Individual Genetic Polymorphisms Research Articles

Mediterranean diet: Fighting breast cancer naturally: A review.

The effects and mechanisms of the Mediterranean diet (MD) on the incidence, recurrence, and prevention of breast cancer (BC) have been extensively investigated since the 1990s. Recent years have witnessed significant advancements in understanding the relationship between the components of the MD and BC, particularly in terms of their role and adherence. This comprehensive review focuses on several key aspects: the influence of the adherence of MD in cohort studies conducted across different regions on BC, the effects and mechanisms of individual component or main components as well as the supplementation of vitamins, drugs, exercise, and other factors of MD on BC; the variations in the impact of the MD on premenopausal and postmenopausal women, as well as different types in BC cases; the possible mechanisms underlying the development, recurrence, and prevention of BC in relation to the MD; and the interaction effects of individual genetic polymorphisms with the MD. Based on current research findings, this review highlights the key issues and identifies future research directions in investigating the relationship between the MD and BC. Furthermore, it suggests that healthy women of various ages and BC patients should adhere to MD in order to prevent BC or improve the prognosis.

Novel progressive deep learning algorithm for uncovering multiple single nucleotide polymorphism interactions to predict paclitaxel clearance in patients with nonsmall cell lung cancer.

The rate at which the anticancer drug paclitaxel is cleared from the body markedly impacts its dosage and chemotherapy effectiveness. Importantly, paclitaxel clearance varies among individuals, primarily because of genetic polymorphisms. This metabolic variability arises from a nonlinear process that is influenced by multiple single nucleotide polymorphisms (SNPs). Conventional bioinformatics methods struggle to accurately analyze this complex process and, currently, there is no established efficient algorithm for investigating SNP interactions. We developed a novel machine-learning approach called GEP-CSIs data mining algorithm. This algorithm, an advanced version of GEP, uses linear algebra computations to handle discrete variables. The GEP-CSI algorithm calculates a fitness function score based on paclitaxel clearance data and genetic polymorphisms in patients with nonsmall cell lung cancer. The data were divided into a primary set and a validation set for the analysis. We identified and validated 1184 three-SNP combinations that had the highest fitness function values. Notably, SERPINA1, ATF3 and EGF were found to indirectly influence paclitaxel clearance by coordinating the activity of genes previously reported to be significant in paclitaxel clearance. Particularly intriguing was the discovery of a combination of three SNPs in genes FLT1, EGF and MUC16. These SNPs-related proteins were confirmed to interact with each other in the protein-protein interaction network, which formed the basis for further exploration of their functional roles and mechanisms. We successfully developed an effective deep-learning algorithm tailored for the nuanced mining of SNP interactions, leveraging data on paclitaxel clearance and individual genetic polymorphisms.

The Effect of Selected Polymorphisms of the ACTN3, ACE, HIF1A and PPARA Genes on the Immediate Supercompensation Training Effect of Elite Slovak Endurance Runners and Football Players.

We aimed to evaluate the effect of selected polymorphisms of the ACTN3, ACE, HIF1A and PPARA genes on the immediate supercompensation training effect of elite Slovak endurance runners and football players compared with a sedentary control group. Adaptation effect levels were evaluated by 10 s continuous vertical jump test parameters measured by Optojump. Genetic polymorphisms were determined by PCR and Sanger sequencing. We found significant differences in the effect of PPARA genotypes in the experimental group. C allele genotypes represented an advantage in immediate supercompensation (p < 0.05). We observed a significant combined effect of multiple genes on immediate supercompensation (p < 0.05): the RR genotype of the ACTN3 gene, the ID genotype of the ACE gene, the Pro/Pro genotype of HIF1A, and the GC and GG genotypes of PPARA genes. In the control group, we found a significant effect (p < 0.05) on immediate supercompensation of the II genotype of the ACE gene and the Pro/Ser genotype of the HIF1A gene. We found significant differences in genotype frequency of ACE (p < 0.01) and PPARA (p < 0.001) genes. We confirmed that individual genetic polymorphisms of ACTN3, ACE, HIF1A and PPARA genes have a different effect on the level of immediate supercompensation of the lower limbs depending on the training adaptation of the probands and the combination of genotypes.

