West Syndrome and the Importance of Routine Physical Examinations and Parental Education: A Case Report.

West syndrome (WS), also known as infantile spasms, is a severe form of epileptic disorder of infancy and early childhood. It was first described by William West in 1841. Children with WS exhibit a triad of myoclonic-tonic seizures (spasms), a distinct electroencephalogram (EEG) pattern known as hypsarrhythmia and psychomotor development arrest. WS is classified into three main categories as symptomatic, idiopathic and cryptogenic based on etiological factors. The long-term prognosis depends on the etiological cause, but generally has a poor prognosis, and is associated with impaired development, neurologic structural anomalies, autism spectrum disorder and death. Treatment guidelines from the American Academy of Neurology and Child Neurology Society recommend that adrenocorticotropic hormone (ACTH) and vigabatrin are possibly effective in the cessation of spasms and hypsarrhythmia. We report an incidental diagnosis of WS in a six-month-old male baby that went to the Pediatric Emergency Department due to upper respiratory tract symptoms. The diagnosis was made after the development of spasms during a medical examination. This case highlights the importance of early diagnosis, parental education and prompt effective treatment as it may improve prognosis.

RAD52 Functions in Homologous Recombination and Its Importance on Genomic Integrity Maintenance and Cancer Therapy.

Genomes are continually subjected to DNA damage whether they are induced from intrinsic physiological processes or extrinsic agents. Double-stranded breaks (DSBs) are the most injurious type of DNA damage, being induced by ionizing radiation (IR) and cytotoxic agents used in cancer treatment. The failure to repair DSBs can result in aberrant chromosomal abnormalities which lead to cancer development. An intricate network of DNA damage signaling pathways is usually activated to eliminate these damages and to restore genomic stability. These signaling pathways include the activation of cell cycle checkpoints, DNA repair mechanisms, and apoptosis induction, also known as DNA damage response (DDR)-mechanisms. Remarkably, the homologous recombination (HR) is the major DSBs repairing pathway, in which RAD52 gene has a crucial repairing role by promoting the annealing of complementary single-stranded DNA and by stimulating RAD51 recombinase activity. Evidence suggests that variations in RAD52 expression can influence HR activity and, subsequently, influence the predisposition and treatment efficacy of cancer. In this review, we present several reports in which the down or upregulation of RAD52 seems to be associated with different carcinogenic processes. In addition, we discuss RAD52 inhibition in DDR-defective cancers as a possible target to improve cancer therapy efficacy.

Pharmacogenomics in epithelial ovarian cancer first-line treatment outcome: validation of GWAS-associated NRG3 rs1649942 and BRE rs7572644 variants in an independent cohort.

The identification of predictive biomarkers for the first-line treatment of epithelial ovarian cancer (EOC) remains a challenge. Although genome-wide association studies (GWAS) have identified several genetic polymorphisms as predictors of EOC clinical outcome, the subsequent validation has not yet been performed. This study aims to validate the influence of Neuregulin 3 (NRG3) rs1649942 and Brain and reproductive organ-expressed (TNFRSF1A modulator) (BRE) rs7572644 GWAS-identified variants in an independent cohort of EOC patients from the North region of Portugal (n = 339) submitted to first-line treatment. Polymorphism genotypes were determined by real-time PCR using validated assays. Patients carrying the NRG3 rs1649942 A allele presented a significantly longer overall survival (OS) when compared to GG-genotype patients (log-rank test, P = 0.011) in the FIGO IV stage subgroup. No impact was observed for early-stage patients or considering disease-free survival (DFS) as an outcome. For FIGO I/II stage patients, BRE rs7572644 C allele carriers exhibit a decreased OS (P = 0.014) and DFS (P = 0.032) when compared to TT-homozygous patients. Furthermore, a Multivariate Cox regression analysis revealed a three-fold increase in the risk of death (HR, 3.09; P = 0.015) and recurrence (HR, 3.33; P = 0.009) for FIGO I/II C allele carriers. No significant impact was observed for late-stage patients. The BRE rs7572644 and NRG3 rs1649942 genetic variants were validated in an independent cohort of EOC Portuguese patients, particularly in specific subgroups considering FIGO staging. Further functional post-GWAS analyses are indispensable to understand the biological mechanisms underlying the observed results.

Canine mammary tumor risk is associated with polymorphisms in RAD51 and STK11 genes.

