Overexpression of heat-shock protein 47 impacts survival of patients with oral squamous cell carcinoma.

BACKGROUND: The expression of heat-shock protein 47 (HSP47) has been linked to collagen synthesis control and implicated in fibrotic disorders, but more recent studies have demonstrated its role in solid tumors. In this study, we explored the prognostic impact of HSP47 in oral squamous cell carcinomas (OSCC) and determined the in vitro effects of its loss-of-function on viability, proliferation, migration, invasion, and resistance to cisplatin of OSCC cells. METHODS: The HSP47 expression in tumor samples was assessed by immunohistochemistry in two independent cohorts totaling 339 patients with OSCC, and protein levels were associated with clinicopathological features and survival outcomes. The OSCC cell lines HSC3 and SCC9 were transduced with lentivirus expressing short hairpin RNA to stably silence HSP47 and used in assays to measure cellular viability, proliferation, migration, and invasion. RESULTS: HSP47 was overexpressed in OSCC samples, and its overexpression was significantly and independently associated with poor disease-specific survival and shortened disease-free survival in both OSCC cohorts. The knockdown of HSP47 showed no effects on cell viability or cisplatin sensitivity, but impaired significantly proliferation, migration, and invasion of OSCC cells, with stronger effects on SCC9 cells. CONCLUSION: Our results show a significant prognostic impact of HSP47 overexpression in OSCC and reveal that HSP47 inhibition impairs the proliferation, migration, and invasion of OSCC cells. HSP47 may represent a potential therapeutic target for OSCC.

Prognostic significance of the neural invasion in oral squamous cell carcinoma.

BACKGROUND: Although nerve involvement can predict recurrence and prognosis in oral squamous cell carcinomas, there still have controversies and limitations regarding the standardization for its detection. In this study, we explore the impact of neural invasion in oral squamous cell carcinomas prognosis, comparing intraneural invasion (tumor cells inside nerve structure) and perineural invasion (cells involving the nerve, but not invading its sheath). METHODS: Surgical slides stained with hematoxylin and eosin from 235 patients with oral squamous cell carcinomas were carefully verified for the presence of intraneural invasion and perineural invasion. The location in the tumor (intratumoral vs. peritumoral) and number of foci (unifocal or multifocal) were also explored. Survival analyses for cancer-specific survival and disease-free survival were performed with Cox proportional model. RESULTS: Neural invasion was identified in 74 cases, 64.9% displayed intraneural invasion and 35.1% displayed perineural invasion. Univariate analysis revealed a significantly poorer cancer-specific survival, but not disease-free survival, in patients with intraneural invasion, in contrast to cases with perineural invasion that did not achieve significant association with both cancer-specific survival and disease-free survival. Further analyses revealed that the location in the tumor and number of foci had little impact on discriminatory ability of intraneural invasion. Multivariate analysis confirmed that intraneural invasion is significantly and independently associated with poor cancer-specific survival (hazard ratio: 2.50, 95% CI: 1.31-3.79, p = 0.003). CONCLUSION: This study provides evidence that intraneural invasion, but not perineural invasion, is a relevant predictor of survival in patients with oral squamous cell carcinomas, suggesting that its association with other clinical and pathological prognostic factors should be consider in determining the optimal treatment protocol and prognosis of these patients.

Exploring the combination of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early-stage oral squamous cell carcinoma prognosis.

BACKGROUND: While the relevance of the World Health Organization histopathological grading system as a prognostic tool for oral squamous cell carcinoma has received many critics, other histopathological features such as tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding are displaying promising results. Here, we evaluated the prognostic impact of the incorporation of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding into World Health Organization histopathological grading for patients with oral squamous cell carcinoma. METHODS: A total of 95 patients with early-stage oral squamous cell carcinoma were enrolled in the study, and World Health Organization tumor grading, tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding were evaluated in surgical slides stained with hematoxylin and eosin. Survival analyses for cancer-specific survival and disease-free survival were performed using Cox regression models, and receiver operating characteristic curves were applied for assessment of the performance of the combinations. RESULTS: Tumor-stroma ratio (stroma-rich) was significantly and independently associated with both shortened cancer-specific survival and poor disease-free survival, individually and in combination with World Health Organization histopathological grading. The combination of tumor-stroma ratio with World Health Organization grading did not improve the discriminatory ability compared to tumor-stroma ratio alone. Although low tumor-infiltrating lymphocytes were associated with shortened cancer-specific survival, the association did not withstand multivariate analysis. However, in combination with World Health Organization grading, low tumor-infiltrating lymphocytes were independently associated with poor cancer-specific survival. The combination of tumor-infiltrating lymphocytes and World Health Organization histopathological grading displayed a better discrimination of poor cancer-specific survival than tumor-infiltrating lymphocytes alone, but not at a significant level. CONCLUSION: Our findings support tumor-stroma ratio as a potential prognostic marker for patients with oral squamous cell carcinoma, and the incorporation of tumor-infiltrating lymphocytes into the World Health Organization grading system improves the prognostic ability of the tumor grading alone.

