Impact of Gene–Environment Interactions on Cancer Development

Several epidemiological and experimental studies have demonstrated that many human diseases are not only caused by specific genetic and environmental factors but also by gene–environment interactions. Although it has been widely reported that genetic polymorphisms play a critical role in human susceptibility to cancer and other chronic disease conditions, many single nucleotide polymorphisms (SNPs) are caused by somatic mutations resulting from human exposure to environmental stressors. Scientific evidence suggests that the etiology of many chronic illnesses is caused by the joint effect between genetics and the environment. Research has also pointed out that the interactions of environmental factors with specific allelic variants highly modulate the susceptibility to diseases. Hence, many scientific discoveries on gene–environment interactions have elucidated the impact of their combined effect on the incidence and/or prevalence rate of human diseases. In this review, we provide an overview of the nature of gene–environment interactions, and discuss their role in human cancers, with special emphases on lung, colorectal, bladder, breast, ovarian, and prostate cancers.

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Mechanisms and modifiers of methylmercury-induced neurotoxicity

Toxicology Research ◽

10.1039/c2tx20010d ◽

2012 ◽

Vol 1 (1) ◽

pp. 32-38 ◽

Cited By ~ 23

Author(s):

Stephanie J. B. Fretham ◽

Samuel Caito ◽

Ebany J. Martinez-Finley ◽

Michael Aschner

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Environmental Factors ◽

Genetic Polymorphisms ◽

Experimental Studies ◽

Mehg Exposure ◽

Complete Understanding ◽

Cellular Processes ◽

Gene Environment ◽

Genetic And Environmental Factors

Abstract The neurotoxic consequences of methylmercury (MeHg) exposure have long been known, however a complete understanding of the mechanisms underlying this toxicity is elusive. Recent epidemiological and experimental studies have provided mechanistic insights into the contribution of genetic and environmental factors that interact with MeHg to modify toxicity. This review will outline cellular processes directly and indirectly affected by MeHg, including oxidative stress, cellular signaling and gene expression, and discuss epigenetic modifications, genetic polymorphisms and gene–environment interactions capable of modifying MeHg neurotoxicity.

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Association Study among Comethylation Modules, Genetic Polymorphisms and Clinical Features in Mexican Teenagers with Eating Disorders: Preliminary Results

Nutrients ◽

10.3390/nu13093210 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3210

Author(s):

Germán Alberto Nolasco-Rosales ◽

José Jaime Martínez-Magaña ◽

Isela Esther Juárez-Rojop ◽

Thelma Beatriz González-Castro ◽

Carlos Alfonso Tovilla-Zarate ◽

...

Keyword(s):

Dna Methylation ◽

Eating Disorders ◽

Environmental Factors ◽

Clinical Features ◽

Eating Behaviors ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Gene Environment ◽

Gene Correlation ◽

Genetic And Environmental Factors

Eating disorders are psychiatric disorders characterized by disturbed eating behaviors. They have a complex etiology in which genetic and environmental factors interact. Analyzing gene-environment interactions could help us to identify the mechanisms involved in the etiology of such conditions. For example, comethylation module analysis could detect the small effects of epigenetic interactions, reflecting the influence of environmental factors. We used MethylationEPIC and Psycharray microarrays to determine DNA methylation levels and genotype from 63 teenagers with eating disorders. We identified 11 comethylation modules in WGCNA (Weighted Gene Correlation Network Analysis) and correlated them with single nucleotide polymorphisms (SNP) and clinical features in our subjects. Two comethylation modules correlated with clinical features (BMI and height) in our sample and with SNPs associated with these phenotypes. One of these comethylation modules (yellow) correlated with BMI and rs10494217 polymorphism (associated with waist-hip ratio). Another module (black) was correlated with height, rs9349206, rs11761528, and rs17726787 SNPs; these polymorphisms were associated with height in previous GWAS. Our data suggest that genetic variations could alter epigenetics, and that these perturbations could be reflected as variations in clinical features.

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Gene-Environment Interactions in Progressive Supranuclear Palsy

Frontiers in Neurology ◽

10.3389/fneur.2021.664796 ◽

2021 ◽

Vol 12 ◽

Author(s):

Irene Litvan ◽

James A. Proudfoot ◽

Eden R. Martin ◽

David Standaert ◽

David Riley ◽

...

