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ABSTRACT The tobacco epidemic has been one of the biggest public health threats, and smoking is one of the world's largest preventable causes of premature death. An estimated 15.4% of all deaths in the world are attributable to tobacco smoking. The present review aims to describe addiction to tobacco smoking and vaping. Tobacco and vaping devices contain nicotine, a highly addictive drug, which explains why smoking is so prevalent and persistent. Electronic cigarettes are a group of novel nicotine or tobacco products that have rapidly gained popularity in recent years. Electronic cigarette devices allow for the use of other drugs, including THC, while the lax regulation may allow for the introduction of toxic compounds that can lead to acute or subacute toxicity, such as the e-cigarette- or vaping-associated lung injury that has been linked to vitamin E acetate. In addition, regular vapers and heated tobacco devices emit toxins, although at lower concentrations than burned tobacco. However, more and more side effects have been identified. No new effective treatment for nicotine addiction has been developed recently, despite its huge adverse impact on overall health and other outcomes. As for the primary line of medications, the last one started in 2006, the varenicline, demonstrating a low interest in developing new medications against smoking, an unacceptable state of affairs, given the huge impact of smoking on morbidity and mortality.
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Drug-induced liver injury (DILI) risk prediction, diagnosis establishment, clinical management, and all other aspects are facing great challenges. Although the current understanding of its pathogenesis is still incomplete, research over the past 20 years has shown that genetic susceptibility may play an important role in the occurrence and development of DILI. In recent years, pharmacogenomics studies have further revealed the association between human leukocyte antigen (HLA) genes, some non-HLA genes, and hepatotoxicity from certain drugs. However, due to the lack of well-designed, prospective, large-sample cohort validation and low positive predictive values, there may still be some way to go before the current results can be truly translated into clinical practice for precise prediction and prevention of DILI risk.
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Humans , Genetic Predisposition to Disease , Prospective Studies , Risk Factors , Chemical and Drug Induced Liver Injury/genetics , Drug-Related Side Effects and Adverse Reactions , LiverABSTRACT
Abstract Objectives: Abdominal Aortic Aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. This study aimed to examine the potential association of the +276G/T and −420C>G polymorphisms in the resistin gene with AAA susceptibility and progression. Method: We performed a retrospective study involving AAA patients and healthy controls, assessing the distribution of the +276G/T and −420C>G genotypes in both groups. Hardy-Weinberg equilibrium was assessed for both polymorphisms. Logistic regression was used to explore the influence of these genotypes on AAA occurrence and progression, adjusting for relevant confounders. Results: The distribution of +276G/T polymorphism did not significantly differ between AAA patients and controls. Conversely, a significant difference was observed in the genotype distribution of −420C>G polymorphism between the two groups. The CC genotype and CC/CG genotypes of −420C>G polymorphism were found to be associated with an increased risk and progression of AAA. Conclusions: The −420C>G polymorphism, particularly the CC genotype and CC/CG genotypes, might play a substantial role in AAA susceptibility and progression. The present findings underscore the need for further investigations to confirm these associations and fully elucidate the role of the resistin gene in AAA.
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RESUMEN Introducción: El cáncer de pulmón es uno de los principales problemas de salud en Cuba y el mundo. Las diferencias genéticas a causa de polimorfismos de un solo nucleótido, son factores importantes involucrados en la susceptibilidad genética a esta enfermedad. En Cuba son escasos los datos disponibles sobre los polimorfismos de un solo nucleótido y su posible influencia sobre la aparición y pronóstico del cáncer. Objetivo: Exponer la importancia del estudio de los polimorfismos de un solo nucleótido en genes de la reparación del daño al ADN en el cáncer de pulmón. Desarrollo: El tabaquismo es el principal factor de riesgo para desarrollar cáncer de pulmón, sin embargo, aproximadamente el 15 % de los fumadores desarrollará la enfermedad. Los polimorfismos de un solo nucleótido son factores involucrados en la predisposición genética a las enfermedades. La presencia de variantes polimórficas puede modificar la eficacia de los sistemas de reparación, favoreciendo la aparición de genotoxicidad y/o mutagénesis. También pueden modificar la respuesta a los tratamientos oncológicos y la supervivencia de los pacientes. Por consiguiente, además de ser marcadores de susceptibilidad, los polimorfismos se consideran marcadores de pronóstico individual de respuesta a la terapia. Este trabajo enfatiza la utilidad de su evaluación como biomarcadores clínicos y de susceptibilidad genética a enfermedades en la población cubana. Conclusiones: El estudio de polimorfismos de un solo nucleótido permitirá el abordaje personalizado de enfermedades oncológicas, lo cual podría contribuir a su detección temprana y a definir grupos de individuos con alto riesgo de padecer cáncer de pulmón.
