scholarly journals A Significant Question in Cancer Risk and Therapy: Are Antibiotics Positive or Negative Effectors? Current Answers and Possible Alternatives

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 580 ◽  
Author(s):  
Steffanie S. Amadei ◽  
Vicente Notario
Keyword(s):  
Cancer Risk ◽  
Antibiotic Use ◽  
Developed Countries ◽  
Antibiotic Exposure ◽  
Epigenetic Alterations ◽  
Cancer Etiology ◽  
Intracellular Location ◽  
New Antibiotics ◽  
Environmental Disease ◽  
Therapeutic Protocols

Cancer is predominantly considered as an environmental disease caused by genetic or epigenetic alterations induced by exposure to extrinsic (e.g., carcinogens, pollutants, radiation) or intrinsic (e.g., metabolic, immune or genetic deficiencies). Over-exposure to antibiotics, which is favored by unregulated access as well as inappropriate prescriptions by physicians, is known to have led to serious health problems such as the rise of antibiotic resistance, in particular in poorly developed countries. In this review, the attention is focused on evaluating the effects of antibiotic exposure on cancer risk and on the outcome of cancer therapeutic protocols, either directly acting as extrinsic promoters, or indirectly, through interactions with the human gut microbiota. The preponderant evidence derived from information reported over the last 10 years confirms that antibiotic exposure tends to increase cancer risk and, unfortunately, that it reduces the efficacy of various forms of cancer therapy (e.g., chemo-, radio-, and immunotherapy alone or in combination). Alternatives to the current patterns of antibiotic use, such as introducing new antibiotics, bacteriophages or enzybiotics, and implementing dysbiosis-reducing microbiota modulatory strategies in oncology, are discussed. The information is in the end considered from the perspective of the most recent findings on the tumor-specific and intracellular location of the tumor microbiota, and of the most recent theories proposed to explain cancer etiology on the notion of regression of the eukaryotic cells and systems to stages characterized for a lack of coordination among their components of prokaryotic origin, which is promoted by injuries caused by environmental insults.

scholarly journals 2845. Oral Antibiotic Use and Risk of Colorectal Cancer in the UK, 1989–2012: A Matched Case–Control Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S68-S69
Author(s):  
Jiajia Zhang ◽  
Charles Haines ◽  
Alastair Watson ◽  
Andrew Hart ◽  
Mary Jane Platt ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Risk ◽  
Antibiotic Use ◽  
Tumor Location ◽  
Oral Antibiotic ◽  
Antibiotic Exposure ◽  
Colon Cancer Risk ◽  
Increased Risk ◽  
Matched Case ◽  
The Right

Abstract Background Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and CRC risk is lacking. Methods A matched case–control study (incident CRC cases and up to 5 matched controls) was conducted in the Clinical Practice Research Datalink (CPRD; 1989–2012). The CRPD is validated as 92% and 99% sensitive and specific for CRC detection (98% PPV). Antibiotic exposure [categorical and continuous terms (spline)] was investigated for risk pattern, stratified by tumor location, using conditional logistic regression and adjusting for known confounders. Results In total, 28,980 CRC cases and 137,077 controls were identified. Oral antibiotic use increased risk of colon cancer in a dose-dependent fashion (Ptrend < 0.001), but effects differed by anatomic location. Colon cancer risk was greatest in the proximal colon and with antibiotics with anti-anaerobic activity (Figure 1). In contrast, an inverse association was detected between antibiotic use and rectal cancers (Ptrend = 0.003), particularly with length of antibiotic exposure >60 days (adjusted odds ratio [AOR], 0.85, 95% CI 0.79–0.93) when compared with no antibiotic exposure. Nonlinearity models showed significantly increased colon cancer risk after minimal antibiotic use, but decreased rectum cancer risk with cumulative use of over 30 days (Figure 2). Penicillins, particularly ampicillin/amoxicillin, increased risk of colon cancer (AOR,1.09, [1.05–1.13]) whereas tetracyclines reduced risk for rectal cancer (AOR, 0.90, [0.84–0.97]). Significant interactions were detected between antibiotic use and tumor location (colon vs. rectum, Pinteraction < 0.001). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (AOR, 1.17, [1.06–1.31]). Conclusion We conclude that oral antibiotic use associates with increased colon cancer risk, particularly in the right colon, but a reduced risk for rectal cancer. This effect heterogeneity suggests unabsorbed antibiotics impact gut microbiota in the right colon to enhance carcinogenesis whereas antibiotic anti-inflammatory or anti-proliferative actions may yield an inverse effect on carcinogenesis in the rectum. Disclosures Sara E. Cosgrove, MD, MS, Basilea: Consultant; Theravance: Consultant.