Neurobiological foundations of the formation of behavior and use of psychoactive substances among adolescents (literature review)

Introduction. Adolescence is a critical period over ontogenesis. The complex and heterochronous maturation of various brain structures under the influence of several biologically active substances such as neurotransmitters and hormones, determines the peak of the implementation of risky behavior, including those that promote the gain in the risk of psychoactive substances used by adolescents. At the same time, the variability of behaviour and the degree of risk of use in adolescence is strictly individual and depends on genetic factors. In this regard, the accumulated experience of research on the study of the relationship between neurobiology and genetics in the aspect of the implementation of mental behavioral risk factors becomes relevant. The analysis of scientific literature for the period from 2009 to 2021 in the scientometric databases WoS, Scopus, PubMed, Google Scholar, RSCI was carried out. 59 scientific reports were selected for a systematic review. Modern molecular genetic studies often reveal connections between a specific gene and a wide range of mental brain functions related to different levels of individuality. In the scientific literature, this is explained by the fact that a significant part of the genes is expressed in most brain structures and can be included in various neural systems that provide mental activity. Many gene polymorphisms are established to determine the neurobiology of maturation of the main structures of the brain, which indirectly determines the behavioral risks and risks of substance use over adolescence. Conclusion. Individual genetic polymorphisms affect multidimensional and heterogeneous behavior and character traits, based on neurobiological processes. The study of the effect of gene polymorphism on brain function is highly relevant and promising for research in this area.

Association between interferon-gamma (IFN-γ) gene polymorphisms (+874A/T and +2109A/G), and susceptibility to hepatitis B viral infection (HBV)

Interferon-gamma (IFN-γ) is a chief proinflammatory cytokine with a significant role in the immune response against viral infections. Today there is increasing evidence about the association between individual genetic polymorphisms and cytokines in predicting HBV infection susceptibility. This study aimed to investigate the association between IFN-γ gene polymorphisms and susceptibility to hepatitis B viral infection (HBV), and the impact of these genetic polymorphisms on IFN-γ production. IFN-γ (+874A/T, rs2430561, and +2109A/G, rs1861494) was genotyped by single-stranded polymorphism-polymerase chain reaction (SSP-PCR) in 126 Egyptians with chronic HBV infection and in 100 healthy control subjects. The plasma levels of IFN-γ were measured by Enzyme-linked immunosorbent assay (ELISA). Compared to the control subjects there was a slight increase in +874TT genotype frequency in HBV patients. However, no statistical significance in IFN-γ (+874A/T and +2109A/G) genotype/allele distribution was demonstrated, indicating the lack of association between these SNPs and susceptibility to HBV infection. In +2109A/G, only AG genotype was observed with a complete abrogation of GG and AA genotypes. Haplotypes between different loci on selected genes showed insignificant changes in their frequency in patients and control subjects. HBV patients had a significantly higher level of IFN-γ (P < 0.001) compared to controls. The maximum significant increase in IFN-γ production was observed in subjects harboring the +874TA genotype. As no association could be characterized between the polymorphism in IFN-γ (+874A/T and +2109A/G) and susceptibility to chronic HBV infection, our data support the concept that IFN-γ gene polymorphisms are not predictors of HBV susceptibility in this segment of the Egyptian population.

A Deadly Cargo: Gene Repertoire of Cytotoxic Effector Proteins in the Camelidae.

Cytotoxic T cells and natural killer cells can kill target cells based on their expression and release of perforin, granulysin, and granzymes. Genes encoding these molecules have been only poorly annotated in camelids. Based on bioinformatic analyses of genomic resources, sequences corresponding to perforin, granulysin, and granzymes were identified in genomes of camelids and related ungulate species, and annotation of the corresponding genes was performed. A phylogenetic tree was constructed to study evolutionary relationships between the species analyzed. Re-sequencing of all genes in a panel of 10 dromedaries and 10 domestic Bactrian camels allowed analyzing their individual genetic polymorphisms. The data showed that all extant Old World camelids possess functional genes for two pore-forming proteins (PRF1, GNLY) and six granzymes (GZMA, GZMB, GZMH, GZMK, GZMM, and GZMO). All these genes were represented as single copies in the genome except the GZMH gene exhibiting interspecific differences in the number of loci. High protein sequence similarities with other camelid and ungulate species were observed for GZMK and GZMM. The protein variability in dromedaries and Bactrian camels was rather low, except for GNLY and chymotrypsin-like granzymes (GZMB, GZMH).