ABSTRACT Introduction: Lung cancer is one of the main health problems in Cuba and worldwide. Genetic differences due to single nucleotide polymorphisms are important factors involved in the genetic susceptibility to this disease. In Cuba, there are scarce data available on single nucleotide polymorphisms and their possible influence on the incidence and prognosis of cancer. Objective: To expose the importance of the study of single nucleotide polymorphisms in DNA damage repair genes in lung cancer. Results: Smoking is the main risk factor for developing lung cancer, however, approximately 15 % of smokers will develop the disease. Single nucleotide polymorphisms are important factors involved in genetic predisposition to diseases. The presence of polymorphic variants can modify the efficacy of repair systems, favoring the occurrence of genotoxicity and/or mutagenesis. They can also modify the response to oncological treatments and patient´s survival. Therefore, in addition to being susceptibility markers, polymorphisms are considered individual prognostic markers of response to therapy. This work emphasizes the usefulness of evaluating single nucleotide polymorphisms as clinical and susceptibility biomarkers in the Cuban population. Conclusions. The study of single nucleotide polymorphisms will allow a personalized approach to oncological diseases, which could contribute to define groups of individuals at high risk of getting lung cancer, therefore, early disease detection.
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Hereditary breast cancer refers to malignant tumors caused by pathogenic germline mutations of breast cancer susceptibility genes (BRCA). At present, it is believed that BRCA1/2 genes are most closely related to the development of hereditary breast cancer. Mutation will lead to loss of normal function, instability of genome, and then lead to tumorigenesis. Especially for those with germline mutations, not only the risk of breast cancer will be greatly increased, but also the probability of ovarian cancer and other cancers will be increased. With the emergence and clinical application of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, BRCA1/2 genes have been regarded as new targets for the treatment of breast cancer. This article reviews the latest research of breast cancer with BRCA1/2 gene mutations.
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The lens of the eye has been recognized as one of the most radiosensitive tissues. It has been known that a radiation dose of 0.5 Gy or higher can induce radiation cataract. Studies have also demonstrated that long-term exposure to low-dose radiation can increase the risk of lens opacity. However, the specific biologic mechanism of lens opacity induced by low-dose ionizing radiation is still unclear. Many mechanism chains may induce opacity independently or jointly, such as genomic damage in lens epithelial cells, oxidative stress, defects in intercellular communication, and inflammatory reaction, and genetic and epigenetic factors may also play a role. This paper briefly reviews the mechanisms of low-dose ionizing radiation inducing lens opacity as well as the role of genetic susceptibility in its development and progression, in order to provide a scientific reference for the prevention and control of this disease.