Keyword(s):

Environmental Factors ◽

Progressive Supranuclear Palsy ◽

Symptom Onset ◽

Nucleotide Polymorphisms ◽

Agricultural Risk ◽

Single Nucleotide ◽

Gene Environment ◽

Minor Alleles ◽

Genetic And Environmental Factors ◽

Potential Interactions

Several genetic and environmental factors have been reported in progressive supranuclear palsy (PSP), although none were identified as a definitive cause. We aimed to explore potential gene-environment interactions in PSP. Two hundred and ninety two PSP cases and 292 controls matched for age, sex, and race from the ENGENE-PSP were analyzed to determine the association between PSP and minor alleles of 5 single nucleotide polymorphisms (SNPs) in 4 genes (MAPT, MOBP, EIF2AK3, and STX6), which were previously associated with PSP risk. Interactions between these SNPs and environmental factors, including previously reported occupational and agricultural risk factors for PSP, were assessed for PSP odds and age of symptom onset. Minor alleles of MAPTrs242557 and EIF2AK3rs7571971 were individually associated with increased odds; MAPTrs8070723 minor alleles were associated with lower PSP odds. There were several gene-environment interactions for PSP odds and age of symptom onset, however, they did not remain significant after FDR-correction. Larger scale studies are required to determine potential interactions.

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Impacts of Environmental Factors on Head and Neck Cancer Pathogenesis and Progression

Cells ◽

10.3390/cells10020389 ◽

2021 ◽

Vol 10 (2) ◽

pp. 389

Author(s):

Marisol Miranda-Galvis ◽

Reid Loveless ◽

Luiz Paulo Kowalski ◽

Yong Teng

Keyword(s):

Head And Neck Cancer ◽

Environmental Factors ◽

Head And Neck ◽

Neck Cancer ◽

Molecular Mechanisms ◽

Metastatic Cancer ◽

Environmental Drivers ◽

Cancer Pathogenesis ◽

Gene Environment ◽

The Impact

Epidemiological and clinical studies over the past two decades have provided strong evidence that genetic elements interacting with environmental components can individually and collectively influence one’s susceptibility to cancer. In addition to tumorigenic properties, numerous environmental factors, such as nutrition, chemical carcinogens, and tobacco/alcohol consumption, possess pro-invasive and pro-metastatic cancer features. In contrast to traditional cancer treatment, modern therapeutics not only take into account an individual’s genetic makeup but also consider gene–environment interactions. The current review sharpens the focus by elaborating on the impact that environmental factors have on the pathogenesis and progression of head and neck cancer and the underlying molecular mechanisms involved. Recent advances, challenges, and future perspectives in this area of research are also discussed. Inhibiting key environmental drivers of tumor progression should yield survival benefits for patients at any stage of head and neck cancer.

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Supplementation and therapeutic use of vitamin D in patients with multiple sclerosis: Consensus of the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130252 ◽

2014 ◽

Vol 72 (2) ◽

pp. 152-156 ◽

Cited By ~ 5

Author(s):

Doralina Guimarães Brum ◽

Elizabeth Regina Comini-Frota ◽

Claúdia Cristina F. Vasconcelos ◽

Elza Dias-Tosta

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Vitamin D ◽

Environmental Factors ◽

Scientific Evidence ◽

Hypovitaminosis D ◽

Central Nervous System Disease ◽

Keywords Multiple Sclerosis ◽

System Disease ◽

Genetic And Environmental Factors

Multiple sclerosis (MS) is an inflammatory, autoimmune, demyelinating, and degenerative central nervous system disease. Even though the etiology of MS has not yet been fully elucidated, there is evidence that genetic and environmental factors interact to cause the disease. Among the main environmental factors studied, those more likely associated with MS include certain viruses, smoking, and hypovitaminosis D. This review aimed to determine whether there is evidence to recommend the use of vitamin D as monotherapy or as adjunct therapy in patients with MS. We searched PUBMED, EMBASE, COCHRANNE, and LILACS databases for studies published until September 9 th , 2013, using the keywords “multiple sclerosis”, “vitamin D”, and “clinical trial”. There is no scientific evidence up to the production of this consensus for the use of vitamin D as monotherapy for MS in clinical practice.