scholarly journals Antibiotic exposure is associated with an increased risk of cancer: a systematic review and meta-analysis

2019 ◽  
Author(s):  
Yuting Li ◽  
Kaiyin He ◽  
Xiaojuan Peng ◽  
Chenxing Zhang ◽  
Lu Zhong ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Meta Analysis ◽  
Antibiotic Use ◽  
Epidemiological Studies ◽  
Antibiotic Exposure ◽  
Time Restrictions ◽  
Common Cancer ◽  
Increased Risk ◽  
Cancer Types ◽  
Risk Of Cancer

Abstract Background Several epidemiological studies have assessed the association between the use of antibiotics and cancer risk, but the results were inconsistent. Objective The objective of this study was to perform a meta-analysis to further evaluate possible association between antibiotic exposure and the risk of cancer. Methods We searched PubMed,Embase,Web of Science,and Chinese databases for studies on the association between antibiotic use and cancer without time restrictions. The risk estimates (hazard ratio (HR) or relative risk (RR) or Odds ratio (OR)) with their corresponding 95% confidence interval (CI) were calculated. Results A total of 23 observational studies with 19 case-control and 4 cohort studies were included in the meta-analysis. Exposure to antibiotics significantly increased the risk of cancer with an OR of 1.20 (95%CI 1.13-1.27, P=0.000). Subgroup meta-analysis by gender showed that the effect of antibiotic use on cancer risk was greater in male (34%) compared with that in female (19%). On the other hand, the risk of cancer increased with an increasing number of antibiotic prescriptions and the increasing cumulative days of antibiotic exposure. Moreover, of the 7 antibiotic types included, the six classes of antibiotics (penicillin, macrolides, quinolones, sulfonamides, tetracycline, cephalosporins) were associated with the increased risk of cancer. Further, of the 16 separate cancers included, exposure to antibiotics increased the risk of eight common cancer types (liver cancer, colorectal cancer, stomach and small intestine cancer, lymphomas, breast cancer, lung cancer, prostate cancer, and renal and bladder). Conclusions Exposure to common antibiotic types may increase the risk of the eight common cancer types in the studies population, especially in male, and the cancer risk increases with increasing antibiotic exposure intensity.

671 Update of a systematic review and meta-analysis studying the association between antibiotic use and clinical outcomes of non-small-cell lung cancer patients treated with immune checkpoint inhibitors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A708-A708
Author(s):  
Pierre-Alain Bandinelli ◽  
Julie Cervesi ◽  
Clément Le Bescop ◽  
Renaud Buffet ◽  
Jean De Gunzburg ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Outcomes ◽  
Time Window ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Antibiotic Use ◽  
Forest Plot ◽  
Antibiotic Exposure ◽  
Hazard Ratios