Drug-Drug Interactions and Pharmacogenomic Evaluation in Colorectal Cancer Patients: The New Drug-PIN® System Comprehensive Approach.

Drug–drug interactions (DDIs) can affect both treatment efficacy and toxicity. We used Drug-PIN® (Personalized Interactions Network) software in colorectal cancer (CRC) patients to evaluate drug–drug–gene interactions (DDGIs), defined as the combination of DDIs and individual genetic polymorphisms. Inclusion criteria were: (i) stage II-IV CRC; (ii) ECOG PS (Performance status sec. Eastern coperative oncology group) ≤2; (iii) ≥5 concomitant drugs; and (iv) adequate renal, hepatic, and bone marrow function. The Drug-PIN® system analyzes interactions between active and/or pro-drug forms by integrating biochemical, demographic, and genomic data from 110 SNPs. We selected DDI, DrugPin1, and DrugPin2 scores, resulting from concomitant medication interactions, concomitant medications, and SNP profiles, and DrugPin1 added to chemotherapy drugs, respectively. Thirty-four patients, taking a median of seven concomitant medications, were included. The median DrugPin1 and DrugPin2 scores were 42.6 and 77.7, respectively. In 13 patients, the DrugPin2 score was two-fold higher than the DrugPin1 score, with 7 (54%) of these patients experiencing severe toxicity that required hospitalization. On chi-squared testing for any toxicity, a doubled DrugPin2 score (p = 0.001) was significantly related to G3–G4 toxicity. Drug-PIN® software may prevent severe adverse events, decrease hospitalizations, and improve survival in cancer patients.

The Impact of Interferon-γ (IFN-γ) and IFN-γ-Inducible Protein 10 (IP-10) Genes’ Polymorphism on Risk of Hepatitis C Virus–Related Liver Cirrhosis

ABSTRACT Background Today there is increasing evidence concerning the association between individual genetic polymorphisms within proinflammatory cytokines and chronic hepatitis C (CHC) severity. It has been demonstrated that polymorphisms in some genes may significantly predict HCV infected patients’ susceptibility to developing liver cirrhosis or their responsiveness to the treatment. Aim We investigated the influence of single nucleotide polymorphisms (SNPs) in Interferon (IFN-γ) and Interferon Gamma-Inducible Protein 10 (IP-10) genes on cirrhosis risk in HCV-infected patients and their association with response to various direct-acting antiviral drugs (DAAs). Methods IFN-γ (+874T/A, +2109A/G) and IP-10 (−135G/A, −1447A/G) genotypes were determined in 175 CHC Egyptian HCV patients (69 liver cirrhotic and 106 non-cirrhotic patients) using either single-stranded polymorphism polymerase chain reaction (SSP-PCR) or Restriction fragment length-PCR (RFLP-PCR) methods. Results IFN-γ + 874 TA, IP-10 − 135AA, and IP-10 − 1447AA and IP-10 − 1447GG genotypes are increased in patients developing liver cirrhosis compared to non-cirrhotic ones. Although, no statistical significance in their distribution was demonstrated, indicating the lack of association between these SNPs and liver cirrhosis susceptibility in HCV-infected patients. Haplotypes analysis between different loci on all selected genes showed a significant increase in AGGA and TAGA and a significant decrease in TGGA haplotypes in cirrhotic patients. Genotype frequencies at loci −135 and −1447 of IP-10 appeared to be in complete Linkage disequilibrium (LD) (D’ = 0.999, r2 = 0.689). Conclusion Our data support the concept that IFN-γ and IP-10 gene polymorphisms are not predictors of disease progression among Egyptian patients with HCV infection.

The influence of individual genetic polymorphisms on postmenopausal osteoporosis treatment effectiveness

Objective: study of associations between VDR gene rs1544410 and rs10735810 polymorphisms, MCM6 gene rs4988235, CALCR gene rs1801197 one and ibandronate efficacy in women with postmenopausal osteoporosis.Materials and methods: 117 women with postmenopausal osteoporosis were examined for 12 months in the dynamics of treatment with ibandronate. Evaluation of therapy effectiveness was based on indicators of increase in bone mineral density in L1-L4 lumbar vertebrae, as well as left and right femurs.Results: An association of GG genotype of VDR gene rs1544410 polymorphism with low growth rates of mineral density of L1-L4 lumbar vertebrae (3,41 ± 0,60 % versus 5,51 ± 0,78 % in other women; р = 0,036) was established. The effect of other studied polymorphisms (rs10735810 of VDR gene, rs4988235 of MCM6 gene, rs1801197 of CALCR gene) on treatment effectiveness was not found.Conclusion: it is advisable to use obtained results when developing personalized regimens for antiresorptive therapy for women with postmenopausal osteoporosis.

