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Gastroenterology Mar 2022Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC), despite decreases in CRC incidence in recent years. Chronic... (Review)
Review
Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC), despite decreases in CRC incidence in recent years. Chronic inflammation is the driver of neoplastic progression, resulting in dysplastic precursor lesions that may arise in multiple areas of the colon through a process of field cancerization. Colitis-associated CRC shares many molecular similarities with sporadic CRC, and preclinical investigations have demonstrated a potential role for the microbiome in concert with the host immune system in the development of colitis-associated colorectal cancer (CAC). Some unique molecular differences occur in CAC, but their role in the pathogenesis and behavior of inflammation-associated cancers remains to be elucidated. Nonconventional types of dysplasia have been increasingly recognized, but their natural history is not well defined, and they have not been incorporated into surveillance algorithms. The concept of cumulative inflammatory burden highlights the importance of considering histologic inflammation over time as an important risk factor for CAC. Dysplasia is arguably the most important risk factor for developing CAC, and advances have been made in the endoscopic detection and removal of precancerous lesions, thereby deferring or avoiding surgical resection. Some of the agents used to treat IBD are chemopreventive. It is hoped that by gaining better control of the underlying inflammation with newer medications and better endoscopic detection and management, a more sophisticated appreciation of clinicopathologic risk factors, and growing awareness of the genetic, immunologic, and environmental causes of colitis- associated neoplasia, that colitis-associated colorectal neoplasia will become even more predictable and manageable in the coming years.
Topics: Chemoprevention; Colectomy; Colitis, Ulcerative; Colorectal Neoplasms; Crohn Disease; Endoscopy, Gastrointestinal; Population Surveillance; Primary Prevention; Risk Factors
PubMed: 34757143
DOI: 10.1053/j.gastro.2021.10.035 -
Molecular Oncology Mar 2021An estimated 30-40% of cancers can be prevented through changes in modifiable lifestyle and environmental risk factors known to be associated with cancer incidence.... (Review)
Review
An estimated 30-40% of cancers can be prevented through changes in modifiable lifestyle and environmental risk factors known to be associated with cancer incidence. Despite this knowledge, there remains limited awareness that these associations exist. The purpose of this review article was to summarize the epidemiologic evidence concerning the contribution of physical activity, sedentary behavior, and obesity to cancer etiology and to provide an overview of the biologic mechanisms that may be operative between these factors and cancer incidence. Strong and consistent evidence exists that higher levels of physical activity reduce the risk of six different cancer sites (bladder, breast, colon, endometrial, esophageal adenocarcinoma, gastric cardia), whereas moderate evidence inversely associates physical activity with lung, ovarian, pancreatic and renal cancer, and limited evidence inversely correlates physical activity with prostate cancer. Sedentary behavior, independent of physical activity, has been shown to increase the risk of colon, endometrial, and lung cancers. Obesity is an established risk factor for 13 different cancer sites (endometrial, postmenopausal breast, colorectal, esophageal, renal/kidneys, meningioma, pancreatic, gastric cardia, liver, multiple myeloma, ovarian, gallbladder, and thyroid). The main biologic mechanisms whereby physical activity, sedentary behavior, and obesity are related to cancer incidence include an effect on endogenous sex steroids and metabolic hormones, insulin sensitivity, and chronic inflammation. Several emerging pathways related to oxidative stress, DNA methylation, telomere length, immune function, and gut microbiome are presented. Key recommendations for future research in both the epidemiology and biology of the associations between physical activity, sedentary behavior, obesity, and cancer risk are also provided.
Topics: Animals; Exercise; Humans; Incidence; Neoplasms; Obesity; Protective Factors; Risk Factors; Sedentary Behavior
PubMed: 32741068
DOI: 10.1002/1878-0261.12772 -
Annals of Agricultural and... Mar 2019The cancerous process is result of disturbed cell function. This is due to the accumulation of many genetic and epigenetic changes within the cell, expressed in the... (Review)
Review
The cancerous process is result of disturbed cell function. This is due to the accumulation of many genetic and epigenetic changes within the cell, expressed in the accumulation of chromosomal or molecular aberrations, which leads to genetic instability. It is difficult to assess the validity of individual aetiological factors, but it can be concluded that interaction of various risk factors has the largest contribution to the cancer development. Environmental, exogenous and endogenous factors as well as individual factors, including genetic predisposition contribute to the development of cancer. Epidemiological research on the development of malignant tumors has focused over the years on the determinants of environmental and genetic factors of cancer incidence and mortality rate. According to current state of knowledge, 80-90% of malignant tumors are caused by external environmental factors (carcinogens). Epidemiological studies have proved that the main factors responsible for the development of malignant neoplasia among humans are environmental factors arising from human behaviour. It has been confirmed that smoking, excessive alcohol consumption, diet, and reproductive behaviour are important for the development of malignant neoplasia in the human population. According to the World Health Organization, in 2020 we may expect about 10 million deaths, including 7-8 million in the developing countries, while this number in the developed countries will not change and will be 2-3 million. The aim this study was systematization of knowledge concerning the risk factors of malignant tumours and supplementing them with the latest research results.