BackgroundImmune checkpoint inhibitors (ICIs) have been shown to improve patients‘ clinical outcomes in a variety of cancers, but with variable efficacy. Prior research has also suggested that systemic antibiotic (ABX) exposure may impact the intestinal microbiota and result in suboptimal ICI treatment outcomes. Our team published a systematic review and meta-analysis showing that ABX use could indeed decrease the survival of patients diagnosed with non-small-cell lung cancer (NSCLC) and treated with ICIs.1 The present abstract aims at updating this meta-analysis by incorporating new studies that have been published in the period ranging from September 2019 to August 2020.MethodsMedline (through PubMed), the Cochrane Library and major oncology conferences proceedings were systematically searched to identify studies assessing the impact of ABX use on the clinical outcomes of NSCLC patients treated with ICIs. Studies were found eligible for inclusion when they mentioned a hazard ratio (HR) or Kaplan–Meier curves for overall survival (OS) or progression-free survival (PFS) based on antibiotic exposure. Pooled HRs for OS and PFS and HRs for OS and PFS according to different time windows for ABX exposure were calculated.Results6 eligible new studies were identified between September 2019 and August 2020 while 3 other studies were updated with new information. Altogether, 27 studies reported data for OS (6,436 patients, 826 of whom coming from new studies) and 24 for PFS (3,751 patients, 786 of whom coming from new studies). The pooled HR was 1.75 (95% confidence interval [CI]: 1.38–2.23) for OS and 1.57 (95% CI: 1.28–1.92) for PFS, confirming a significantly reduced survival in patients with NSCLC exposed to ABX. The detailed analysis in subgroups based on the time window of exposure (figure 1, figure 2) suggests that the deleterious effect of ABX is stronger when the exposition happens shortly before and after the initiation of the ICI treatment.Abstract 671 Figure 1Forest plot of hazard ratios for overall survival of patients diagnosed with NSCLC and exposed to antibiotics versus not exposed to antibiotics, according to the time window of antibiotic exposureAbstract 671 Figure 2Forest plot of hazard ratios for progression-free survival of patients diagnosed with NSCLC and exposed to antibiotics versus not exposed to antibiotics, according to the time window of antibiotic exposureConclusionsThe update of the meta-analysis confirms the previously reported deleterious effect of ABX on ICI treatment outcomes, taking into account the latest publications in the field. The topic deserves further research to uncover if the effect will stand with 1st line use of ICI together with chemotherapies and/or other approved combinations, elucidate the mechanisms at stake and improve care of patients.ReferencesLurienne L, Cervesi J, Duhalde L, de Gunzburg J, Andremont A, Zalcman G, et al. NSCLC immunotherapy efficacy and antibiotic use: a systematic review and meta-analysis. J Thorac Oncol 2020;15:1147–1159.

scholarly journals Cancer Risk Assessment and Screening; A Challenge for Clinical Pathology Service?

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Siti Boedina Kresno
Keyword(s):  
Risk Factors ◽  
Cancer Risk ◽  
Hereditary Cancer ◽  
Cancer Susceptibility ◽  
Intrinsic Factor ◽  
Cancer Risk Assessment ◽  
Prophylactic Surgery ◽  
Cancer Etiology ◽  
Cancer Burden ◽  
Cancer Susceptibility Genes

There is evidence demonstrating that cancer etiology is multi-factorial and modification of risk factors has achievedcancer prevention. There is therefore a need to advance the understanding of cancer etiology through interaction effectsbetween risk factors when estimating the contribution of an individual to the cancer burden in a population. It has beenknown that cancer may arise from genetic susceptibility to the disease as an intrinsic factor; however, non-intrinsic factorsdrive most cancer risk as well and highlight the need for cancer prevention. Are our clinical pathologists aware of thesefacts?. Are they ready to understand and to provide an excellent test with good expertise?. Hereditary cancer testing istypically performed using gene panels, which may be either cancer-specific or pan-cancer to assess risk for a defined orbroader range of cancers, respectively. Given the clinical implications of hereditary cancer testing, diagnostic laboratoriesmust develop high-quality panel tests, which serve a broad, genetically diverse patient population. The result will determinea patient's eligibility for targeted therapy, for instance, or lead a patient to prophylactic surgery, chemoprevention, andsurveillance. This review will introduce the definitions of intrinsic and non-intrinsic risk factors, which have been employed inrecent work and how evidence for their effects on the cancer burden in human subjects has been obtained. Genetic testingof cancer susceptibility genes by use of liquid biopsies and New Generation Sequencing (NGS) is now widely applied inclinical practice to predict the risk of developing cancer, help diagnosis, and treatment monitoring.

scholarly journals Total and added sugar intakes, sugar types, and cancer risk: results from the prospective NutriNet-Santé cohort

2020 ◽  
Vol 112 (5) ◽  
pp. 1267-1279 ◽  
Author(s):  
Charlotte Debras ◽  
Eloi Chazelas ◽  
Bernard Srour ◽  
Emmanuelle Kesse-Guyot ◽  
Chantal Julia ◽  
...  
Keyword(s):  
Risk Factor ◽  
Weight Gain ◽  
Cancer Risk ◽  
Current Debate ◽  
Cancer Etiology ◽  
Added Sugar ◽  
Added Sugars ◽  
Sugar Intake ◽  
Sugary Drinks

