic factors. A propensity score-matched analysis with 81,522 well-balanced pairs was also performed. RESULTS: Median follow-up was 9.2 (range 0-24) years. A total of 31,361/127,119 (24.7%) of the patients and 102,959/415,287 (24.8%) control subjects developed cancer during follow-up. The crude event rates were 2.75 and 2.83 per 100 person-years, respectively. The adjusted risk for cancer and cancer-specific mortality was lower in patients (adjusted hazard ratios 0.86 (95% confidence interval (CI) 0.85-0.88) and 0.64 (95% CI 0.62-0.65), respectively). The propensity score-matched analysis showed similar results (hazard ratios 0.88 (95% CI 0.86-0.90) and 0.65 (95% CI 0.63 to 0.68), respectively). The results were consistent in subgroups based on sex, age, and comorbidities. CONCLUSIONS: Patients that underwent cardiac surgery have lower risk for cancer and cancer-specific mortality than matched control subjects.

The relationship between the morningness-eveningness questionnaire and incident cancer: A historical clinical cohort study.

OBJECTIVE: We conducted a retrospective cohort study to explore the relationship between chronotype measured by the total Morningness-Eveningness Questionnaire (MEQ) score and incident cancer. METHODS: We used clinical and provincial health administrative data on consecutive adults who underwent a Level 1 Polysomnography (PSG) and completed the MEQ between 2010 and 2015 in an academic hospital (Ontario, Canada) and were cancer-free at baseline. Cancer status was derived from the Ontario Cancer Registry. Individuals were followed until death or March 31, 2020. We used multivariable Cox cause-specific regressions to address the research objective. RESULTS: Of 3,004 individuals, 1,781 were analyzed: a median age of 54 years (IQR: 40-64) and 838 (47.1%) men. The median total MEQ score was 63 (IQR: 55-69); 61 (3.4%) were classified as evening (≤41), 536 (30.1%) as intermediate (42-58), and 1,184 (66.5%) as morning chronotypes (≥59). Over a median of 7 years (IQR: 5-8), 120 (6.7%) developed cancer. A U-shape relationship was found between the total MEQ score and an increased hazard of incident cancer, controlling for PSG measures of sleep apnea severity and sleep architecture, demographics, and comorbidities. Compared to the median of 63.0, a total MEQ score greater or less than the median was associated with an increased hazard of incident cancer, with the largest effect for those with a total score ≥76 (e.g., HR of a MEQ total score of 78 vs. 63: 2.01, 95% CI: 1.09-3.71). CONCLUSION: The U-shaped curve may reflect deviations from a standard circadian tendency, which may stress biological systems and influence malignancy risk.

Heart failure during acute coronary syndrome and the long-term cancer risk: the ABC-9 Study on heart disease.

AIMS: A higher risk of cancer among patients with heart failure (HF) has been suggested in recent community-based studies. This study aimed to investigate the impact of HF during hospitalization with acute coronary syndrome (ACS) on the long-term cancer risk. METHODS AND RESULTS: The study included 572 patients admitted with ACS to three Italian hospitals, discharged cancer-free, and prospectively followed for 24 years or until death. All but three patients completed the follow-up, which represented 6440 person-years (mean age: 66 ± 12 years; 70% males). Baseline HF was diagnosed in 192 (34%) patients. A total of 129 (23%) patients developed cancer (103 without HF and 26 with HF), and 107 (19%) patients died due to it (81 without HF and 26 with HF). The incidence rates for cancer onset and cancer death were not different according to HF status. Cox regression analysis revealed no association between HF or left ventricular ejection fraction (LVEF) and cancer risk. In addition, no difference in cancer risk was observed among patients with HF with preserved ejection fraction, HF with mildly reduced ejection fraction, and HF with reduced ejection fraction. In competing risk regression analysis, the risk of cancer onset associated with HF was sub-hazard ratio (SHR) 0.47 [95% confidence interval (CI): 0.30-0.72; P = 0.001] and SHR 1.02 (95% CI: 1.01-1.04; P = 0.002) with LVEF. Results were the same in the adjusted model. Yet the fully adjusted model showed an attenuated association between cancer death and HF (SHR: 0.63; 95% CI: 0.37-1.05; P = 0.08) and LVEF (SHR: 1.02; 95% CI: 0.99-1.06; P = 0.08). Consistent results were obtained after using propensity score matching analysis that created 192 pairs. A negative interaction between age and HF and a positive interaction between age and LVEF for cancer risk have also been found. CONCLUSIONS: An inverse association between baseline HF and long-term cancer risk has been observed among the ABC Study on heart disease patients who were followed for 24 years after ACS.