Cancer is a complex disease involving genetic and phenotypic changes. Several single nucleotide polymorphisms (SNPs) have been associated with the risk of breast cancer development in women; however, little is known regarding their influence on canine mammary tumor risk. We assessed the influence of SNPs in genes related to human breast cancer susceptibility, with respect to the risk of development of mammary tumors in dogs. Sixty-seven canine SNPs in proto-oncogenes, tumor suppressor genes, genes involved in DNA repair, and in hormonal metabolism were evaluated in 212 bitches with mammary tumors and in 161 bitches free of mammary neoplasia. A significant association with mammary neoplasia risk was identified for 2 SNPs in RAD51 ( rs23623251 and rs23642734) and one SNP in the STK11 gene ( rs22928814). None of the other SNPs were related to the risk of mammary tumor development. The identification of genetic profiles associated with risk of mammary neoplasia is of great importance, supporting the implementation of specific clinical management strategies in high-risk animals.

TP53 Arg72Pro polymorphism is associated with increased overall survival but not response to therapy in Portuguese/Caucasian patients with advanced cervical cancer.

Identification of mechanisms that influence the therapeutic response and survival in patients with cancer is important. It is known that the genetic variability of the host, including presence of genetic polymorphisms in genes involved in DNA damage response, serves a crucial role in the prognosis of these patients. The present hospital-based retrospective cohort study aimed to evaluate the influence of TP53 Arg72Pro (rs1042522) polymorphism in the clinical outcome of 260 Caucasian patients diagnosed with cervical cancer and treated with concomitant radiotherapy and chemotherapy. The polymorphism genotyping was assessed using allelic discrimination by quantiative polymerase chain reaction. The results indicate that the TP53 Arg72Pro polymorphism did not significantly impact the response to therapy (P=0.571) nor disease-free survival (P=0.081). However, the polymorphism did influence overall survival, as increased median survival time was observed for patients carrying Arg/Pro genotype when compared with patients with Arg/Arg and Pro/Pro genotypes (126 months vs. 111 months, respectively; P=0.047). To conclude, the present findings suggest that a pharmacogenomic profile based on the genetic background of patients, including the analysis of the TP53 genotypes, may individualize treatment nad assist in the selection of therapies that may improve clinical outcome and lower toxicity for the patients.

Relationship between clinical toxicities and ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms in cervical cancer patients.

BACKGROUND: Several studies have suggested that there are single nucleotide polymorphisms (SNPs) that can be considered potential biomarkers in the prognosis and therapeutic response of cancer patients. The present study investigated the association between ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms and clinical toxicities induced by chemoradiotherapy (CRT) in cervical cancer. METHODS: This hospital-based retrospective cohort study included 260 patients with cervical cancer, FIGO stages Ib2-IVa, who underwent CRT (cisplatin). Genetic polymorphisms analysis was performed by allelic discrimination with real-time polymerase chain reaction (RT-PCR). RESULTS: Our results indicated a link between ERCC1 rs3212986 and the onset of late gastrointestinal toxicity (p = 0.038). Furthermore, using a recessive model (AA vs. CC/CA), we found that patients carrying AA homozygous genotype presented a fourfold increased risk of developing late gastrointestinal toxicity when compared with patients with the C allele (odds ratio = 3.727, 95% confidence interval, 1.199-11.588; p = 0.017). No association was found regarding the XRCC3 rs861539 polymorphism and any clinical toxicity event. CONCLUSIONS: This is the first study evaluating the relationship between these polymorphisms and clinical toxicities in cervical cancer patients submitted to CRT with cisplatin. These results may contribute toward a better understanding of the influence of genetic polymorphisms in genes associated with DNA repair in the clinical response to CRT of patients with cervical cancer.

Rethinking ovarian cancer genomics: where genome-wide association studies stand?

Genome-wide association studies (GWAS) allow the finding of genetic variants associated with several traits. Regarding ovarian cancer (OC), 15 GWAS have been conducted since 2009, with the discovery of 49 SNPs associated with disease susceptibility and 46 with impact in the clinical outcome of patients (p < 5.00 × 10-2). Among them, 14 variants reached the genome-wide significance (p < 5.00 × 10-8). Despite the results obtained, they should be validated in independent sets. So far, five validation studies have been conducted which could confirm the association of 12 OC susceptibility SNPs. Consequently, post-GWAS studies are crucial unravel the biological plausibility of GWAS' findings and the allelic spectrum of OC.