Perioperative Bridging/Cessation of Antiplatelet Agents: 2020 Update

Perioperative management of patients receiving antiplatelet therapy is common and must carefully balance the risk of ischemia or thrombosis with bleeding. Here we describe pathways of platelet aggregation unique to the perioperative period and mechanisms of commonly encountered antiplatelet medications, and review current literature evaluating strategies for antiplatelet management surrounding elective noncardiac and cardiac surgery. Antiplatelet therapies demonstrate unique risk profiles for stent thrombosis and bleeding that may be dependent on individual genetic polymorphisms. Use of scoring systems or point-of-care platelet function assays may identify patients especially vulnerable to alterations in perioperative antiplatelet management, and guide timing of surgery. Prior guidelines, which recommend a minimum 6-month delay in elective surgery for patients receiving dual-antiplatelet therapy following percutaneous coronary intervention (PCI), may be amended to 3 months in certain cases in which newer generation antiplatelet therapies are administered. While use of intravenous bridging agents may reduce platelet reactivity during cardiac surgery, there is no single antiplatelet strategy which consistently reduces rates of major bleeding or cardiovascular events. There is insufficient evidence to support any specific perioperative antiplatelet strategy. Cases should be individualized to balance the risks of stent thrombosis and bleeding. Current recommendations may be modified if the risk of delaying surgery outweighs the risk of stent thrombosis. It is reasonable to guide management by utilizing scoring systems and point-of-care platelet function assays.

Anna A Artaryan: paediatric neurosurgeon who created the first chair in the specialty

<h3>Background</h3> Multiple Sclerosis (MS) is the most common demyelinating disorder. Still today its pathogenesis is not well known, but there are several drugs to slow down disease progression. Interferon-B (IFN-B)...

Promoting self-management of breast and nipple pain in breastfeeding women: Protocol of a pilot randomized controlled trial.

The majority of women experience pain during breastfeeding initiation with few strategies to manage breast and nipple pain. In fact, women cite breast and nipple pain as among the most common reasons for breastfeeding cessation. To address this important issue, we developed a breastfeeding self-management (BSM) intervention, based on the Individual and Family Self-Management Theory Framework. In this framework, self-management is conceptualized as a process in which women use knowledge, beliefs, and social facilitation to achieve breastfeeding goals. The purpose of this longitudinal pilot randomized controlled trial was to test the feasibility, acceptability, and preliminary efficacy of the BSM intervention with women initiating breastfeeding. Recruitment of 60 women intending to breastfeed occurred within 48 hr of delivery and women were randomized to either the intervention or usual care group. The BSM intervention group received BSM education modules that included information of how to manage breast and nipple pain and self-management support through biweekly texting from the study nurse, and were asked to complete a daily breastfeeding journal. Primary outcomes measured at baseline, 1, 2, and 6 weeks will be used to (a) evaluate feasibility, acceptability, and preliminary efficacy of the BSM intervention, and (b) assess the influence of protective and risk factors of breastfeeding pain (including individual genetic polymorphisms related to pain sensitivity) on process variables for self-management of breastfeeding and breastfeeding pain, and on proximal (breastfeeding pain severity and interference, breastfeeding frequency) and distal outcomes (breastfeeding exclusivity and duration and general well-being).

Vitamin D and the Development of Atopic Eczema.

A “vitamin D hypothesis” has been proposed to explain the increased prevalence of eczema in regions with higher latitude. This review focuses on the current available evidence with regard to the possible effect of vitamin D on the development of atopic eczema. Observational studies have indicated a link between vitamin D status and eczema outcomes, including lower serum vitamin D levels associated with increased incidence and severity of eczema symptoms. Vitamin D is known to have a regulatory influence on both the immune system and skin barrier function, both critical in the pathogenesis of eczema. However heterogeneous results have been found in studies to date investigating the effect of vitamin D status during pregnancy and infancy on the prevention of eczema outcomes. Well-designed, adequately powered, randomised controlled trials are needed. The study design of any new intervention trials should measure vitamin D levels at multiple time points during the intervention, ultraviolet (UV) radiation exposure via the use of individual UV dosimeters, and investigate the role of individual genetic polymorphisms. In conclusion, the current available evidence does not allow firm conclusions to be made on whether vitamin D status affects the development of atopic eczema.