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Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characterized by chronic inflammatory arthritis of unknown cause, lasting six weeks or longer, and accompanied by organ damages. It is the most common chronic inflammatory rheumatic disease in childhood with unclear aetiology. A20, a protein encoded by the tumor necrosis factor α-induced protein 3 gene (TNFAIP3), regulates cell inflammatory response and apoptosis through suppressing inflammatory NF-κB signaling by acting as an ubiquitin-editing enzyme. NOD-like receptor protein 3 (NLRP3) inflammasome, a multiprotein complex formed by a subgroup of intracellular pattern recognition receptors, mediates the activation of caspase-1 and the secretion of proinflammatory cytokines IL-1β and IL-18 in response to microbial infection and cellular damage. A20 could directly reduce the basal expression of NLRP3 to impair caspase-1 activation and inhibit the assembling of NLRP3 inflammasome by suppressing the activation of NF-κB, playing a crucial anti-inflammatory role in JIA. A20 and NLRP3 inflammasome may be promising prognostic markers and therapeutic targets in JIA. This review summarized the structure and biological function of A20 and NLRP3 inflammasome and analyzed their roles in the genetic susceptibility and pathogenesis of JIA.
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ObjectiveTo conduct a systematic review of the susceptibility gene polymorphism sites of primary knee osteoarthritis (PKO). MethodsThe literature on genetic susceptibility and gene polymorphisms of PKO were retrieved from PubMed, Web of Science, CNKI, Wanfang Data, and China Biomedical Literature Database from establishment of the library to December, 2020, and systematically reviewed. ResultsA total of 42 papers on the polymorphism sites of human PKO susceptibility genes were included, involving cellular signaling pathways related to PKO pathogenesis, including inflammatory response, receptor signaling pathway, transcription factor signaling pathway, bone-related signaling pathway, etc. Multiple gene polymorphism sites located in inflammatory factor genes, chemokine genes, Toll-like receptor genes, transcription factor genes, obesity-related genes, and bone-related genes. ConclusionInflammatory factor genes and bone-associated allele polymorphisms are likely to be related to PKO susceptibility.
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Objective@#Systematic evaluation of the correlation of HLA-DQB1 and HLA-DRB1 allele polymorphisms with caries, to provide reference for caries prevention and treatment. @*Methods@# Relevant literature published before December 2020 was searched in the Cochrane Library, PubMed, Embase, Web of Science, Scopus, CNKI, Wanfang, VIP, and CBM databases. Meta-analysis was performed using the R4.0.2 software to test for heterogeneity and evaluate the publication bias.@*Results @# In total,10 case-control studies were included with 564 people in the case group and 676 people in the control group. The results of the Meta-analysis show that: ① HLA-DQB1*02 (OR=0.52, 95%CI=0.29-0.93, P < 0.05) and HLA-DRB1*09 (OR=0.34, 95%CI=0.21-0.58, P < 0.05) are protective factors of dental caries; ② HLA-DRB1*13 (OR=2.96, 95%CI=2.03-4.33, P < 0.05) and HLA-DRB1*14 (OR=1.95, 95%CI=1.26-3.02, P < 0.05) alleles are risk factors for the development of dental caries. The results of the subgroup analysis are: HLA-DRB1*07 is a caries susceptibility factor in the Chinese population (OR=0.48, 95% CI=0.24-0.97, P < 0.05), while it is not statistically significant in the Brazilian and Turkish populations; HLA-DRB1*11 is a caries protective factor in the saliva group (OR=2.26, 95% CI=1.46-3.52, P < 0.05). 3.52, P < 0.001), while it is a caries susceptibility factor in the blood group (OR=0.09, 95% CI=0.12-0.34, P < 0.001). @*Conclusion @#HLA-DRB1*13 and HLA-DRB1*14 alleles are caries susceptibility genes, and HLA-DQB1*02 and HLA-DRB1*09 have protective effects on the caries development. HLA-DRB1*07 is a caries susceptibility gene in the Chinese population; HLA-DRB1*11 is a caries protective gene in the saliva group. Due to the limited sample size and quality of the included studies, more high-quality studies will be included later for verification.