Topics: Carcinogens, Environmental; Genetic Predisposition to Disease; Humans; Life Style; Neoplasms; Risk Factors
PubMed: 30922021
DOI: 10.26444/aaem/94299 -
The Journal of Pathology Jul 2022Breast cancer affects one in seven women worldwide during their lifetime. Widespread mammographic screening programs and education campaigns allow for early detection of... (Review)
Review
Breast cancer affects one in seven women worldwide during their lifetime. Widespread mammographic screening programs and education campaigns allow for early detection of the disease, often during its asymptomatic phase. Current practice in treatment and recurrence monitoring is based primarily on pathological evaluations but can also encompass genomic evaluations, both of which focus on the primary tumor. Although breast cancer is one of the most studied cancers, patients still recur at a rate of up to 15% within the first 10 years post-surgery. Local recurrence was originally attributed to tumor cells contaminating histologically normal (HN) tissues beyond the surgical margin, but advances in technology have allowed for the identification of distinct aberrations that exist in the peri-tumoral tissues themselves. One leading theory to explain this phenomenon is the field cancerization theory. Under this hypothesis, tumors arise from a field of molecularly altered cells that create a permissive environment for malignant evolution, which can occur with or without morphological changes. The traditional histopathology paradigm dictates that molecular alterations are reflected in the tissue phenotype. However, the spectrum of inter-patient variability of normal breast tissue may obfuscate recognition of a cancerized field during routine diagnostics. In this review, we explore the concept of field cancerization focusing on HN peri-tumoral tissues: we present the pathological and molecular features of field cancerization within these tissues and discuss how the use of peri-tumoral tissues can affect research. Our observations suggest that pathological and molecular evaluations could be used synergistically to assess risk and guide the therapeutic management of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Breast; Breast Neoplasms; Early Detection of Cancer; Female; Humans; United Kingdom
PubMed: 35362092
DOI: 10.1002/path.5902 -
The Proceedings of the Nutrition Society Aug 2019Menopause, the permanent cessation of the menstrual cycle, marks the end of a woman's reproductive lifespan. In addition to changes in sex hormone levels associated with... (Review)
Review
Menopause, the permanent cessation of the menstrual cycle, marks the end of a woman's reproductive lifespan. In addition to changes in sex hormone levels associated with menopause, its timing is another predictor of future health outcomes such as duration of the presence of vasomotor symptoms (VMS) and the risk of hormone-related cancers. With ageing of the population, it is estimated that worldwide 1·2 billion women will be menopausal by the year 2030. Previously the effects of reproductive factors (e.g. parity, age at menarche, pregnancy) and socio-demographic factors on intermediate and long-term health outcomes of menopause have been widely documented. However, little is known about whether diet could have an impact on these. Therefore, we review current evidence on the associations of diet with menopause, presence of VMS and the risk of hormone-related cancers such as ovarian, endometrial and breast cancer. Dietary factors could influence the lifespan of the ovaries and sex-hormones levels, hence the timing of natural menopause. Few studies reported an association between diet, in particular soya consumption, and a reduced risk of VMS. Sustained oestrogen exposure has been associated with a higher risk of hormone-related cancers and thus high-fat and meat diets have been linked with an increased risk of these cancers. However, to better understand the mechanistic pathways involved and to make stronger conclusions for these relationships, further studies investigating the associations of dietary intakes and dietary patterns with menopause, presence of VMS and the risk of hormone-related cancers are required.
Topics: Breast Neoplasms; Diet; Endometrial Neoplasms; Female; Humans; Menopause; Middle Aged; Ovarian Neoplasms; Risk Factors
PubMed: 30706844
DOI: 10.1017/S0029665118002884 -
Diabetes Care Nov 2012Available evidence supports the emerging hypothesis that metabolic syndrome may be associated with the risk of some common cancers. We did a systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Available evidence supports the emerging hypothesis that metabolic syndrome may be associated with the risk of some common cancers. We did a systematic review and meta-analysis to assess the association between metabolic syndrome and risk of cancer at different sites.