Stress induced phosphoprotein 1 overexpression controls proliferation, migration and invasion and is associated with poor survival in oral squamous cell carcinoma.

Objective: Although there have been remarkable achievements in the molecular landscape of oral squamous cell carcinoma (OSCC) in recent years, bringing advances in the understanding of its pathogenesis, development and progression, little has been applied in the prognosis and choosing the optimal treatment. In this study, we explored the influence of the stress induced phosphoprotein 1 (STIP1), which is frequently reported to be highly expressed in many cancers, in OSCCs. Methods: STIP1 expression was assessed in the TCGA database and in two independent cohorts by immunohistochemistry. Knockdown strategy was applied in OSCC cell lines to determine the impact of STIP1 on viability, proliferation, migration and invasion. The zebrafish model was applied for studying tumor formation and metastasis in vivo. The association of STIP1 and miR-218-5p was explored by bioinformatics and mimics transfection. Results: STIP1 was highly expressed in OSCCs and significantly associated with shortened survival and higher risk of recurrence. STIP1 down-regulation decreased proliferation, migration and invasion of tumor cells, and reduced the number of metastases in the Zebrafish model. STIP1 and miR-218-5p were inversely expressed, and the transfection of miR-218-5p mimics into OSCC cells decreased STIP1 levels as well as proliferation, migration and invasion. Conclusion: Our findings show that STIP1 overexpression, which is inversely associated with miR-218-5p levels, contributes to OSCC aggressiveness by controlling proliferation, migration and invasion and is a determinant of poor prognosis.

Trophoblast cell surface antigen 2 expression predicts outcome in oral squamous cell carcinomas.

BACKGROUND: Trophoblast cell surface antigen 2 (TROP2) has unclear clinical role in oral squamous cell carcinomas (OSCC). Here, we investigated the association of TROP2 immunoexpression with clinicopathological parameters and survival of OSCC patients. SUBJECTS AND METHODS: Cancer-specific survival (CSS) and disease-free survival (DFS) were assessed in a cohort composed of 266 OSCC. An independent cohort with 88 OSCC samples matched with the normal oral tissue, as well as 17 metastatic lymph nodes, was used for validation. RESULTS: Multivariate analysis showed TROP2 as an independent marker of favorable prognosis for both CSS (HR: 0.60, 95% CI: 0.40-0.90, p = .01) and DFS (HR: 0.57, 95% CI: 0.36-0.89, p = .01). Furthermore, TROP2 protein expression was significantly higher in morphologically normal tissues compared to primary tumors (p < .0001) and lymph node metastases (p = .001), and it was significantly associated with CSS (HR: 0.26, 95% CI: 0.09-0.74, p = .008) in the validation cohort. A pooled mRNA analysis performed on the Oncomine™ database confirmed the underexpression in OSCC compared with normal tissues (p = .014). CONCLUSIONS: In summary, our results point to a favorable prognostic significance of TROP2 overexpression in a large cohort of oral cancer patients, suggesting it as an attractive clinical marker.

Eukaryotic translation elongation factor 1δ, N-terminal propeptide of type I collagen and cancer-associated fibroblasts are prognostic markers of oral squamous cell carcinoma patients.

OBJECTIVE: Identifying markers that influence oral squamous cell carcinoma (OSCC) prognosis is a fundamental strategy to improve the overall survival of patients. Markers such as eukaryotic translation elongation factor 1δ (EEF1D), fascin, N-terminal propeptide of type I collagen (PINP), and cancer-associated fibroblasts (CAFs) have been noticed in OSCCs and their levels are closely related to the prognosis of tumors. Our aim was to confirm the role of those markers in OSCC prognosis. STUDY DESIGN: Immunohistochemistry was performed in 90 OSCC specimens. The associations between clinicopathologic features and expression of markers were assessed by χ2 test. Kaplan-Meier curves and univariate and multivariate Cox regression models were used for survival analysis. Markers were analyzed individually and in combination. RESULTS: High expression of EEF1D (P = .017) and PINP (P = .02) and abundant density of CAFs in tumor stroma (P = .005) predicted significantly poor survival in OSCC patients. Multivariate analysis revealed that all 3 parameters are individually independent prognostic factors of OSCC patients, and their combination improved the discrimination of patients at high risk for poor survival. CONCLUSIONS: Our results suggested that the expression of EEF1D and PINP and the density of CAFs might influence the survival of patients with OSCC.

