Gene/Protein Disease Symptom Drug Enzyme Compound
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 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growing number of human cancers is the main reason for the search for new effective treatment strategies. The molecular basis for cancer transformation has to be elucidated in order to improve cancer treatment. It is stated that HNSCCs make up at least 5% of all registered malignant tumors in Poland. Exogenous factors influence HNSCC etiology. The prevalence of HNSCC is increased by several carcinogens, including tobacco smoke, life style, and others, such as oncogenous viral infections. It is more often emphasized that endogenous agents can also increase the risk of HNSCC development, especially genetic factors. The most recently characterized genetic factors for head and neck cancer are mutations in xenobiotic metabolism enzyme genes (GSTM1, GSTT1, GSTP1), suppressors mutations (TP53, RB1, BRCA1, ATM), polymorphisms of DNA repair genes (OGG1, XRCC1, XPD, RAD51), and mutations in mitochondrial DNA. It has been observed that single-gene polymorphisms could affect treatment, whereas the coincidence of other gene mutations may increase the risk of human head and neck cancer development.
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PMID:[Genetic predeterminations of head and neck cancer]. 1883 34

Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.
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PMID:Molecular Links between Alcohol and Tobacco Induced DNA Damage, Gene Polymorphisms and Patho-physiological Consequences: A Systematic Review of Hepatic Carcinogenesis. 2616 95

Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01-8.83; OR = 2.04, 95% CI = 0.99-4.27; OR = 1.74, 95% CI = 1.00-3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated.
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PMID:Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan. 2629 53

Clinical resistance to chemotherapy is one of the major problems in breast cancer treatment. In this study we analyzed possible impact of 22 polymorphic variants on the treatment response in 324 breast cancer patients. Selected genes were involved in FAC chemotherapy drugs transport (ABCB1, ABCC2, ABCG2, SLC22A16), metabolism (CYP1B1, CYP2C19, GSTT1, GSTM1, GSTP1, TYMS, MTHFR, DPYD), drug-induced damage repair (ERCC1, ERCC2, XRCC1) and involved in regulation of DNA damage response and cell cycle control (ATM, TP53).Apart from preexisting metastases three polymorphic variants were independent prognostic high risk factors of lack of response to FAC chemotherapy. Our results showed that the response to treatment depended of the variability in genes engaged in drugs' transport (ABCC2 c.-24C>T, ABCB1 p.Ser893Ala/Thr) and in DNA repair machinery (ERCC2 p.Lys751Gln). Furthermore, the growing number of high-risk genotypes was reflected in gradual increase in risk of the non-responsiveness to treatment- from OR 2.68 for presence of two genotypes to OR 9.93 for carriers of all three negative genotypes in the group of all patients. Similar gene-dosage effect was observed in the subgroup of TNBCs. Also, TFFS significantly shortened with the increasing number of high-risk genotypes, with median of 54.4 months for carriers of one variant, to 51.5 and 34.9 months for the carriers of two and three genotypes, respectively.Our results demonstrate that results of cancer treatment are the effect of many clinical and genetic factors. It seems that multifactorial polymorphic models could be a potentially useful tool in personalization of cancer therapies. The novelty in our model is the over representation of triple negative breast cancer (TNBC) patients among the carriers of all unfavorable polymorphic variants. This finding contributes to the elucidation of the mechanisms of drug resistance in this subgroup of breast cancer patients.
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PMID:Genetic polymorphisms and response to 5-fluorouracil, doxorubicin and cyclophosphamide chemotherapy in breast cancer patients. 2752 55

Oral cancer etiology is complex and controlled by multi-factorial events including genetic events. Candidate gene studies, genome-wide association studies, and next-generation sequencing identified various chromosomal loci to be associated with oral cancer. There is no available review that could give us the comprehensive picture of genetic loci identified to be associated with oral cancer by candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based approaches. A systematic literature search was performed in the PubMed database to identify the loci associated with oral cancer by exclusive candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based study approaches. The information of loci associated with oral cancer is made online through the resource "ORNATE." Next, screening of the loci validated by candidate gene studies and next-generation sequencing approach or by two independent studies within candidate gene studies or next-generation sequencing approaches were performed. A total of 264 loci were identified to be associated with oral cancer by candidate gene studies, genome-wide association studies, and next-generation sequencing approaches. In total, 28 loci, that is, 14q32.33 (AKT1), 5q22.2 (APC), 11q22.3 (ATM), 2q33.1 (CASP8), 11q13.3 (CCND1), 16q22.1 (CDH1), 9p21.3 (CDKN2A), 1q31.1 (COX-2), 7p11.2 (EGFR), 22q13.2 (EP300), 4q35.2 (FAT1), 4q31.3 (FBXW7), 4p16.3 (FGFR3), 1p13.3 (GSTM1-GSTT1), 11q13.2 (GSTP1), 11p15.5 (H-RAS), 3p25.3 (hOGG1), 1q32.1 (IL-10), 4q13.3 (IL-8), 12p12.1 (KRAS), 12q15 (MDM2), 12q13.12 (MLL2), 9q34.3 (NOTCH1), 17p13.1 (p53), 3q26.32 (PIK3CA), 10q23.31 (PTEN), 13q14.2 (RB1), and 5q14.2 (XRCC4), were validated to be associated with oral cancer. "ORNATE" gives a snapshot of genetic loci associated with oral cancer. All 28 loci were validated to be linked to oral cancer for which further fine-mapping followed by gene-by-gene and gene-environment interaction studies is needed to confirm their involvement in modifying oral cancer.
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PMID:Signature of genetic associations in oral cancer. 2903 25

The differences in patients' response to the same medication, toxicity included, are one of the major problems in breast cancer treatment. Chemotherapy toxicity makes a significant clinical problem due to decreased quality of life, prolongation of treatment and reinforcement of negative emotions associated with therapy. In this study we evaluated the genetic and clinical risk factors of FAC chemotherapy-related toxicities in the group of 324 breast cancer patients. Selected genes and their polymorphisms were involved in FAC drugs transport (ABCB1, ABCC2, ABCG2,SLC22A16), metabolism (ALDH3A1, CBR1, CYP1B1, CYP2C19, DPYD, GSTM1, GSTP1, GSTT1, MTHFR,TYMS), DNA damage recognition, repair and cell cycle control (ATM, ERCC1, ERCC2, TP53, XRCC1). The multifactorial risk models that combine genetic risk modifiers and clinical characteristics were constructed for 12 toxic symptoms. The majority of toxicities was dependent on the modifications in components of more than one pathway of FAC drugs, while the impact level of clinical factors was comparable to the genetic ones. For the carriers of multiple high risk factors the chance of developing given symptom was significantly elevated which proved the factor-dosage effect. We found the strongest associations between concurrent presence of clinical factors - overall and recurrent anemia, nephrotoxicity and early nausea and genetic polymorphisms in genes responsible for DNA repair, drugs metabolism and transport pathways. These results indicate the possibility of selection of the patients with expected high tolerance to FAC treatment and consequently with high chance of chemotherapy completion without the dose reduction, treatment delays and decline in the quality of life.
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PMID:Pharmacogenetics of toxicity of 5-fluorouracil, doxorubicin and cyclophosphamide chemotherapy in breast cancer patients. 2950 78