Polysomnographic Assessment of Sleep Disturbances in Cancer Development: A Historical Multicenter Clinical Cohort Study.

BACKGROUND: Many cellular processes are controlled by sleep. Therefore, alterations in sleep might be expected to stress biological systems that could influence malignancy risk. RESEARCH QUESTION: What is the association between polysomnographic measures of sleep disturbances and incident cancer, and what is the validity of cluster analysis in identifying polysomnography phenotypes? STUDY DESIGN AND METHODS: We conducted a retrospective multicenter cohort study using linked clinical and provincial health administrative data on consecutive adults free of cancer at baseline with polysomnography data collected between 1994 and 2017 in four academic hospitals in Ontario, Canada. Cancer status was derived from registry records. Polysomnography phenotypes were identified by k-means cluster analysis. A combination of validation statistics and distinguishing polysomnographic features was used to select clusters. Cox cause-specific regressions were used to assess the relationship between identified clusters and incident cancer. RESULTS: Among 29,907 individuals, 2,514 (8.4%) received a diagnosis of cancer over a median of 8.0 years (interquartile range, 4.2-13.5 years). Five clusters were identified: mild (mildly abnormal polysomnography findings), poor sleep, severe OSA or sleep fragmentation, severe desaturations, and periodic limb movements of sleep (PLMS). The associations between cancer and all clusters compared with the mild cluster were significant while controlling for clinic and year of polysomnography. When additionally controlling for age and sex, the effect remained significant only for PLMS (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.06-1.50) and severe desaturations (aHR, 1.32; 95% CI, 1.04-1.66). Further controlling for confounders, the effect remained significant for PLMS, but was attenuated for severe desaturations. INTERPRETATION: In a large cohort, we confirmed the importance of polysomnographic phenotypes and highlighted the role that PLMS and oxygenation desaturation may play in cancer. Using this study's findings, we also developed an Excel (Microsoft) spreadsheet (polysomnography cluster classifier) that can be used to validate the identified clusters on new data or to identify which cluster a patient belongs to. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT03383354 and NCT03834792; URL: www. CLINICALTRIALS: gov.

The association of serum betaine concentrations with the risk of new-onset cancers: results from two independent nested case-control studies.

Evidence from epidemiologic studies on the association of circulating betaine levels with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective association of serum betaine concentrations with the risk of cancer. We performed two, nested, case-control studies utilizing data from the "H-type Hypertension Prevention and Control Public Service Project" (HHPCP) and the China Stroke Primary Prevention Trial (CSPPT), with 2782 participants (1391 cancer cases and 1391 matched controls) in the discovery cohort, and 228 participants (114 cancer cases and 114 matched controls) in the validation cohort. Odds ratios (OR) of the association between betaine and cancer were calculated using conditional logistic regression models. There was an association between serum betaine as a continuous variable and total cancer (OR = 1.03, 95%CI = 0.99-1.07, p = 0.097). Among cancer subtypes, a positive association was found between serum betaine and the risk of lung cancer, and an inverse association was found with other cancers. Interestingly, a U-shaped association was observed between serum betaine and digestive cancers, with a turning point of 5.01 mmol/L for betaine (betaine < 5.01 mmol/L, OR = 0.82, 95%CI = 0.59-1.14, p = 0.228; betaine ≥ 5.01 mmol/L, OR = 1.08, 95%CI = 1.01-1.17, p = 0.036). In the validation cohort, a significant association between serum betaine as a continuous variable and total cancer (OR = 1.48, 95%CI = 1.06-2.05, P = 0.020) was also found. High serum betaine was associated with increased risk of total cancer and lung cancer, and a U-shaped association was found with the risk of digestive cancers, with a turning point at about 5.01 mmol/L.