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@#Diabetic retinopathy(DR)is a kind of multi-factor mediated diseases, currently accepted DR environment that is caused by chronic high blood glucose metabolic abnormalities caused by, but it is regulated by the genetic factors, is considered to be a classic case of complex diseases, can be attributed to genetic factors, environmental factors and the interaction of the results. Genetic studies on the occurrence and development of DR have achieved some results, but the specific pathogenic genes and their pathogenesis are still not clear. In this study, potential DR susceptibility genes and their polymorphisms have been identified so far, so as to provide reference for further study of DR pathogenic genes and their pathogenesis.
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Sepsis is a clinical syndrome caused by the host reaction disorder induced by infection, which leads to serious organ function damage. Sepsis is a serious disease with high mortality, which is the main reason of death caused by infection. Single nucleotide polymorphisms (SNP) is one of the most common genetic variants in human, and is closely related to the genetic susceptibility, early diagnosis, disease development and prognosis of sepsis. This article makes a review on the relationship between CD14, Toll like receptor (TLR), tumor necrosis factor (TNF), interleukins (IL-1 and IL-6), plasminogen activator inhibitor 1 (PAI-1), angiotensin converting enzyme (ACE) and other gene polymorphisms and genetic susceptibility of sepsis, in order to affect in sepsis on the early prediction, diagnosis, and treatment.
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Brucellosis is a kind of animal epidemic disease that can be transmitted to human beings through skin, mucous membrane, digestive tract, respiratory tract and other ways. In recent years, the incidence of brucellosis has increased. Its pathogenesis is relatively complicated. In addition to bacteria, toxins and other factors, genetic susceptibility has gradually attracted the attention of scholars. In this paper, we summarized the previous reports and reviewed the relationship between interleukin gene polymorphism and susceptibility to brucellosis.
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Tumor calcinosis(TC) has different clinical and biochemical patterns. The existence of chronic injury as well as calcium and phosphorus metabolism disorder has been gradually proved to be the important link in the occurrence of TC. In this paper, the related basic diseases with the pathophysiological mechanism of calcium and phosphorus metabolism disorder were reviewed, and the pathophysiological mechanism of phosphate metabolism disorder in various diseases was summarized.In addition, the phosphate homeostasis genes including GALNT-3, FGF-23 and α-KLOTHO were described. The relevant research results have showed that mutations in any of these three genes will lead to defects in the synthesis or action of FGF-23, which will increase the reabsorption of phosphate by renal tubules, resulting in hyperphosphatemia and severe ectopic calcification of soft tissue.At present, surgical resection is still the main treatment of TC. New technologies such as cinalcet peritoneal dialysis, ultrasound-guided aspiration of TC lesions and local injection of sodium thiosulfate (STS), as well as the successful application of lanthanum carbonate and other drugs, provide alternatives to TC treatment.In this paper, the research literatures on TC at home and abroad in recent years were introduced and the genetic susceptibility genes, related pathogenic factors and the latest treatment progress of TC were reviewed.
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RESUMEN Introducción: la COVID-19 (acrónimo del inglés c oronavirus disease 2019) es una enfermedad infecciosa de reciente descripción, causada por el SARS-CoV-2, sin tratamiento efectivo. La identificación de variantes genéticas que intervienen en la respuesta a la COVID-19; así como la posibilidad de trasmisión materno-fetal del SARS-CoV-2 no solo permitirán ampliar los conocimientos sobre su fisiopatología; sino además estratificar los grupos de la población, y según su riesgo, implementar medidas preventivas y tratamientos personalizados, incluida la prioridad en el uso de vacunas. Objetivo: describir aspectos relacionados con la susceptibilidad genética y defectos congénitos en la COVID-19. Material y Métodos: se realizó una investigación