Association between GSTP1, GSTM1, GSTT1 genetic polymorphisms and urinary styrene phenyl hydroxyethyl mercapturic acids level

To investigate the relationship between genetic polymorphisms of glutathione S-transferase P1 (GSTP1), glutathione S-transferase M1 (GSTM1), and glutathione S-transferase T1 (GSTT1) and urinary level of mercapturic acids of styrene (PHEMAs) in workers exposed to styrene. One hundred and twenty-six workers exposed to styrene were selected as exposure group, and 150 workers without styrene exposure as the control group; all the workers came from a locomotive shell production factory in Shandong Province, China. The PCR-RFLP technique was applied to analyze the individual genetic polymorphisms of GSTP1; the multiplex PCR technique was used to investigate the genetic polymorphisms of GSTM1 and GSTT1; the relationship between genetic polymorphisms of GSTP1, GSTM1, and GSTT1 and urinary level of PHEMAs in workers exposed to styrene was statistically analyzed. The three genotypes investigated in the study had a distribution in accordance with the Chinese population. With exposure to high- concentration styrene, the individuals carrying GSTP1 (exon5, A105G) AA genotype (wildtype) had a significantly higher urinary level of PHEMAs (43.58 mg/g) than those with mutant genotypes AG (29.769 mg/g) and GG (30.245 mg/g); the urinary level of PHEMAs in individuals carrying wild-type GSTM1 genotype was significantly higher than that in individuals carrying deficient-type GSTM1 genotype (40.197 mg/g vs 28.866 mg/g, P < 0.05); no significant difference in urinary level of PHEMAs was found between individuals carrying wild-type GSTT1 genotype and deficient-type GSTT1 genotype. There was no significant relationship between the three gene polymorphisms and urinary level of PHEMAs in the control group. The genetic polymorphisms of GSTP1 and GSTM1 may be related to urinary level of PHEMAs in workers exposed to styrene.

Connectomics Sheds New Light on Alzheimer’s Disease

Connectomics Sheds New Light on Alzheimer’s Disease

Induction of sister chromatid exchange by acrylamide and glycidamide in human lymphocytes: Role of polymorphisms in detoxification and DNA-repair genes in the genotoxicity of glycidamide

Acrylamide (AA) is a probable human carcinogen generated in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), formed via epoxidation, presumably mediated by cytochrome P450 2E1, is considered to be the active metabolite that plays a central role in the genotoxicity of AA. The aim of this work was to evaluate the cytogenetic damage induced by AA and GA in cultured human lymphocytes by use of the sister chromatid exchange (SCE) assay. Furthermore, this report addresses the role of individual genetic polymorphisms in key genes involved in detoxification and DNA-repair pathways (BER, NER, HRR and NHEJ) on the induction of SCE by GA. While AA induced the number of SCE/metaphase only slightly, especially for the highest concentration tested (2000μM), GA markedly induced SCEs in a concentration-dependent manner up to concentrations of 750μM, leading to an increase in SCEs of up to about 10-fold compared with controls. By combining DNA damage in GA-treated lymphocytes and data on polymorphisms, associations between the induction of SCEs with GSTP1 (Ile105Val) and GSTA2 (Glu210Ala) genotypes are suggested.

CYP3A5 Polymorphism Effect on Cyclosporine Pharmacokinetics in Living Donor Renal Transplant Recipients: Analysis by Population Pharmacokinetics