Serum cholesterol and the risk of developing hormonally driven cancers: A narrative review.

Although cholesterol has been hypothesized to promote cancer development through several potential pathways, its role in the risk of developing hormonally driven cancer is controversial. This literature review summarizes evidence from the highest quality studies to examine the consistency and strength of the relationship between serum cholesterol parameters and incidence of hormonally driven cancer. Articles were identified using EMBASE. Longitudinal observational studies published between January 2000 and December 2020 were considered for inclusion. The endpoint of interest was incident prostate, ovary, breast, endometrium, and uterine cancers. In total, 2732 reports were identified and screened; 41 studies were included in the review. No associations were found for ovarian cancer. Most endometrial cancer studies were null. The majority (76.9%) of studies reported no association between cholesterol and prostate cancer. Data on breast cancer were conflicting, associations limited, and effect sizes modest. Our results do not provide evidence for a clear association between cholesterol and different types of incident, hormonally driven reproductive cancers. Future studies should investigate the impact of lipid-lowering therapy.

Management of Inflammatory Bowel Disease in Patients with Current or Past Malignancy.

Immunomodulators, conventional immunosuppressants, and/or biologics are used more often, earlier, and longer than before in patients with inflammatory bowel disease (IBD). Along with this, the lifetime risk for cancer is estimated to be 33% in the general population in Europe. Thus, physicians face therapeutic choices in an increasing number of IBD patients with current or past malignancy. Few data are available so far for managing this IBD subpopulation and this clinical concern still remains a critical situation for four reasons: (i) risk of reactivation of dormant micrometastasis with immunomodulators is of major concern, (ii) there is a knowledge gap about the safety of the most recent molecules, (iii) current guidelines do not recommend the use of immunomodulators within 2-5 years after a diagnosis of cancer, (iv) patients with previous cancers are excluded from clinical trials. There is a lack of scientific evidence supporting the non-use of immunomodulators in IBD patients with previous cancer. Indeed, accumulative data suggest that the risk for recurrent and new cancer in patients with a history of cancer is not increased by thiopurines and anti-TNF agents. Most recently, cohort studies have found no differences in incident cancer rates in IBD patients with prior malignancy treated with vedolizumab or ustekinumab compared to those treated with anti-TNF agents. Therefore, decisions should be shared by the oncologist and the patient, considering the natural history of cancer, the time elapsed since cancer diagnosis, and IBD prognosis.

The Role of Colonoscopy in the Management of Individuals with Lynch Syndrome: A Narrative Review.

The history of Lynch syndrome changed definitively in 2000, when a study published in Gastroenterology demonstrated a significant reduction in mortality among individuals with Lynch syndrome who undergo regular endoscopic surveillance. As a consequence of this clinical evidence, all scientific societies developed guidelines, which highlighted the role of colonoscopy in the management of Lynch syndrome, especially for individuals at high risk of colorectal cancer. Over the years, these guidelines were modified and updated. Specialized networks were developed in order to standardize endoscopic surveillance programs and evaluate all the clinical data retrieved by the results of colonoscopies performed for both the screening and the surveillance of individuals with Lynch syndrome. Recent data show that the impact of colonoscopy (with polypectomy) on the prevention of colorectal cancer in individuals with Lynch syndrome is less significant than previously thought. This narrative review summarizes the current discussion, the hypotheses elaborated and the algorithms depicted for the management of individuals with Lynch Syndrome on the basis of the recent data published in the literature.