ABSTRACT Background Excessive sugar intake is now recognized as a key risk factor for obesity, type 2 diabetes, and cardiovascular diseases. In contrast, evidence on the sugar–cancer link is less consistent. Experimental data suggest that sugars could play a role in cancer etiology through obesity but also through inflammatory and oxidative mechanisms and insulin resistance, even in the absence of weight gain. Objective The objective was to study the associations between total and added sugar intake and cancer risk (overall, breast, and prostate), taking into account sugar types and sources. Methods In total, 101,279 participants aged &gt;18 y (median age, 40.8 y) from the French NutriNet-Santé prospective cohort study (2009–2019) were included (median follow-up time, 5.9 y). Sugar intake was assessed using repeated and validated 24-h dietary records, designed to register participants’ usual consumption for &gt;3500 food and beverage items. Associations between sugar intake and cancer risk were assessed by Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). Results Total sugar intake was associated with higher overall cancer risk (n = 2503 cases; HR for quartile 4 compared with quartile 1: 1.17; 95% CI: 1.00, 1.37; Ptrend = 0.02). Breast cancer risks were increased (n = 783 cases; HRQ4vs.Q1 = 1.51; 95% CI: 1.14, 2.00; Ptrend = 0.0007). Results remained significant when weight gain during follow-up was adjusted for. In addition, significant associations with cancer risk were also observed for added sugars, free sugars, sucrose, sugars from milk-based desserts, dairy products, and sugary drinks (Ptrend ≤ 0.01). Conclusions These results suggest that sugars may represent a modifiable risk factor for cancer prevention (breast in particular), contributing to the current debate on the implementation of sugar taxation, marketing regulation, and other sugar-related policies. This trial was registered at clinicaltrials.gov as NCT03335644.

scholarly journals 4444 The effect of early life antibiotics on gut microbiome and fecal bile acid concentrations in children

2020 ◽  
Vol 4 (s1) ◽  
pp. 146-147
Author(s):  
Alain Jesus Benitez ◽  
Jeffrey S. Gerber ◽  
Ceylan Tanes ◽  
Kyle Bittinger ◽  
Elliot S. Friedman ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bile Acid ◽  
Early Life ◽  
Bacterial Community Composition ◽  
Antibiotic Use ◽  
First Year ◽  
Antibiotic Exposure ◽  
Fecal Bile Acid ◽  
Gi Symptoms ◽  
First Year Of Life

OBJECTIVES/GOALS: The current proposal seeks to investigate the effect of early life antibiotic use in the development of functional gastrointestinal (GI) disorders. We propose that infants exposed to antibiotics will present with gut microbial dysbiosis, changes in fecal bile acid concentrations and develop more GI symptoms compared to unexposed children. METHODS/STUDY POPULATION: We analyzed fecal samples from 174 subjects at 12 months of age, of whom 52 were exposed to antibiotics in their first year of life. Of these, 33 subjects were sampled again at 24 months of age. DNA from 200mg of frozen stool (−80C) was isolated with the Qiagen DNeasy PowerSoil kit. Shotgun libraries were generated using the NexteraXT kit and sequenced on the Illumina HiSeq 2500 using 2x125 bp chemistry. Sequence data were analyzed using the Sunbeam metagenomics pipeline. The abundance of bacteria was estimated using Kraken version 2.0.8. Fecal bile acids will be quantified by liquid chromatography–mass spectrometry (LC-MS). RESULTS/ANTICIPATED RESULTS: Overall bacterial community composition at 12 or 24 months was not associated with antibiotic exposure (PERMANOVA test, Bray-Curtis distance). An increase in Enterobacteriaceae, in particular Escherichia coli, is a signature of antibiotic-induced dysbiosis, but also of early infant gut. Children with antibiotic exposure had slightly higher abundance of Escherichia coli compared to those with no exposure (p = 0.03). At 24 months, the abundance of Bacteroides caccae, a commensal gut species, was decreased for children exposed to antibiotics in the first year of life (fdr = 0.02). We will perform further analysis of bile acid modifying bacteria, fecal bile acid concentrations and correlate to GI symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest a significant but nuanced impact of early life antibiotic use on the composition of the gut microbiota. The association of antibiotic exposure with B. caccae and E. coli warrant further attention in the context of the rapidly developing early-life microbiome. CONFLICT OF INTEREST DESCRIPTION: The authors declare no conflicts of interest relevant to this work.