Cyclosporine is often used to prevent allograft rejection in renal transplant recipients. However, cyclosporine has a narrow therapeutic window and large variability in its pharmacokinetics. Individual characteristics and genetic polymorphisms can cause the variation. Hence, it is important to determine the cause(s) of the variation in cyclosporine pharmacokinetics. To our knowledge, this is the first reported population pharmacokinetic study of cyclosporine in living donor renal transplant recipients that considered the genetic polymorphism as a covariate. To build a population pharmacokinetic model of cyclosporine in living donor renal transplant recipients and identify covariates including CYP3A5*3, ABCB1 genetic polymorphisms that affect cyclosporine pharmacokinetic parameters. Clinical characteristics and cyclosporine concentration data for 69 patients who received cyclosporine-based immunosuppressive therapy after living donor renal transplantation were collected retrospectively for up to 400 postoperative days. CYP3A5*1/*3 and ABCB1C1236T, G2677T/A, C3435T geno-typing was performed. A population pharmacokinetic analysis was conducted using a NONMEM program. After building the final model, 1000 bootstrappings were performed to validate the final model. In total, 2034 blood samples were collected. A 1-compartment open model with first-order absorption and elimination was chosen to describe the pharmacokinetics of cyclosporine. A population pharmacokinetic analysis showed that postoperative days, sex, and CYP3A5 genotype significantly affected the pharmacokinetics of cyclosporine. The final estimate of mean clearance was 56 L/h, and the mean volume of distribution was 4650 L. The interindividual variability for these parameters was 22.98% and 51.48%, respectively. Using the present model to calculate the dose of cyclosporine with CYP3A5 genotyping can be possible for the patients whose cyclosporine concentration is not within the therapeutic range even with therapeutic drug monitoring.

Temporal dynamics and genetic control of transcription in the human prefrontal cortex

Previous investigations have combined transcriptional and genetic analyses in human cell lines, but few have applied these techniques to human neural tissue. To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application (http://www.libd.org/braincloud).

Serum NT pro-BNP and individual genetic polymorphisms as predictors of trastuzumab-related cardiotoxicity.

TPS121 Background: Trastuzumab-related cardiotoxicity (TRC) may lead to premature cessation of adjuvant trastuzumab (T) amongst women with early stage HER2-positive breast cancer (ESHBC) and hence ...

Abstract 4199: Genetic variation in the in vitro genotoxic response to glycidamide and gene expression of DNA repair genes

Abstract Acrylamide (AA) is a suspected human carcinogen generated in carbohydrate-rich foodstuff upon heating. Glycidamide (GA), formed via epoxidation presumably mediated by cytochrome P450 2E1, is thought to be the active metabolite that plays a central role in AA genotoxicity. The high levels of AA that are orally consumed could be an additional factor for global cancer risk. However, cancer risk estimation in population is still problematic and the mechanisms of DNA repair triggered by GA are still poorly understood. The aim of this work was to evaluate the role of DNA repair genes in the genotoxicity induced by GA in human cells, using complementary methodologies. For this purpose, the effect of GA (250 µM) in cultured human lymphocytes from healthy non-smoker individuals (n=13) was assessed using the sensitive sister-chromatid exchange assay (SCE, 46 h in vitro exposure). GA was found to be genotoxic, with a large inter-individual variation. Therefore we studied the possible influence of individual genetic polymorphisms of key genes codifying for DNA repair enzymes related to the BER (XRCC1, OGG1, PARP1, PARP4, APEX1 and MUTYH), NER (RAD23B, ERCC1, ERCC2, ERCC4, ERCC5, ERCC6 and XPC) and HRR (RAD51, NBS, XRCC3 and XRCC2) pathways. No relevant associations between SCE/cell levels and the individual genetic polymorphisms were found. However, the only individual with the ERCC1 Q504K polymorphism revealed a significant increase in GA-induced levels of SCE/cell (p&amp;lt;0.03). We further studied the effect of the same concentration of GA in peripheral white blood cells from healthy individuals (n=25) using the comet assay (CA, 1 hour in vitro incubation). GA also showed to be genotoxic. The % DNA in Tail for all individuals was analysed considering the abovementioned polymorphisms. In this assay, the MUTYH H335Q was found to influence the repair capacity of GA, being the variant genotype associated with an increased damage in the comet assay (6.1± 1.7 heterozygous versus 11.9 ± 1.8 homozygous variant; p&amp;lt;0.001). Finally, a different strategy focusing on the role of DNA repair enzymes upon GA treatment was used. The non-malignant mammary cell line MCF10A was exposed to GA (10 µM) for 24 h and gene expression was studied using RT2 ProfilerTM PCR Array: Human DNA Damage Signalling Pathway by SABiosciencesTM. Concerning gene expression results, GA at this lower concentration level did not influence the expression of the genes considered when compared to respective non-treated controls. Further studies should be conducted in order to test other exposure periods and use other human cell types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4199. doi:10.1158/1538-7445.AM2011-4199