tipo revisión bibliográfica; para identificar los documentos que se revisarían se consultó la base bibliográfica PubMed/Medline, incluyendo los trabajos del 2019 y 2020. Se incluyó publicaciones recomendadas por expertos, preferiblemente publicados en los últimos 10 años; luego de una valoración cualitativa, se realizó una síntesis. Desarrollo: están descritas mutaciones de los genes: ACE2, ACE1, TMPRSS2, TLR7, así como haplotipos HLA asociadas a la susceptibilidad genética a la COVID-19. Variantes de los genes: SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 y XCR1; así como de los que codifican para el receptor de la Vitamina D y las citoquinas pro inflamatorias (como las IL-1, IL-6, IL-12, IFN-γ, y TNT-α), pudieran también estar relacionadas con un incremento de la susceptibilidad al SARS-CoV-2. Ante la posibilidad de trasmisión vertical de la COVID-19 y su posible papel teratogénico, las embarazadas constituyen un grupo de riesgo. Conclusión: variantes genéticas humanas son factores de susceptibilidad genética al virus SARS-CoV-2, que puede ser causa de defectos congénitos(AU)
ABSTRACT Introduction: COVID-19 (acronym for Coronavirus Disease 2019) is a recently described infectious disease caused by SARS-CoV-2, without effective treatment. Identification of genetic variants involved in the response to COVID-19 as well as the possibility of maternal-fetal transmission of SARS-CoV-2 will not only allow us to expand our knowledge of the pathophysiology of COVID-19, but also stratify population groups according to their risks in order to implement preventive measures and personalized treatments, including the priority in the use of vaccines. Objective: To describe aspects related to congenital defects and genetic susceptibility to the SARS-CoV-2 virus. Material and Methods: A bibliographic review was carried out. Medline and PubMed bibliographic databases were searched. Studies published between 2019 and 2020 were included as well the ones recommended by experts, preferably published within the last 10 years. After qualitative evaluation, synthesis was made. Development: Mutations in ACE2, ACE1, TMPRSS2, TLR7 genes, as well as HLA haplotypes associated with genetic susceptibility to COVID-19 are described. Variants in the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1 and in those codifying vitamin D receptor and proinflammatory cytokines (IL-1, IL-6, IL-12, IFN-γ, and TNF-α) could be related to an increased susceptibility to SARS-CoV-2. Due to the risk of vertical transmission of COVID-19 and its possible teratogenic effect, pregnant women are included in the risk group. Conclusion: Human genetic variants are factors of genetic susceptibility to the SARS-CoV-2 virus which may cause congenital defects(AU)
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Humans , Coronavirus Infections/geneticsABSTRACT
@#Environmental factors are important risk factor for lung cancer. Smokers are 20 times more likely to develop lung cancer than non-smokers. However, less than 20% of smokers develop lung cancer. In recent years, many studies have shown genetic polymor‐phism plays an important role in the development of lung cancer, mainly involving single nucleotide polymorphisms and rare highexogenous mutations. The in-depth research of the gene polymorphism will be beneficial to the screen of susceptible genes in lung cancer and genetically high-risk population, providing genetic counseling and evidence for clinically precise diagnosis and treatment. This article mainly summarizes the contents regarding genetic susceptibility of lung cancer and high-risk population screening, early diagnosis of lung cancer as well as precise medication of advanced lung cancer.
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@#Non-arteritic anterior ischemic optic neuropathy is an acute optic nerve disease that seriously impairs the visual function of middle-aged and elderly people. It is generally believed to be caused by ischemia of the short ciliary artery supplying the optic disc plate area and the posterior area of the sieve plate. The disease is associated with a variety of factors, such as diabetes that affects the systemic microcirculation, hypertension and respiratory sleep apnea syndrome that has been widely studied recently, and so on. Moreover, it was also found that genetic susceptibility, drugs, surgery and ocular diseases were all associated with the occurrence and development of the NAION. In this paper, the latest researches on these factors are reviewed.