scholarly journals Progesterone and Breast Cancer

2019 ◽  
Vol 41 (2) ◽  
pp. 320-344 ◽  
Author(s):  
Britton Trabert ◽  
Mark E Sherman ◽  
Nagarajan Kannan ◽  
Frank Z Stanczyk
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Normal Breast ◽  
Cancer Etiology ◽  
Progesterone Metabolites ◽  
Breast Physiology ◽  
Independent Effects ◽  
The Individual

Abstract Synthetic progestogens (progestins) have been linked to increased breast cancer risk; however, the role of endogenous progesterone in breast physiology and carcinogenesis is less clearly defined. Mechanistic studies using cell culture, tissue culture, and preclinical models implicate progesterone in breast carcinogenesis. In contrast, limited epidemiologic data generally do not show an association of circulating progesterone levels with risk, and it is unclear whether this reflects methodologic limitations or a truly null relationship. Challenges related to defining the role of progesterone in breast physiology and neoplasia include: complex interactions with estrogens and other hormones (eg, androgens, prolactin, etc.), accounting for timing of blood collections for hormone measurements among cycling women, and limitations of assays to measure progesterone metabolites in blood and progesterone receptor isotypes (PRs) in tissues. Separating the individual effects of estrogens and progesterone is further complicated by the partial dependence of PR transcription on estrogen receptor (ER)α-mediated transcriptional events; indeed, interpreting the integrated interaction of the hormones may be more essential than isolating independent effects. Further, many of the actions of both estrogens and progesterone, particularly in “normal” breast tissues, are driven by paracrine mechanisms in which ligand binding to receptor-positive cells evokes secretion of factors that influence cell division of neighboring receptor-negative cells. Accordingly, blood and tissue levels may differ, and the latter are challenging to measure. Given conflicting data related to the potential role of progesterone in breast cancer etiology and interest in blocking progesterone action to prevent or treat breast cancer, we provide a review of the evidence that links progesterone to breast cancer risk and suggest future directions for filling current gaps in our knowledge.

Abstract 4460: Precision cancer risk diagnosis by accumulation of epigenetic alterations

2016 ◽  
Author(s):  
Toshikazu Ushijima ◽  
Kiyoshi Asada ◽  
Masahiro Maeda ◽  
Takeshi Nakajima ◽  
Taichi Shimazu
Keyword(s):  
Cancer Risk ◽  
Epigenetic Alterations

scholarly journals Epigenetics and Neurological Disorders in ART

2019 ◽  
Vol 20 (17) ◽  
pp. 4169
Author(s):  
Marina La Rovere ◽  
Marica Franzago ◽  
Liborio Stuppia
Keyword(s):  
Neurological Disorders ◽  
Assisted Reproductive Technologies ◽  
Current Knowledge ◽  
Developed Countries ◽  
Reproductive Technologies ◽  
Epigenetic Modifications ◽  
Epigenetic Alterations ◽  
Long Term Effects ◽  
Increased Risk

About 1–4% of children are currently generated by Assisted Reproductive Technologies (ART) in developed countries. These babies show only a slightly increased risk of neonatal malformations. However, follow-up studies have suggested a higher susceptibility to multifactorial, adult onset disorders like obesity, diabetes and cardiovascular diseases in ART offspring. It has been suggested that these conditions could be the consequence of epigenetic, alterations, due to artificial manipulations of gametes and embryos potentially able to alter epigenetic stability during zygote reprogramming. In the last years, epigenetic alterations have been invoked as a possible cause of increased risk of neurological disorders, but at present the link between epigenetic modifications and long-term effects in terms of neurological diseases in ART children remains unclear, due to the short follow up limiting retrospective studies. In this review, we summarize the current knowledge about neurological disorders promoted by epigenetics alterations in ART. Based on data currently available, it is possible to conclude that little, if any, evidence of an increased risk of neurological disorders in ART conceived children is provided. Most important, the large majority of reports appears to be limited to epidemiological studies, not providing any experimental evidence about epigenetic modifications responsible for an increased risk.

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