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Gene–gene and gene-environment interactions on cord blood total IgE in Chinese Han children

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00571-0 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Li Hua ◽

Quanhua Liu ◽

Jing Li ◽

Xianbo Zuo ◽

Qian Chen ◽

...

Keyword(s):

Environmental Factors ◽

Cord Blood ◽

Synergistic Effects ◽

Gene Interaction ◽

Independent Effect ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Gene Environment Interaction ◽

Gene Environment

Abstract Background IL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population. Methods 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods. Results A four-way gene–gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10–4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10–3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10–2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10–2). Conclusions Gene–gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.

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Gene–environment interplay in the etiology of psychosis

Psychological Medicine ◽

10.1017/s003329171700383x ◽

2018 ◽

Vol 48 (12) ◽

pp. 1925-1936 ◽

Cited By ~ 26

Author(s):

Alyson Zwicker ◽

Eileen M. Denovan-Wright ◽

Rudolf Uher

Keyword(s):

Environmental Factors ◽

Genetic Risk ◽

Environmental Exposures ◽

Response To Treatment ◽

Human Potential ◽

Specific Gene ◽

Environment Interaction ◽

Gene Environment ◽

Increased Risk ◽

The Impact

AbstractSchizophrenia and other types of psychosis incur suffering, high health care costs and loss of human potential, due to the combination of early onset and poor response to treatment. Our ability to prevent or cure psychosis depends on knowledge of causal mechanisms. Molecular genetic studies show that thousands of common and rare variants contribute to the genetic risk for psychosis. Epidemiological studies have identified many environmental factors associated with increased risk of psychosis. However, no single genetic or environmental factor is sufficient to cause psychosis on its own. The risk of developing psychosis increases with the accumulation of many genetic risk variants and exposures to multiple adverse environmental factors. Additionally, the impact of environmental exposures likely depends on genetic factors, through gene–environment interactions. Only a few specific gene–environment combinations that lead to increased risk of psychosis have been identified to date. An example of replicable gene–environment interaction is a common polymorphism in theAKT1gene that makes its carriers sensitive to developing psychosis with regular cannabis use. A synthesis of results from twin studies, molecular genetics, and epidemiological research outlines the many genetic and environmental factors contributing to psychosis. The interplay between these factors needs to be considered to draw a complete picture of etiology. To reach a more complete explanation of psychosis that can inform preventive strategies, future research should focus on longitudinal assessments of multiple environmental exposures within large, genotyped cohorts beginning early in life.

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Study of rs12532, rs8670 Polymorphism of Msh Homeobox 1 (MSX1), rs61754301, rs4904155 Polymorphism of Paired Box Gene 9 (PAX9), and rs2240308 Polymorphism of Axis Inhibitor Protein 2 (AXIN2) Genes in Nonsyndromic Hypodontia

BioMed Research International ◽

10.1155/2019/2183720 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Krisztina Mártha ◽

Bernadette Kerekes Máthé ◽

Valeriu George Moldovan ◽

Claudia Bănescu

Keyword(s):

Environmental Factors ◽

Genetic Background ◽

Orthodontic Treatment ◽

Statistical Significance ◽

Nucleotide Polymorphisms ◽

Inhibitor Protein ◽

Single Nucleotide ◽

Variant Genotype ◽

Genetic And Environmental Factors ◽

Age And Sex

The etiology of hypodontia is complex, in which both genetic and environmental factors can be related. The main objective of our study was to contribute to elucidating the genetic background of nonsyndromic hypodontia (NSH). In this order, we selected 97 NSH subjects (70 females and 27 males) from patients referred to orthodontic treatment, and we matched to each NSH subject a control by age and sex. DNA was obtained from epithelial cells from the oral mucosa. Genotyping of the PAX9 (rs4904155 and rs61754301), MSX1 (rs8670 and rs12532), and AXIN2 (rs2240308) SNPs was performed by using TaqMan SNP Genotyping Assays on a real-time PCR system. Single-nucleotide polymorphisms (SNPs) were studied for the whole NSH group and for frontal and lateral agenesis NSH subjects separately. Our results showed that the variant genotype (p=0.0008, OR = 2.9, 95% CI = 1.58–5.3) and variant T allele (p=0.0002, OR = 2.65, 95% CI = 1.6–4.39) of the MSX1 rs8670 SNP increased the risk of hypodontia in the studied population when the whole NSH group was compared with controls. The variant genotype of the MSX1 rs8670 SNP was the most frequent in frontal agenesis; meanwhile in the lateral agenesis NSH group, the AXIN2 rs2240308 SNP showed a higher frequency of the variant genotype, with a trend towards statistical significance. In conclusion, the results of the present study showed that the variant genotype and variant T allele of the MSX1 rs8670 SNP increased the risk of hypodontia in the studied population. The presence of the variant A allele of AXIN2 rs2240308 is associated with frontal agenesis but not with lateral agenesis.

