Fabiana Granja

Smoking and susceptibility to thyroid cancer: an inverse association with CYP1A1 allelic variants

In contrast to most human malignancies, epidemiologic studies have frequently reported a reduced risk of differentiated thyroid cancer in tobacco consumers. Cytochrome P4501A1 (CYP1A1) gene variants may be related to an increased capacity to activate polycyclic aromatic hydrocarbons, producing highly reactive electrophilic intermediates that might damage DNA. Hence, the germline inheritance of a wild-type CYP1A1 gene may decrease the susceptibility for thyroid cancer. The present study was designed to investigate CYP1A1 (m1 and m2) role in thyroid tumorigenesis and its connection with GSTM1, GSTT1, GSTP1, GSTO1, and codon 72 of p53 genotypes. A total of 248 patients with thyroid nodules, including 67 benign goiters, 13 follicular adenomas, 136 papillary carcinomas, and 32 follicular carcinomas, and 277 controls with similar ethnic backgrounds were interviewed on their lifetime dietary and occupational histories, smoking habit, previous diseases, and other anamnestic data. DNA was extracted from a blood sample and submitted to PCR-restriction fragment length polymorphism assays. The wild-type CYP1A1m1 genotype was more frequent among papillary carcinoma patients (74.26%) than in the control population (62.45%; P=0.0147), reducing the risk for this type of cancer (odds ratio=0.564; 95% confidence interval=0.357-0.894). A multiple logistic regression analysis showed an inverse correlation between cigarette smoking (P=0.0385) and CYP1A1 germline inheritance (P=0.0237) with the susceptibility to papillary carcinomas. We were not able to find any correlation between smoking, clinical features, parameters of aggressiveness at diagnosis or during follow-up, and any of the GST or CYP genotypes considered separately or in different combinations. We suggest that CYP1A1 genotype might be associated with the reported reduced risk to papillary carcinomas among smokers.

Low expression of sodium iodide symporter identifies aggressive thyroid tumors

A decreased radioiodine uptake is frequently detected in differentiated thyroid carcinomas (DTC) and is associated with high recurrence rate and reduced survival. We investigated the correlation between NIS mRNA expression levels in the primary tumor and patient outcome using a quantitative real-time RT-PCR method. NIS expression was decreased in 17 DTC (21.04+/-39.66 pg Eq) compared to four autoimmune thyroid disease (180.51+/-92.63 pg Eq) and 14 normal tissues (75.71+/-66.98 pg Eq) (p<0.0001). The 17 thyroid differentiated carcinoma patients were submitted to surgery complemented by radioiodine ablation and had at least 24 months of follow-up, under levothyroxine continued suppressive therapy. According to their outcome, we could characterize a group of papillary carcinoma patients with aggressive carcinomas, whose NIS mRNA levels were markedly lower than a group with non-aggressive carcinomas (0.62+/-0.79 versus 54.87+/-53.79; p<0.005). We suggest that the quantification of NIS mRNA relative levels in the primary tumor may predict poor outcome.

Association between perceived lifetime risk of cardiovascular disease and calculated risk in a male population in Brazil.

Aim Cardiovascular disease is the major cause of morbidity and mortality across the world. Despite health campaigns to improve awareness of cardiovascular risk factors, there has been little improvement in cardiovascular mortality. In this study, we sought to examine the association between cardiovascular risk factors and people’s perception on cardiovascular risk. Methods This was an epidemiological, cross-sectional, descriptive, prospective study of Masonic men aged >40 years in Boa Vista, Brazil. Participants completed a health survey, which included three questions about perception of their stress level, overall health status, and risk of a heart attack. In addition, demographic and biological data were collected. Results A total of 101 Masonic men took part in the study; their mean age (± standard deviation) was 55.35±9.17 years and mean body mass index was 28.77±4.51 kg/m2. Answers to the lifestyle questionnaire suggested an overall healthy lifestyle, including good diet and moderate exercise, although despite this ~80% were classified as overweight or obese. The majority of participants felt that they had a low stress level (66.3%), good overall general health (63.4%), and were at low risk of having a heart attack (71.3%). Masons who were overweight were significantly more likely to perceive themselves to be at risk of a heart attack (P=0.025). Conclusion Despite over half of participants having a moderate to high risk of cardiovascular disease according to traditional risk factors, less than a third perceived themselves to be at high risk. Public health campaigns need to better communicate the significance of traditional cardiovascular risk in order to improve awareness of risk among the general population.

Leiomyoma – a rare benign tumor of the female urethra: a case report

IntroductionLeiomyoma in the urethra is a rare occurrence. These are rare benign mesenchymal tumors that arise from the smooth muscle of the urethra. Such tumors often appear in females during their reproductive age (from menarche to menopause); the mean age of their appearance is approximately 41 years.Case presentationWe report here a case of a 52-year-old White woman who presented with complaints of sporadic hematuria, dyspareunia, and feeling of nodulation in her vagina.ConclusionsHistopathological studies confirmed the urethral leiomyoma, and the surgery completely resolved the original symptoms. Although the average age of occurrence of such tumors in females is about 41 years, the present case involves an older woman of 52 years. Most importantly, the mass was located in the distal urethra, an uncommon site of presentation of leiomyoma in females.