Two rare cases of oral metastasis arising from lung adenocarcinoma and esophageal carcinoma.

Metastasis to the oral cavity are rare, representing only 1% of all oral malignancies, and originate from various sites such as the breast, prostate, lung and kidney. Clinically, they can simulate reactive and inflammatory lesions common in the oral cavity, and the clinical and microscopic diagnosis of these metastasis is a challenge. In this article, we report two new cases of esophageal and lung metastasis to oral tissues, highlighting their clinical characteristics and the process of diagnostic elucidation. We emphasize the importance for clinicians to consider the possibility of metastatic lesions in the oral cavity in patients previously diagnosed with malignant lesions in distant tissues and organs. Key words:Diagnosis, esophageal squamous cell carcinoma, adenocarcinoma of lung, oral cavity, metastasis.

Prognostic value of immunoexpression of CCR4, CCR5, CCR7 and CXCR4 in squamous cell carcinoma of tongue and floor of the mouth

Background: Diverse studies have evidenced that chemokines can play a critical role in pathogenesis of oral squamous cell carcinoma (SCC). The main chemokines involved in oral carcinogenesis, tumor invasion and metastasis are CCR4, CCR5, CCR7 and CXCR4, and our aim was to evaluate the prognostic value of the immunoexpression of these chemokines in SCC of tongue and floor of the mouth. Material and Methods: A retrospective descriptive study of the immunohistochemical expression of CCR4, CCR5, CCR7 and CXCR4 in paraffin-embedded samples of 124 patients with SCC of the tongue and floor of the mouth was performed, considering 98 cases from Brazil and 26 cases from Chile. Associations between variables were analyzed using chi-square test. Survival curves were performed using the Kaplan-Meier method and compared with long-rank test. For multivariate survival analysis, the Cox hazard model was established. The level of significance established was p ≤ 0.05. Results: The statistical analysis showed that samples with well or moderate WHO model differentiation (p = 0.001) and a high expression of CCR5 (p = 0.05) were significantly associated with a higher disease specific survival, which were also observed in Cox ́s multivariate analysis (p = 0.01). A higher expression of CCR7 (p = 0.01) interfered significantly in disease-free survival in univariate analysis and in Cox ́s multivariate analysis (p = 0.05). Conclusions: These results support additional evidence, showing that chemokine receptors CCR5 and CCR7 are helpful as biomarkers of poor prognosis in patients with SCC of the tongue and floor of the mouth

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Variable expressivity and novel PTEN mutations in Cowden syndrome.

Cowden syndrome (CS) is a phosphatase and tensin homolog gene (PTEN)-associated condition characterized by multiple mucocutaneous hamartomas and an increased risk of malignancies. We reported an isolated case and another of several individuals in one family affected by CS. The isolated case showed typical features, including fibrocystic breast disease, benign thyroid nodules, and multiple papillomatous lesions in the face and oral cavity, and the cause was a novel nonsense mutation-guanine (G) to thymine (T) transition at position 940 (c.940 G>T)-in PTEN. In the family, the proband showed erythema nodosum, duodenal ulcer, intestinal polyps, cervical lipoma, renal cysts, and glaucoma, whereas multiple members of her family were found to have intestinal polyps, and a sister had been diagnosed with breast cancer at early age. An intronic mutation-T>G transition at the +32 position of intron 8 (c.1026+32 T>G)-was found in this family, with in silico analysis revealing the creation of a new donor splice site. This study confirmed the involvement of PTEN in CS and the variable clinical expressivity of disease.

Oral Manifestation of Lymphomatoid Granulomatosis.