Effect of proprotein convertase subtilisin/kexin type 9 inhibition on cancer events: A pooled, post hoc, competing risk analysis of alirocumab clinical trials.

OBJECTIVE: Assess the risk of new and worsening cancer events among participants who received the lipid-lowering therapy alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor. DESIGN: Pooled post hoc analysis. SETTING: Six phase 3 or phase 4 placebo-controlled randomised trials with alirocumab. PARTICIPANTS: A total of 24,070 patients from the safety population with complete dosing data (alirocumab, n = 12,533; placebo, n = 11,537). INTERVENTION: Alirocumab 75 mg, alirocumab 150 mg, alirocumab 75 mg increasing to 150 mg if low-density lipoprotein cholesterol <50 mg/dL not achieved, or placebo, all every 2 weeks. All participants received background high-intensity or maximum-tolerated statin therapy. OUTCOMES AND MEASURES: The first new or worsening incident cancer events were assessed during the treatment-emergent adverse event period. Four outcomes were evaluated: any-neoplasm, malignant neoplasms, broad definition of hormone-sensitive cancers, and stricter definition of hormone-sensitive cancers. Sub-distribution hazard ratios and 95% confidence intervals (CIs) were estimated using a competing risk framework, with death as a competing risk. RESULTS: Considering both treatment arms in aggregate, 969 (4.03%), 779 (3.24%), 178 (0.74%) and 167 (0.69%) patients developed any neoplasm, malignant neoplasms, broad definition of hormone-sensitive cancer and strict definition of hormone-sensitive cancer events, respectively. There was no significant difference in the risk of having any neoplasm in the alirocumab versus the placebo group (sub-distribution hazards ratio [95% CI], 0.93 [0.82-1.1]; p = 0.28). A nominally lower risk of having any neoplasms with alirocumab was observed among subjects aged ≥64 years (sub-distribution hazards ratio 0.83; 95% CI, 0.70-0.99). CONCLUSIONS: Intensive low-density lipoprotein cholesterol lowering with a proprotein convertase subtilisin/kexin type 9 inhibitor combined with statin does not appear to increase the risk of new or worsening cancer events.

Multifactorial Diseases of the Heart, Kidneys, Lungs, and Liver and Incident Cancer: Epidemiology and Shared Mechanisms.

Within the aging population, the frequency of cancer is increasing dramatically. In addition, multiple genetic and environmental factors lead to common multifactorial diseases, including cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and metabolic-associated fatty liver disease. In recent years, there has been a growing awareness of the connection between cancer and multifactorial diseases, as well as how one can affect the other, resulting in a vicious cycle. Although the exact mechanistic explanations behind this remain to be fully explored, some progress has been made in uncovering the common pathologic mechanisms. In this review, we focus on the nature of the link between cancer and common multifactorial conditions, as well as specific shared mechanisms, some of which may represent either preventive or therapeutic targets. Rather than organ-specific interactions, we herein focus on the shared mechanisms among the multifactorial diseases, which may explain the increased cancer risk. More research on this subject will highlight the significance of developing new drugs that target multiple systems rather than just one disease.

Comparative Risk of Incident Cancer in Patients with Inflammatory Bowel Disease with Prior Non-digestive Malignancy According to Immunomodulator: a Multicentre Cohort Study.