No evidence for mutations in exons 1, 8 and 18 of the patched gene in sporadic skin lesions of Brazilian patients

There is strong evidence that the patched (PTCH) gene is a gene for susceptibility to the nevoid basal cell carcinoma syndrome. PTCH has also been shown to mutate in both familial and sporadic basal cell carcinomas. However, mutations of the gene seem to be rare in squamous cell carcinomas. In order to characterize the role of the gene in the broader spectrum of sporadic skin malignant and pre-malignant lesions, we performed a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis of genomic DNA extracted from 105 adult patients (46 females and 59 males). There were 66 patients with basal cell carcinomas, 30 with squamous cell carcinomas, 2 with malignant melanomas and 7 patients with precancerous lesions. Two tissue samples were collected from each patient, one from the central portion of the tumor and another from normal skin. Using primers that encompass the entire exon 1, exon 8 and exon 18, where most of the mutations have been detected, we were unable to demonstrate any band shift. Three samples suspected to present aberrant migrating bands were excised from the gel and sequenced directly. In addition, we sequenced 12 other cases, including tumors and corresponding normal samples. A wild-type sequence was found in all 15 cases. Although our results do not exclude the presence of clonal alterations of the PTCH gene in skin cancers or mutations in other exons that were not screened, the present data do not support the presence of frequent mutations reported for non-melanoma skin cancer of other populations.

Primary testicular mucinous cystadenoma: Case report and literature review

Testicular mucinous cystadenomas are rare in urological practice, and their histogenesis, course and management are debated. We report a primary testicular mucinous cystadenoma in a 54-year old male who presented with left testicular swelling and pain. He denied having a history of cryptorchidism, testicular trauma, infections, urinary complaints, or febrile illnesses. He did not have diabetes, but was on treatment for hypertension. The patient underwent a left inguinal radical orchiectomy, and histological examination of the resected tumour confirmed a primary testicular mucinous cystadenoma. The patient had an uneventful recovery, and is being followed up. Conclusively, urologists need to maintain a high index of suspicion of these tumours and their differentiation from metastatic tumours to ensure optimal therapeutic outcomes.

1729 N-ACETYLTRANSFERASE-2 GENE POLYMORPHISMS AND PROSTATE CANCER SUSCEPTIBILITY IN LATIN AMERICAN PATIENTS

We investigated the role of N-acetyltransferases (NAT) in prostate cancer (PCa) susceptibility. NAT are polymorphic in the population and metabolize important carcinogenic products directly involved in the tumor initiation process. This prospective case–control study utilized the polymerase chain reaction-based restriction fragment length polymorphism method and comprised a cohort of consecutive 478 individuals: 126 men with prostate cancer; 101 men with benign prostatic hyperplasia (BPH); and a control health population of 177 female and 74 male blood donors from the same region. NAT2 slow or fast acetylators genotypes were determined by the combination of four variant alleles. Lifetime occupational history, dietary patterns, cigarette smoking and other anamnestic data were obtained by interviews. We were not able to find any correlation among smoking, dietary patterns, parameters of tumor aggressiveness or patient outcome and any NAT2 genotypes or phenotypes considered in separate or in different combinations. However, there was an association between NAT2T481C (OR = 0.47; 95% CI = 0.26–0.84; P = 0.01) and NAT2A803G (OR = 0.57; 95% CI = 0.33–0.97; P = 0.04) polymorphisms and PCa protection. Conversely, the presence of NAT2G857A genotype increased the risk of PCa more than 3 times (OR = 3.57; 95% CI = 1.39–9.15; P = 0.005). Slow acetylator NAT2*7A and NAT2*6B genotypes occurred in 10.31% of PCa but in none of BPH patients (P = 0.0007). The control health population confirmed the results and allowed the exclusion of possible biases caused by gender influence on genotype inheritance and by the inclusion of not diagnosed prostate diseases patients among the control individuals. We suggest that the investigation of germline polymorphisms of NAT2 gene may be useful in the assessment of Latin American patients at risk of BPH and PCa.

Lack of mutation in exon 10 of p53 gene in thyroid tumors

: p53 es una proteina nuclear que tiene un rol impor-tante en la regulacion de la proliferacion celular y comanda cascadas de senalizacion para lareparacion de ADN y apoptosis. En muchos tipos de cancer, hay una alta frecuencia de muta-ciones de p53. Estas mutaciones tambien son muy prevalentes en el cancer indiferenciado detiroides, pero no se encuentran en tumores benignos y son infrecuentes en el cancer bien diferen-ciado. La mayor parte de las mutaciones se localizan en los exones 5 a 8 del gen. Recientementese ha descrito una mutacion de la linea germinal del exon 10 en el codon 337 del p53, en ninosbrasilenos con tumores suprarrenales.