Genetic variants as ovarian cancer first-line treatment hallmarks: A systematic review and meta-analysis.

BACKGROUND: The potential predictive value of genetic polymorphisms in ovarian cancer first-line treatment is inconsistently reported. We aimed to review ovarian cancer pharmacogenetic studies to update and summarize the available data and to provide directions for further research. METHODS: A systematic review followed by a meta-analysis was conducted on cohort studies assessing the involvement of genetic polymorphisms in ovarian cancer first-line treatment response retrieved through a MEDLINE database search by November 2016. Studies were pooled and summary estimates and 95% confidence intervals (CI) were calculated using random or fixed-effects models as appropriate. RESULTS: One hundred and forty-two studies gathering 106871 patients were included. Combined data suggested that GSTM1-null genotype patients have a lower risk of death compared to GSTM1-wt carriers, specifically in advanced stages (hazard ratio (HR), 0.68; 95% CI, 0.48-0.97) and when submitted to platinum-based chemotherapy (aHR, 0.61; 95% CI, 0.39-0.94). ERCC1 rs11615 and rs3212886 might have also a significant impact in treatment outcome (aHR, 0.67; 95% CI, 0.51-0.89; aHR, 1.28; 95% CI, 1.01-1.63, respectively). Moreover, ERCC2 rs13181 and rs1799793 showed a distinct ethnic behavior (Asians: aHR, 1.41; 95% CI, 0.80-2.49; aHR, 1.07; 95% CI, 0.62-1.86; Caucasians: aHR, 0.10; 95% CI, 0.01-0.96; aHR, 0.18; 95% CI, 0.05-0.68, respectively). CONCLUSION(S): The definition of integrative predictive models should encompass genetic information, especially regarding GSTM1 homozygous deletion. Justifying additional pharmacogenetic investigation are variants in ERCC1 and ERCC2, which highlight the DNA Repair ability to ovarian cancer prognosis. Further knowledge could aid to understand platinum-treatment failure and to tailor chemotherapy strategies.

Base excision repair pathway: PARP1 genotypes as modulators of therapy response in cervical cancer patients.

CONTEXT: Genetic polymorphisms in genes of the base excision repair (BER) pathway appear to modulate the therapy response of cancer patients. PARP1 protein recognizes the DNA strand damage and facilitates the subsequent recruitment of BER proteins. Few studies have reported an association between PARP1 Val762Ala polymorphism (rs1136410) and cancer therapy response. OBJECTIVE: The purpose of our study was to determine whether PARP1 Val762Ala polymorphism have prognostic value in patients with cervical cancer. MATERIALS AND METHODS: Two hundred and sixty adult patients, with histologically confirmed cervical cancer, at FIGO-stages IB2-IVA, primarily treated with concurrent chemotherapy (cisplatin) and radiotherapy. Overall survival (OS) and disease-free survival (DFS) were the primary end points of the analysis. The PARP1 Val762Ala genetic variants were analyzed by allelic discrimination by real-time PCR. RESULTS: We observed that peri- and postmenopausal women carrying the C-allele present a statistically significant lower OS and DFS (log-rank test, p = 0.008 and p = 0.006, respectively) among those with early stage cervical cancer. Cox regression analysis confirmed these results, after adjustment for other prognostic factors (for OS: HR, 3.70; 95%CI, 1.32-10.38; p = 0.013 and for DFS: HR, 3.97; 95%CI, 1.59-9.93; p = 0.003). CONCLUSIONS: This is the first study evaluating the effect of PARP1 Val762Ala polymorphism in treatment response in cervical cancer patients. PARP1 genotypes may contribute as an independent prognostic factor in cervical cancer, being useful in predicting the clinical outcome.

Improvement of a predictive model in ovarian cancer patients submitted to platinum-based chemotherapy: implications of a GST activity profile.