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Resumen Los carcinógenos ambientales y el virus del papiloma humano (VPH) son los principales responsables del cáncer bucal. Los factores de susceptibilidad en el genoma humano desempeñan un papel modulador del riesgo, sin embargo, no todos los individuos expuestos a los carcinógenos padecen cáncer. El objetivo de la presente revisión es describir los principales factores de susceptibilidad genética para cáncer bucal en individuos con infección por VPH. Se realizó una búsqueda sistemática en tres bases de datos en inglés; solo siete artículos cumplieron con los criterios de selección. Se registraron polimorfismos genéticos en tres categorías relacionados con el VPH y que participan en la oncogénesis. Se identificaron tres artículos relativos a la desregulación de los mecanismos de control del ciclo celular, uno relativo a mutaciones en la vía de la apoptosis y tres a polimorfismos en genes de respuesta inflamatoria e inmune. La asociación entre polimorfismos para el desarrollo de cáncer bucal y VPH es evidente, aunque continúa en estudio ya que no siempre el patrón de oncogénesis de las neoplasias bucales está relacionado con el VPH, sino con otros factores ambientales o epigenéticos.
Abstract Environmental carcinogens and human papillomavirus (HPV) are the main responsible factors for oral cancer. Susceptibility factors in the human genome play a risk-modulating role; however not all individuals exposed to these carcinogens suffer from cancer. The purpose of the present review is to describe the main factors of genetic susceptibility to oral cancer due to HPV infection. A systematic search was carried out in three databases in English, with only 7 articles meeting the selection criteria. Genetic polymorphisms are shown in three categories, which are related to HPV and participate in oncogenesis. Three articles related to deregulation of cell cycle control mechanisms were identified, as well as one referring to mutations in the apoptosis pathway and three about polymorphisms in inflammatory and immune response genes. The association of polymorphisms for the development of oral cancer by HPV is evident, although it remains under study. Oral neoplasms oncogenesis pattern is not always associated with HPV, but with other environmental or epigenetic factors.
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Humans , Mouth Neoplasms/epidemiology , Genetic Predisposition to Disease , Papillomavirus Infections/complications , Papillomaviridae/isolation & purification , Polymorphism, Genetic , Mouth Neoplasms/genetics , Mouth Neoplasms/virology , Risk Factors , Epigenesis, GeneticABSTRACT
Abstract Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in developed countries. Although cigarette smoking is the major risk factor, only 10-20% of smokers develop COPD. The extent of cigarette smoking (pack-years and smoking duration) accounts for only 15% of the variation in lung function, indicating that differences in susceptibility to COPD must exist. We provide an overview of the complexity of nicotine addiction and COPD, with special attention to the involvement of genetic factors. The following aspects are discussed in the present article: (1) epidemiology in Mexico and (2) a review of the published literature on genetic association studies using the National Center for Biotechnology Information database of the United States as a search tool. COPD is unique among complex genetic diseases where an environmental risk factor is known and the level of exposure can be documented with some precision. The high morbidity and mortality associated with COPD and its chronic and progressive nature has prompted the use of molecular genetic studies to identify susceptibility factors for the disease. Biomedical research has a remarkable set of tools to aid in the discovery of genes and polymorphisms. We present a review of the most relevant genetic associations in nicotine addiction and COPD.