Lymphomatoid granulomatosis (LYG) is a rare B-cell lymphoproliferative disorder driven by Esptein-Barr virus (EBV) that most commonly affects the lungs, although extra pulmonary sites like the central nervous system, skin, liver and kidney can also be involved. It is microscopically characterized by an angiocentric and angiodestructive growth pattern, predominantly composed by small T-cells, although a smaller population of atypical large B-cells is considered the true neoplastic component. Oral cavity involvement of LYG has rarely been described and the diagnosis of this neoplasm is very difficult. The aim of this report is to present a rare case of LYG affecting an 86-year-old female patient that was diagnosed due to an extensive, ulcerated and painful oral lesion affecting the hard palate. Detailed microscopic evaluation together with a large immunohistochemical study were necessary to achieve the correct diagnosis of LYG.

A challenging diagnosis: Case report of oral metastasis from gastric adenocarcinoma mimicking pyogenic granuloma.

RATIONALE: Oral metastases occur more commonly in bone, but can also manifest in soft tissues and eventually resemble a reactive lesion. Few cases of oral metastases mimicking reactive lesions in soft tissues have been reported to date. PATIENT CONCERNS: We report a metastasis of gastric carcinoma (GC) to the oral mucosa without bone involvement in a 43 yom clinically and microscopically mimicking a reactive lesion. The patient related that the lesion had 1 month of evolution, and the ulcerated area suggested the lesion was related to trauma. DIAGNOSES: The histopathological examination of the lesion revealed an exuberant granulation tissue with few neoplastic cells, and the initial diagnosis of pyogenic granuloma was considered. In a second analysis, clusters of clear cells morphologically similar to degenerating mucous cells or macrophages, positive for Cytokeratin (CK)-20, and CDX2 were found. At the moment, it was confirmed the presence of a primary GC in the patient. INTERVENTIONS: A palliative radiotherapy/chemotherapy was started. OUTCOMES: However, the patient died 3 months after the diagnosis of oral metastasis. LESSONS: This report highlights the importance of careful clinical and microscopic examinations in cases of oral metastasis that may mimic a reactive lesion.

Metachronous ameloblastic fibro-odontoma and dentigerous cyst in the posterior mandible.

An ameloblastic fibro-odontoma (AFO) is a rare mixed odontogenic tumor with histologic features of an ameloblastic fibroma in conjunction with the presence of dentin and enamel. It usually appears as a well-circumscribed radiolucency with radiopaque foci and slow growth and is commonly seen in children and young adults. A 13-year-old boy presented with an asymptomatic swelling in the posterior right region of the mandible and the right ascending ramus. The clinical, imaging, and histopathologic findings confirmed the diagnosis of an AFO. After 8 months, a radiolucent lesion involving the unerupted mandibular left third molar was observed; a final diagnosis of a dentigerous cyst (DC) was established for this lesion. Although coincidental events, metachronous odontogenic lesions suggest a possible common genetic origin, since both can be caused by related cellular signaling pathways. Complete enucleation is recommended for both AFOs and DCs; rates of recurrence are low.

Association Between Hand Digit Ratio (2D:4D) and Nonsyndromic Orofacial Clefts.

OBJECTIVES: Digit ratio (2D:4D) has been considered to be a marker in studies evaluating an individual's susceptibility to diseases, especially those diseases that show sex differences in their occurrence. We aimed to assess whether 2D:4D ratios are associated with nonsyndromic cleft lip and/or palate (NSCL/P) and verify the existence of a specific pattern of 2D:4D ratio in individuals affected by orofacial clefts. DESIGN: This was a case-control study. METHODS: Digital measurements of index and ring finger lengths of both hands of patients with NSCL/P (n = 54) and age- and gender-matched controls (n = 54) were obtained using a digital vernier caliper. Mean ratios between the second and fourth digits were compared. Data were analyzed by Student's t test and Mann-Whitney test with a significance level of 5%. RESULTS: No significant difference was found between the mean digit ratios of the right and left hands between the groups for any analysis (P > .05), neither for the whole sample nor for the distributions by type of cleft and by gender. CONCLUSIONS: Although the development of the fingers and the occurrence of NSCL/P can be regulated by the actions of similar genes, our results are not consistent with an association between 2D:4D ratio and this craniofacial deformity. This suggests that intrauterine exposure to fetal androgens, assessed using this marker, is similar between patients with NSCL/P and healthy individuals. We highlight the need for further studies in populations with different ancestries.

Maternal and congenital syphilis, underreported and difficult to control. / Sífilis materna e congênita, subnotificação e difícil controle.