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How to identify gene–environment interactions in a multifactorial disease: CHD as an example

Proceedings of The Nutrition Society ◽

10.1079/pns2003311 ◽

2004 ◽

Vol 63 (1) ◽

pp. 5-10 ◽

Cited By ~ 25

Author(s):

Philippa J. Talmud

Keyword(s):

Environmental Factors ◽

Context Dependency ◽

Single Mutation ◽

Small Contribution ◽

Multifactorial Disease ◽

Risk Environment ◽

Chd Risk ◽

Gene Environment ◽

E4 Allele ◽

The Impact

CHD is a multifactorial disease, caused by both genetic and environmental factors. The inherited 'defective' genes will vary from individual to individual, and any single mutation is likely to be making only a small contribution to risk. The context dependency, i.e. the importance of environmental factors in influencing genetic risk, is now becoming evident. Thus, a mutation may have a modest effect on risk in individuals who maintain a low environmental risk, but a major effect in a high-risk environment. Methods of analysing gene–environment interactions on CHD risk will be discussed and illustrated with several examples. APOE has three common alleles, ɛ2, ɛ3 and ɛ4. The ɛ4 allele has consistently been associated with CHD risk, which has been confirmed by meta-analysis. However, when the effect of genotype on risk was considered in smokers and non-smokers separately, risk in non-smokers was similar in all APOE genotypes. By comparison, in the smokers, ɛ3 homozygotes, as expected, had an approximately 2-fold higher risk, while for ɛ4 carriers there was a significantly greater than additive effect of genotype and smoking on risk (P ≫0.007). Thus, the impact of the ɛ4 allele on CHD risk appears to be confined to current smokers, an effect that has been confirmed in several studies. Another example is the interaction between the alcohol dehydrogenase 3 gene variant and alcohol consumption on CHD risk (P ≫0.001), showing the context dependency of the effect. Thus, the importance of considering environmental factors as potential genotype-risk modifiers has major public health implications.

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Can Hypoxic Conditioning Improve Bone Metabolism? A Systematic Review

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16101799 ◽

2019 ◽

Vol 16 (10) ◽

pp. 1799 ◽

Cited By ~ 7

Author(s):

Marta Camacho-Cardenosa ◽

Alba Camacho-Cardenosa ◽

Rafael Timón ◽

Guillermo Olcina ◽

Pablo Tomas-Carus ◽

...

Keyword(s):

Bone Metabolism ◽

Critical Role ◽

Hypoxia Inducible Factor ◽

Experimental Studies ◽

Hormonal Responses ◽

Hypoxia Exposure ◽

Ambient Oxygen ◽

The Impact

Among other functions, hypoxia-inducible factor plays a critical role in bone–vascular coupling and bone formation. Studies have suggested that hypoxic conditioning could be a potential nonpharmacological strategy for treating skeletal diseases. However, there is no clear consensus regarding the bone metabolism response to hypoxia. Therefore, this review aims to examine the impact of different modes of hypoxia conditioning on bone metabolism. The PubMed and Web of Science databases were searched for experimental studies written in English that investigated the effects of modification of ambient oxygen on bone remodelling parameters of healthy organisms. Thirty-nine studies analysed the effect of sustained or cyclic hypoxia exposure on genetic and protein expression and mineralisation capacity of different cell models; three studies carried out in animal models implemented sustained or cyclic hypoxia; ten studies examined the effect of sustained, intermittent or cyclic hypoxia on bone health and hormonal responses in humans. Different modes of hypoxic conditioning may have different impacts on bone metabolism both in vivo and in vitro. Additional research is necessary to establish the optimal cyclical dose of oxygen concentration and exposure time.

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