PURPOSE: The success of chemotherapy in ovarian cancer (OC) is directly associated with the broad variability in platinum response, with implications in patients survival. This heterogeneous response might result from inter-individual variations in the platinum-detoxification pathway due to the expression of glutathione-S-transferase (GST) enzymes. We hypothesized that GSTM1 and GSTT1 polymorphisms might have an impact as prognostic and predictive determinants for OC. METHODS: We conducted a hospital-based study in a cohort of OC patients submitted to platinum-based chemotherapy. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. RESULTS: GSTM1-null genotype patients presented a significantly longer 5-year survival and an improved time to progression when compared with GSTM1-wt genotype patients (log-rank test, P = 0.001 and P = 0.013, respectively). Multivariate Cox regression analysis indicates that the inclusion of genetic information regarding GSTM1 polymorphism increased the predictive ability of risk of death after OC platinum-based chemotherapy (c-index from 0.712 to 0.833). Namely, residual disease (HR, 4.90; P = 0.016) and GSTM1-wt genotype emerged as more important predictors of risk of death (HR, 2.29; P = 0.039; P = 0.036 after bootstrap). No similar effect on survival was observed regarding GSTT1 polymorphism, and there were no statistically significant differences between GSTM1 and GSTT1 genotypes and the assessed patients' clinical-pathological characteristics. CONCLUSION: GSTM1 polymorphism seems to have an impact in OC prognosis as it predicts a better response to platinum-based chemotherapy and hence an improved survival. The characterization of the GSTM1 genetic profile might be a useful molecular tool and a putative genetic marker for OC clinical outcome.

DNA repair system and renal cell carcinoma prognosis: under the influence of NBS1.

Nibrin (NBS1) is a protein involved in the maintenance of genomic stability and in DNA repair mechanisms. The NBS1 E185Q polymorphism (rs1805794) has been investigated in several studies, including its influence in the pathogenesis of renal cell carcinoma (RCC), although its prognostic value is still not determined for these patients. The purpose of the present work was to determine the role of NBS1 E185Q polymorphism as a prognostic factor/genetic marker of survival in patients with RCC. We conducted a hospital-based study analyzing 172 caucasian patients with histopathological diagnosis of RCC, for which polymorphism genotyping was performed by TaqMan(®) Allelic Discrimination methodology. In this study, we have found that male patients, non-metastatic at diagnosis and NBS1 C allele carriers (GC/CC) showed a lower 5-years survival when compared with GG genotype patients (P = 0.045). Furthermore, for carriers of low-activity NBS1 C allele, multivariate Cox regression analysis revealed almost a fourfold increase in risk of death at 5 years, after adjustment for age, histological type, Fuhrman's grade, tumor size and vascular permeation (HR 3.92; 95 % CI 1.33-11.57; P = 0.013). There were no statistically significant differences between the NBS1 E185Q genotypes and the assessed patients' clinical-pathological characteristics. Our results demonstrate for the first time the impact of NBS1 E185Q polymorphism in RCC prognosis suggesting that, for RCC male patients non-metastatic at diagnosis, this polymorphism might be a putative genetic marker in the clinical outcome.

Interleukin-1ß genotype and circulating levels in cancer patients: metastatic status and pain perception.

OBJECTIVES: Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients. DESIGN AND METHODS: Serum IL-1α/ß levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters. RESULTS: IL-1ß rs1143634 homozygous for T allele were associated with lower levels of IL1-ß (p=0.032, Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06, Fisher's Exact Test). Also, IL1-ß levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1ß individuals (OR=4.074, p=0.010, Pearson χ(2) test). Among the female patients presenting metastatic disease and carriers of the TT genotype we observed a trend to lower levels of IL1-ß (p=0.053, Pearson χ(2) test). CONCLUSIONS: Our results indicate that genetic variation at IL1-ß gene may influence serum levels of IL1-ß, with proportional consequences in cancer-related pain.

Restoring TGFß1 pathway-related microRNAs: possible impact in metastatic prostate cancer development.

In developed countries, prostate cancer (PC) is the neoplasia more frequently diagnosed in men. The signaling pathway induced by the transforming growth factor ß1 (TGFß1) has an important role in cell growth, differentiation, and development, the downregulation of this pathway being associated with cancer development. In PC, the activation of this signaling pathway is lost, resulting in favoring of tumor growth, proliferation, and evasion of apoptosis. Several studies have shown that microRNAs (miRNAs), small non-coding RNA, are closely associated with the development, invasion, and metastasis, suggesting that they have a critical role in cancer development. Recently, Smad proteins, the signal transducers of the TGFß1 signaling pathway, were found to regulate miRNA expression, through both transcriptional and posttranscriptional mechanisms. In this review, we summarize the mechanisms underlying Smad-mediated regulation of miRNA biogenesis and the effects on cancer development, particularly in PC. We identify that TGFß1-related miR-143, miR-145, miR-146a, and miR-199a may have a key role in the development of prostate cancer metastasis and the restoration of their expression may be a promising therapeutic strategy for PC treatment.