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Humans , Tobacco Use Disorder/genetics , Genetic Predisposition to Disease , Pulmonary Disease, Chronic Obstructive/genetics , Tobacco Use Disorder/complications , Tobacco Use Disorder/epidemiology , Smoking/adverse effects , Smoking/genetics , Smoking/epidemiology , Risk Factors , Disease Progression , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Mexico/epidemiology , Nicotine/administration & dosage , Nicotine/adverse effectsABSTRACT
Background: The case–control study aimed to investigate the association between the −31G>C polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer (CRC) in a Southern Chinese population. Materials and Methods: The study was carried out on 711 healthy controls and 702 CRC cases of a Southern Chinese population. Survivin gene −31G>C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The association between CRC risk and −31G>C genetic polymorphism was estimated using an unconditional logistic regression model. Results: The number of CC genotype carried in CRC patients was much higher than those of controls (P < 0.001). Compared with CC genotypes, GC, GG genotypes and −31G wild-type genotypes (i.e., GC + GG) had a significantly decreased risk of CRC (P < 0.001). In addition, survivin −31G wild-type genotypes were not associated with decreased risk of sporadic CRC patients with body mass index (BMI) ≥28.0 kg/m2, family cancer history, and premenopausal. Conclusion: Survivin −31G>C polymorphism is associated with sporadic CRC risk in the Southern Chinese population. The −31G wild-type genotypes and GC, GG genotypes are the independent protective factors against sporadic CRC excluding those with a BMI ≥28.0 kg/m2, family cancer history, and premenopausal
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Introducción. El cáncer colorrectal es una carga para la salud pública en Colombia y el mundo. Estudios de asociación genética han identificado regiones cromosómicas asociadas a esta enfermedad, mostrando riesgo variable entre poblaciones, debido a la historia demográfica y la ancestría genética. Objetivo. Estudiar el riesgo que aportan 20 marcadores al cáncer colorrectal en Colombia, empleando 955 casos y 972 controles del consorcio CHIBCHA, analizando conjuntamente el efecto de la ancestría genética global y local. Metodología. Las muestras se genotipificaron usando microarreglos Axyom Affymetrix LAT y CUSTOME, para obtener los genotipos genómicos globales, incluyendo 20 SNPs de riesgo. Los análisis estadísticos se realizaron en PLINK (asociaciones), ADMIXTURE (ancestría global), Elai (ancestría local) y R (modelos logísticos). Resultados. Once regiones cromosómicas resultaron asociadas presentando ORs entre 1.14 y 1.41 (p<0.05): 18q21.1, 19q13.11, 10p14, 14q.2.2, 20p12.3, 8q23.3, 6p21.2, 15q13.3 y 8q24.21. Una mayor ancestría europea se asoció con el riesgo a nivel global (OR=3.016, IC 95%:1.162-7.894, p=0.00325), y a nivel cromosómico local se detectaron las regiones 6q23.2 (ORajustado=1.378, IC95%: 1.202-1.580, Pajustado=4.2e-6) y 4p13 (ORajustado=1.301, IC95%:1.137-1.489; Pajustado=0.00013). Conclusiones. La ancestría podría considerarse un factor en la explicación de la susceptibilidad en Colombia, indicando que la mezcla genética de origen amerindio y europeo, influye en la estructura poblacional y explicaría las diferencias en la incidencia del CCR entre poblaciones latinas y europeas.
Introduction: Colorectal cancer is a public health burden in the world and Colombia. Recent genome wide association studies have identified chromosomal regions associated with the disease, depicting variable risk between populations, owing to the demographic history and genetic ancestry. Objective: We aimed to study the colorectal cancer risk in Colombia provided for 20 genetic markers, by using 955 cases and 972 controls from the CHIBCHA consortium, in the context of global and local genetic ancestry. Methodology: The samples were genotyped using Axyom Affymetrix LAT and CUSTOME array in order to obtain the global genome genotypes including 20 risk SNPs. Statistical analysis was performed in PLINK (associations), ADMIXTURE (global ancestry), Elai (local ancestry) and R language (logistic models). Results: Eleven chromosomal regions were associated with ORs ranging between 1.14-1.41 (p<0.05): 18q21.1, 19q13.11, 10p14, 14q.2.2, 20p12.3, 8q23.3, 6p21.2, 15q13.3 y 8q24.21. On average, a higher global European ancestry was associated with colorectal cancer risk (OR=3.016, IC 95%:1.162-7.894, p=0.00325). At the local chromosomal level two regions presented a significant increment of European ancestry 6q23.2 (OR adjusted=1.378, CI95%: 1.202-1.580, p adjusted =4.2e-6) and 4p13 (OR adjusted =1.301, CI95%:1.137-1.489; p adjusted =0.00013). Conclusions: Genetic ancestry can be considered as a relevant factor for the colorectal cancer susceptibility in Colombia. Both Native American and European ancestry are accounting for the most part of population structure in the sample we studied, which could explain the differences for the colorectal cancer incidence between Latin American and European populations.