RESEARCH DESIGN AND METHODS
We conducted an electronic search for articles published through October 2011 without restrictions and by reviewing reference lists from retrieved articles. Every included study was to report risk estimates with 95% CIs for the association between metabolic syndrome and cancer.
RESULTS
We analyzed 116 datasets from 43 articles, including 38,940 cases of cancer. In cohort studies in men, the presence of metabolic syndrome was associated with liver (relative risk 1.43, P < 0.0001), colorectal (1.25, P < 0.001), and bladder cancer (1.10, P = 0.013). In cohort studies in women, the presence of metabolic syndrome was associated with endometrial (1.61, P = 0.001), pancreatic (1.58, P < 0.0001), breast postmenopausal (1.56, P = 0.017), rectal (1.52, P = 0.005), and colorectal (1.34, P = 0.006) cancers. Associations with metabolic syndrome were stronger in women than in men for pancreatic (P = 0.01) and rectal (P = 0.01) cancers. Associations were different between ethnic groups: we recorded stronger associations in Asia populations for liver cancer (P = 0.002), in European populations for colorectal cancer in women (P = 0.004), and in U.S. populations (whites) for prostate cancer (P = 0.001).
CONCLUSIONS
Metabolic syndrome is associated with increased risk of common cancers; for some cancers, the risk differs betweens sexes, populations, and definitions of metabolic syndrome.
Topics: Female; Humans; Male; Metabolic Syndrome; Neoplasms; Risk Factors; Sex Factors
PubMed: 23093685
DOI: 10.2337/dc12-0336 -
BMC Cancer Dec 2021Previous large observational cohort studies showed higher blood pressure (BP) positively associated with cancer. We used Mendelian randomization (MR) to obtain less... (Observational Study)
Observational Study
BACKGROUND
Previous large observational cohort studies showed higher blood pressure (BP) positively associated with cancer. We used Mendelian randomization (MR) to obtain less confounded estimates of BP on total and site-specific cancers.
METHODS
We applied replicated genetic instruments for systolic and diastolic BP to summary genetic associations with total cancer (37387 cases, 367856 non-cases) from the UK Biobank, and 17 site-specific cancers (663-17881 cases) from a meta-analysis of the UK Biobank and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging. We used inverse-variance weighting with multiplicative random effects as the main analysis, and sensitivity analyses including the weighted median, MR-Egger and multivariable MR adjusted for body mass index and for smoking. For validation, we included breast (Breast Cancer Association Consortium: 133384 cases, 113789 non-cases), prostate (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome Consortium: 79194 cases, 61112 non-cases) and lung (International Lung and Cancer Consortium: 10246 cases, 38295 non-cases) cancer from large consortia. We used asthma as a negative control outcome.
RESULTS
Systolic and diastolic BP were unrelated to total cancer (OR 0.98 per standard deviation higher [95% confidence interval (CI) 0.89, 1.07] and OR 1.00 [95% CI 0.92, 1.08]) and to site-specific cancers after accounting for multiple testing, with consistent findings from consortia. BP was nominally associated with melanoma and possibly kidney cancer, and as expected, not associated with asthma. Sensitivity analyses using other MR methods gave similar results.
CONCLUSIONS
In contrast to previous observational evidence, BP does not appear to be a risk factor for cancer, although an effect on melanoma and kidney cancer cannot be excluded. Other targets for cancer prevention might be more relevant.
Topics: Blood Pressure; Genetic Association Studies; Humans; Mendelian Randomization Analysis; Neoplasms; Odds Ratio; Risk Factors
PubMed: 34915881
DOI: 10.1186/s12885-021-09067-x -
BMJ (Clinical Research Ed.) Nov 2020To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Published studies in Medline from 1 January 2000 to 10 April 2020.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models.
RESULTS
The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings.
CONCLUSIONS
Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.
Topics: Humans; Neoplasms; Risk Factors; Survival Analysis; Time-to-Treatment
PubMed: 33148535
DOI: 10.1136/bmj.m4087 -
International Journal of Epidemiology Jun 2023Genetic and lifestyle factors are associated with cancer risk. We investigated the benefits of adhering to lifestyle advice by the World Cancer Research Fund (WCRF) with...
BACKGROUND
Genetic and lifestyle factors are associated with cancer risk. We investigated the benefits of adhering to lifestyle advice by the World Cancer Research Fund (WCRF) with the risk of 13 types of cancer and whether these associations differ according to genetic risk using data from the UK Biobank.