OBJECTIVE: To identify and to describe cases of congenital and maternal syphilis reported and not reported in a Brazilian medium-sized city. METHODS: This is a descriptive and retrospective study, which evaluated 214 medical records of pregnant women and newborns. It began with the identification of epidemiological notification records, followed by active search in maternity evaluating all records that did show positive nontreponemal serology and records of the reference service in infectious diseases in Montes Claros, Minas Gerais, from 2007 to 2013. The case definitions followed the Ministry of Health recommendations in Brazil and the variables were described using absolute and relative frequencies. This study was approved by the Ethics in Research Committee (University State of Montes Claros). RESULTS: Of the 214 medical records, we identified 93 cases of maternal syphilis and 54 cases of congenital. The women studied were predominantly mulatto, with Secundary/Higher, aged between 21 and 30 years and single marital status. Considering the prenatal care of pregnant women with syphilis, it was observed predominance of late diagnosis, after parturition or curettage, and all of their treatments were considered inadequate according the Ministry of Health. The newborns of pregnant women with syphilis, most were not referenced for pediatric follow-up. Only 6.5% of syphilis in pregnant women was notified, and in congenital syphilis, 24.1%. CONCLUSION: Persisting vertical transmission, there are signs that the quality of prenatal and neonatal care should be restructured.

Sífilis materna e congênita, subnotificação e difícil controle / Maternal and congenital syphilis, underreported and difficult to control

RESUMO: Objetivo: Identificar e descrever casos de sífilis congênita e materna notificados e não notificados em uma cidade brasileira de médio porte. Métodos: Trata-se de estudo descritivo e retrospectivo que avaliou 214 prontuários de gestantes e recém-nascidos (RNs). Iniciou-se com identificação das fichas de notificação epidemiológica, seguida de busca ativa nas maternidades, avaliando-se todos os prontuários que apresentavam sorologia não treponêmica positiva e prontuários do serviço de referência em infectologia, na cidade de Montes Claros, Minas Gerais, no período de 2007 a 2013. As definições de casos seguiram as recomendações do Ministério da Saúde (MS) no Brasil e as variáveis foram descritas utilizando-se frequências absoluta e relativa. Estudo aprovado pelo Comitê de Ética em Pesquisa (Universidade Estadual de Montes Claros). Resultados: De 214 prontuários avaliados, foram identificados 93 casos de sífilis materna e 54 casos de sífilis congênita. As gestantes analisadas foram, predominantemente, de cor parda, apresentando ensino médio/superior, com faixa etária entre 21 e 30 anos e estado civil solteira. Considerando acompanhamento pré-natal das gestantes com sífilis, observou-se predomínio do diagnóstico tardio, após o parto ou a curetagem; a totalidade dos respectivos tratamentos foi considerada inadequada, segundo o MS. Dos RNs de gestantes com sífilis, a maioria não foi referenciada para acompanhamento pediátrico. Apenas 6,5% dos casos de sífilis em gestantes foram notificados; em relação à forma congênita, esse valor foi de 24,1%. Conclusão: Persistindo a transmissão vertical, verificam-se sinais de que a qualidade da atenção pré-natal e neonatal deve ser reestruturada.

ABSTRACT: Objective: To identify and to describe cases of congenital and maternal syphilis reported and not reported in a Brazilian medium-sized city. Methods: This is a descriptive and retrospective study, which evaluated 214 medical records of pregnant women and newborns. It began with the identification of epidemiological notification records, followed by active search in maternity evaluating all records that did show positive nontreponemal serology and records of the reference service in infectious diseases in Montes Claros, Minas Gerais, from 2007 to 2013. The case definitions followed the Ministry of Health recommendations in Brazil and the variables were described using absolute and relative frequencies. This study was approved by the Ethics in Research Committee (University State of Montes Claros). Results: Of the 214 medical records, we identified 93 cases of maternal syphilis and 54 cases of congenital. The women studied were predominantly mulatto, with Secundary/Higher, aged between 21 and 30 years and single marital status. Considering the prenatal care of pregnant women with syphilis, it was observed predominance of late diagnosis, after parturition or curettage, and all of their treatments were considered inadequate according the Ministry of Health. The newborns of pregnant women with syphilis, most were not referenced for pediatric follow-up. Only 6.5% of syphilis in pregnant women was notified, and in congenital syphilis, 24.1%. Conclusion: Persisting vertical transmission, there are signs that the quality of prenatal and neonatal care should be restructured.