Common genetic polymorphisms in the ABCB1 gene are associated with risk of major depressive disorder in male Portuguese individuals.

Major depressive disorder (MDD) is a highly prevalent disorder, which has been associated with an abnormal response of the hypothalamus-pituitary-adrenal (HPA) axis. Reports have argued that an abnormal HPA axis response can be due to an altered P-Glycoprotein (P-GP) function. This argument suggests that genetic polymorphisms in ABCB1 may have an effect on the HPA axis activity; however, it is still not clear if this influences the risk of MDD. Our study aims to evaluate the effect of ABCB1 C1236T, G2677TA and C3435T genetic polymorphisms on MDD risk in a subset of Portuguese patients. DNA samples from 80 MDD patients and 160 control subjects were genotyped using TaqMan SNP Genotyping assays. A significant protection for MDD males carrying the T allele was observed (C1236T: odds ratio (OR)=0.360, 95% confidence interval [CI]: [0.140-0.950], p=0.022; C3435T: OR=0.306, 95% CI: [0.096-0.980], p=0.042; and G2677TA: OR=0.300, 95% CI: [0.100-0.870], p=0.013). Male Portuguese individuals carrying the 1236T/2677T/3435T haplotype had nearly 70% less risk of developing MDD (OR=0.313, 95% CI: [0.118-0.832], p=0.016, FDR p=0.032). No significant differences were observed regarding the overall subjects. Our results suggest that genetic variability of the ABCB1 is associated with MDD development in male Portuguese patients. To the best of our knowledge, this is the first report in Caucasian samples to analyze the effect of these ABCB1 genetic polymorphisms on MDD risk.

Renal cell carcinoma development and miRNAs: a possible link to the EGFR pathway.

Renal cell carcinoma (RCC) is the most common solid cancer of the adult kidney and the majority of RCC cases are detected accidentally. This reality and the nonexistence of a standard screening test contribute to the fact that one third of patients are diagnosed with local invasive disease or metastatic disease. miRNAs are a family of small ncRNAs that regulate gene expression and have been identified as key regulators in many biological processes including cell development, differentiation, apoptosis and proliferation. The EGF receptor signaling pathway is usually deregulated in cancer and it is suggested to have an important role in RCC. Further studies are needed to characterize deregulation of this pathway during RCC development. In this review we highlight some potential miRNAs that could be involved in the modulation of the EGF receptor pathway and consequently in RCC development.

Influence of CYP3A4 genotypes in the outcome of serous ovarian cancer patients treated with first-line chemotherapy: implication of a CYP3A4 activity profile.

CYP3A4 is a key enzyme involved in the metabolism of numerous compounds, such as paclitaxel, and its activity shows an extensive inter-individual variation which can influence treatment response. The study's purpose was to investigate the potential predictive role of a CYP3A4 profile (CYP3A4*1B, rs2740574 and CYP3A4*22, rs35599367) in serous ovarian cancer patients treated with first-line chemotherapy (paclitaxel and cisplatin or carboplatin), after cytoreductive surgery. CYP3A4*1B and CYP3A4*22 genotypes were determined by Nested PCR-RFLP and Taqman® Allelic Discrimination, respectively. We observed that the mean survival rates were statistically different according the patients CYP3A4 genotypes. The group of patients carrying the CYP3A4*1B G allele present a decreased mean survival rate when compared with AA genotype patients (103.93 and 134.44 months, respectively, p = 0.010). This result is consistent after multivariate Cox regression analysis (HR, 2.15; 95% CI, 1.03-4.52; p = 0.043). The combination of CYP3A4*1B and CYP3A4*22 polymorphisms result in the definition of a CYP3A4 activity profile: the group of patients with a higher CYP3A4 activity profile had significantly diminished survival when compared with patients with a lower CYP3A4 activity profile (101.06 and 134.44 months, respectively, p = 0.012). Multivariate Cox regression analysis revealed a diminished overall survival time for patients with CYP3A4 high activity profile (HR, 2.29; 95% CI, 1.05-5.02; p = 0.038). The definition of a CYP3A4 activity profile resulted in the increase of prediction ability, using Harrels's concordance indexes (C-index from 0.617 to 0.626). To conclude, our results demonstrate an association between CYP3A4*1B and a diminished overall survival of patients with serous ovarian cancer. The definition of a CYP3A4 activity profile proved to be benefic and the CYP3A4 high activity profile was associated with a lower overall survival. We consider that the definition of a CYP3A4 activity profile might be useful as molecular marker for predicting the clinical outcome of serous ovarian cancer patients.