METHODS
In 2006-2010, participants aged 37-73 years had their lifestyle assessed and were followed up for incident cancers until 2015-2019. Analyses were restricted to those of White European ancestry with no prior history of malignant cancer (n = 195 822). Polygenic risk scores (PRSs) were computed for 13 cancer types and these cancers combined ('overall cancer'), and a lifestyle index was calculated from WCRF recommendations. Associations with cancer incidence were estimated using Cox regression, adjusting for relevant confounders. Additive and multiplicative interactions between lifestyle index and PRSs were assessed.
RESULTS
There were 15 240 incident cancers during the 1 926 987 person-years of follow-up (median follow-up = 10.2 years). After adjusting for confounders, the lifestyle index was associated with a lower risk of overall cancer [hazard ratio per standard deviation increase (95% CI) = 0.89 (0.87, 0.90)] and of eight specific cancer types. There was no evidence of interactions on the multiplicative scale. There was evidence of additive interactions in risks for colorectal, breast, pancreatic, lung and bladder cancers, such that the recommended lifestyle was associated with greater change in absolute risk for persons at higher genetic risk (P < 0.0003 for all).
CONCLUSIONS
The recommended lifestyle has beneficial associations with most cancers. In terms of absolute risk, the protective association is greater for higher genetic risk groups for some cancers. These findings have important implications for persons most genetically predisposed to those cancers and for targeted strategies for cancer prevention.
Topics: Humans; Incidence; Prospective Studies; Risk Factors; Life Style; Neoplasms
PubMed: 36651198
DOI: 10.1093/ije/dyac238 -
JAMA Network Open Nov 2019Marijuana use is common and growing in the United States amid a trend toward legalization. Exposure to tobacco smoke is a well-described preventable cause of many... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Marijuana use is common and growing in the United States amid a trend toward legalization. Exposure to tobacco smoke is a well-described preventable cause of many cancers; the association of marijuana use with the development of cancer is not clear.
OBJECTIVE
To assess the association of marijuana use with cancer development.
DATA SOURCES
A search of PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library was conducted on June 11, 2018, and updated on April 30, 2019. A systematic review and meta-analysis of studies published from January 1, 1973, to April 30, 2019, and references of included studies were performed, with data analyzed from January 2 through October 4, 2019.
STUDY SELECTION
English-language studies involving adult marijuana users and reporting cancer development. The search strategy contained the following 2 concepts linked together with the AND operator: marijuana OR marihuana OR tetrahydrocannabinol OR cannabinoid OR cannabis; AND cancer OR malignancy OR carcinoma OR tumor OR neoplasm.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently reviewed titles, abstracts, and full-text articles; 3 reviewers independently assessed study characteristics and graded evidence strength by consensus.
MAIN OUTCOMES AND MEASURES
Rates of cancer in marijuana users, with ever use defined as at least 1 joint-year exposure (equivalent to 1 joint per day for 1 year), compared with nonusers. Meta-analysis was conducted if there were at least 2 studies of the same design addressing the same cancer without high risk of bias when heterogeneity was low to moderate for the following 4 cancers: lung, head and neck squamous cell carcinoma, oral squamous cell carcinoma, and testicular germ cell tumor (TGCT), with comparisons expressed as odds ratios (ORs) with 95% CIs.
RESULTS
Twenty-five English-language studies (19 case-control, 5 cohort, and 1 cross-sectional) were included; few studies (n = 2) were at low risk of bias. In pooled analysis of case-control studies, ever use of marijuana was not associated with head and neck squamous cell carcinoma or oral cancer. In pooled analysis of 3 case-control studies, more than 10 years of marijuana use (joint-years not reported) was associated with TGCT (OR, 1.36; 95% CI, 1.03-1.81; P = .03; I2 = 0%) and nonseminoma TGCT (OR, 1.85; 95% CI, 1.10-3.11; P = .04; I2 = 0%). Evaluations of ever use generally found no association with cancers, but exposure levels were low and poorly defined. Findings for lung cancer were mixed, confounded by few marijuana-only smokers, poor exposure assessment, and inadequate adjustment; meta-analysis was not performed for several outcomes.
CONCLUSIONS AND RELEVANCE
Low-strength evidence suggests that smoking marijuana is associated with developing TGCT; its association with other cancers and the consequences of higher levels of use are unclear. Long-term studies in marijuana-only smokers would improve understanding of marijuana's association with lung, oral, and other cancers.
TRIAL REGISTRATION
PROSPERO identifier: CRD42018102457.
Topics: Humans; Marijuana Use; Neoplasms; Risk Factors
PubMed: 31774524
DOI: 10.1001/jamanetworkopen.2019.16318