INTRODUCTION: Knowledge about the cancer risk when initiating a biologic in inflammatory bowel disease [IBD] patients with prior malignancy remains scarce, especially for vedolizumab. Our aim was to evaluate the rate of incident cancer in a cohort of IBD patients with prior non-digestive malignancy, according to the subsequent treatment given. METHODS: A multicentre retrospective study included consecutive IBD patients with prior non-digestive malignancy. Inclusion date corresponded to the diagnosis of index malignancy. Patients were categorized into different cohorts according to the first treatment [none, conventional immunosuppressant, anti-TNF, or vedolizumab] to which they were exposed after inclusion and before incident cancer [recurrent or new cancer]. RESULTS: Among the 538 patients {58% female; mean (standard deviation [SD]) age inclusion: 52 [15] years} analyzed, the most frequent malignancy was breast cancer [25%]. The first immunomodulator given after inclusion was a conventional immunosuppressant in 27% of patients, anti-TNF in 21%, or vedolizumab in 9%. With a median (interquartile range [IQR]) follow-up duration of 55 [23-100] months, 100 incident cancers were observed. Crude cancer incidence rates per 1000 person-years were 47.0 for patients receiving no immunomodulator, 36.6 in the anti-TNF cohort, and 33.6 in the vedolizumab cohort [p = 0.23]. Incident-cancer free survival rates were not different between patients receiving anti-TNF and those receiving vedolizumab [p = 0.56]. After adjustment, incidence rates were not different between patients receiving no immunomodulator, anti-TNF, or vedolizumab. CONCLUSIONS: In this large multicentre cohort study, there was no difference of cancer incidence in those IBD patients with prior non-digestive malignancy, treated with vedolizumab or anti-TNF.

The Association of Serum L-Carnitine Concentrations with the Risk of Cancer in Chinese Adults with Hypertension.

BACKGROUND: The effect of serum L-carnitine (LC) concentrations on cancer risk remains unclear. This study aims to explore the association between serum LC and the risk of incident cancer. METHODS: This is a case-control study, including 574 patients with incident cancer and 574 controls matched in a 1:1 ratio by age, sex, and residence, nested within the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analysis was used to assess the association of serum LC and incident cancer risk. RESULTS: When LC was assessed as quartiles, compared with patients with low LC (Q1), patients in the highest quartile (Q4) had a 33% (OR = 0.67, 95% CI: 0.46 to 0.99), 52% (OR = 0.48, 95% CI: 0.23 to 0.99), and 39% (OR = 0.61, 95% CI: 0.38 to 0.99) decreased risk of overall, digestive system, and non-digestive system cancer in the adjusted models, respectively. In subgroup analyses, an inverse association of LC with cancer risk was observed in individuals who were overweight (obese), who never drink, who never smoke, and who were female. In the mediation analysis, serum trimethylamine-N-oxide (TMAO) concentrations did not mediate the reversed association of LC with cancer risk. CONCLUSIONS: This study showed that serum LC concentrations had a protective impact on overall, digestive system, and non-digestive system cancer risk.

Incident Colorectal Cancer in Inflammatory Bowel Disease.

Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed in our multicenter study, including a cohort of 56 IBD patients with incident CRC. The clinical and histopathological features of IBD patients and of CRC were recorded. Incident CRC in IBD occurred at a young age (≤40 years) in 25% of patients (median age 55.5 (22-76)). Mucinous signet-ring carcinoma was detected in 6 out of the 56 (10.7%) patients, including 4 with Ulcerative Colitis (UC) and 2 with Crohn's disease (CD). CRC was more frequently diagnosed by colonoscopy in UC (85.4% vs. 50%; p = 0.01) and by imaging in Crohn's Disease CD (5.8% vs. 31.8%; p = 0.02). At onset, CRC-related symptoms occurred in 29 (51.9%) IBD patients. The time interval from the diagnosis of IBD to CRC was shorter in UC and CD patients with >40 years (p = 0.002; p = 0.01). CRC-related death occurred in 10 (29.4%) UC and in 6 (27.2%) CD patients (p = 0.89), with a short time interval from CRC to death (UC vs. CD: 6.5 (1-68) vs. 14.5 (8-40); p = 0.85; IBD: 12 months (1-68)). CRC occurring at a young age, a short time interval from the diagnosis of IBD to CRC-related death in the elderly, CRC-symptoms often mimicking IBD relapse and the observed high mortality rate may support the need of closer surveillance intervals in subgroups of patients.