Improvement of a predictive model of castration-resistant prostate cancer: functional genetic variants in TGFß1 signaling pathway modulation.

Prostate cancer (PC) is the most frequently diagnosed cancer in men. The acquisition of castration-resistant (CR) phenotype is associated with the activation of signaling pathways mediated by growth factors. The TGFß1 and its receptors have an important role in tumor progression, being the pro-apoptotic function modulated by the expression of TGFBR2. A single nucleotide polymorphism -875 G > A in TGFBR2 gene has been described, which may influence the expression levels of the receptor. Our purpose was to investigate the potential role of TGFBR2-875G>A in PC risk and in the response to androgen deprivation therapy (ADT). TGFBR2-875G>A polymorphism was studied by allelic discrimination using real-time polymerase chain reaction (PCR) in 891 patients with PC and 874 controls. A follow-up study was undertaken to evaluate response to ADT. The TGFBR2 and SMAD7 mRNA expression were analyzed by a quantitative real-time PCR. We found that TGFBR2-875GG homozygous patients present lower expression levels of TGFBR2 mRNA (AA/AG: 2(-ΔΔCT) =1.5, P=0.016). GG genotype was also associated with higher Gleason grade (OR=1.51, P=0.019) and increased risk of an early relapse after ADT (HR=1.47, P=0.024). The concordance (c) index analysis showed that the definition of profiles that contains information regarding tumor characteristics associated with genetic information present an increased capacity to predict the risk for CR development (c-index model 1: 0.683 vs model 2: 0.736 vs model 3: 0.746 vs model 4: 0.759). The TGFBR2-875G>A contribution to an early relapse in ADT patients, due to changes in mRNA expression, supports the involvement of TGFß1 pathway in CRPC. Furthermore, according to our results, we hypothesize the potential benefits of the association of genetic information in predictive models of CR development.

DNA repair and cytotoxic drugs: the potential role of RAD51 in clinical outcome of non-small-cell lung cancer patients.

Many of the cytotoxic drugs used in the treatment of non-small-cell lung carcinoma patients can interfere with DNA activity and the definition of an individual DNA repair profile could be a key strategy to achieve better response to chemotherapeutic treatment. Although DNA repair mechanisms are important factors in the prevention of carcinogenesis, these molecular pathways are also involved in therapy response. RAD51 is a crucial element in DNA repair by homologous recombination and has been shown to interfere with the prognosis of patients treated with chemoradiotherapy. There is increasing evidence that genetic polymorphisms in repair enzymes can influence DNA repair capacity and, consequently, affect chemotherapy efficacy. We conducted this review to show the possible influence of the RAD51 genetic variants in damage repair capacity and treatment response in non-small-cell lung carcinoma patients.

The impact of GGH -401C>T polymorphism on cisplatin-based chemoradiotherapy response and survival in cervical cancer.

AIMS: Cervical cancer is the third most frequent cancer in women worldwide, mostly treated with cisplatin-based chemoradiotherapy. Since it is known that folate metabolism might interfere with cisplatin effectiveness, we intended to study the influence of the Gamma Glutamyl Hydrolase -401C>T polymorphism in treatment response in cervical cancer. METHODS: We retrospectively reviewed the clinical data of 167 patients with bulky cervical cancer submitted to cisplatin-based chemoradiotherapy. The genotypes of GGH -401C>T SNP were determined by real-time PCR and statistical analysis was performed by χ(2) test and survival analysis. RESULTS: The genotypes of GGH-401C>T were significantly associated with the response to platinum-based chemoradiotherapy. Treatment response was higher in patients carrying the CC genotype, who presented a significant increased chance of treatment response (survival time in months/genotype: 91 for CC Vs 72 for CT/TT; p=0.035, log rank test). A Cox regression analysis accordingly showed that the presence of the T allele was significantly linked to a worse treatment response (HR=3.036; CI 95% 1.032-8.934, p=0.044). CONCLUSIONS: The results of our study suggested the potential interest of GGH -401C>T as a predictive factor of the outcome of cervical carcinoma treated with cisplatin-based chemoradiotherapy.