Prevalence of depressive symptoms in patients with cleft lip and palate / Prevalência de sintomas depressivos em pacientes com fissuras labiopalatinas

INTRODUCTION: Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. OBJECTIVE: To evaluate the prevalence of depressive symptoms in children and adolescents with nonsyndromic cleft lip and/or palate (nsCL/P). METHODS: We conducted an observational, case-control study, with a case study group composed of 61 patients with nsCL/P, aged 7-17 years, and a control group of 61clinically normal patients. Both groups were selected at the same institution. RESULTS: Depressive symptoms were observed in the case group (nsCL/P), but there were no statistically significant differences compared to the control group. No association was found between the two groups (case and control) in relation to sociodemographic variables: gender, age and education. CONCLUSIONS: This study identified the prevalence of depressive symptoms in children and adolescents with nsCL/P from a localized geographic population, although the results were not statistically significant when compared to the control group, not justifying the use of CDI (Child Depression Inventory) as a screening instrument for depressive symptoms in the examined population. .

INTRODUÇÃO: Fissuras labiais e/ou palatinas (FL/Ps) representam as anomalias craniofaciais mais comuns. OBJETIVOS: Avaliar a prevalência de sintomas depressivos em crianças e adolescentes não sindrômicos com FL/P (FL/PNS). MÉTODO: Foi realizado um estudo observacional de caso-controle com uma amostra populacional de conveniência, com um grupo caso (61 pacientes com FL/PNS, tendo idades entre 7 a 17 anos) e um grupo controle (61 pacientes clinicamente normais). Ambos os grupos foram selecionados na mesma Instituição. RESULTADOS: Sintomas depressivos foram observados no grupo caso (FL/PNS), mas não houve diferenças estatisticamente significantes quando comparado com o grupo controle. Não foi encontrada associação entre os dois grupos (caso e controle) em relação às variáveis sociodemográficas: gênero, idade e educação. CONCLUSÕES: Este estudo observou a prevalência de sintomas depressivos em crianças e adolescentes com FL/PNS de uma população geográfica localizada, embora os resultados não tenham sido estatisticamente significantes quando comparado com o grupo controle, não justificando assim a utilização de instrumentos rastreadores de sintomas depressivos na população analisada. .

Prevalence of depressive symptoms in patients with cleft lip and palate.

INTRODUCTION: Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. OBJECTIVE: To evaluate the prevalence of depressive symptoms in children and adolescents with nonsyndromic cleft lip and/or palate (nsCL/P). METHODS: We conducted an observational, case-control study, with a case study group composed of 61 patients with nsCL/P, aged 7-17 years, and a control group of 61 clinically normal patients. Both groups were selected at the same institution. RESULTS: Depressive symptoms were observed in the case group (nsCL/P), but there were no statistically significant differences compared to the control group. No association was found between the two groups (case and control) in relation to sociodemographic variables: gender, age and education. CONCLUSIONS: This study identified the prevalence of depressive symptoms in children and adolescents with nsCL/P from a localized geographic population, although the results were not statistically significant when compared to the control group, not justifying the use of CDI (Child Depression Inventory) as a screening instrument for depressive symptoms in the examined population.

Contribution of polymorphisms in genes associated with craniofacial development to the risk of nonsyndromic cleft lip and/or palate in the Brazilian population

Background and Objective: Nonsyndromic cleft lip and/or palate (NSCL/P) is a complex disease associated with both genetic and environmental factors. One strategy for identifying of possible NSCL/P genetic causes is to evaluate polymorphic variants in genes involved in the craniofacial development. Design: We carried out a case-control analysis of 13 single nucleotide polymorphisms in 9 genes related to craniofacial development, including TBX1, PVRL1, MID1, RUNX2, TP63, TGFâ3, MSX1, MYH9 and JAG2, in 367patients with NSCL/P and 413 unaffected controls from Brazil to determine their association with NSCL/P. Results: Four out of 13 polymorphisms (rs28649236 and rs4819522 of TBX1, rs7940667 of PVRL1 and rs1057744of JAG2) were presented in our population. Comparisons of allele and genotype frequencies revealed that the Gvariant allele and the AG/GG genotypes of TBX1 rs28649236 occurred in a frequency significantly higher in controls than in the NSCL/P group (OR: 0.41; 95% CI: 0.25-0.67; p=0.0002). The frequencies of rs4819522, rs7940667and rs1057744 minor alleles and genotypes were similar between control and NSCL/P group, without significant differences. No significant associations among cleft types and polymorphisms were observed. Conclusion: The study suggests for the first time evidences to an association of the G allele of TBX1 rs28649236polymorphism and NSCL/P (AU)