Protective association exhibited by the single nucleotide polymorphism (SNP) rs1052133 in the gene human 8-oxoguanine DNA glycosylase (hOGG1) with the risk of squamous cell carcinomas of the head & neck (SCCHN) among north Indians.

Background & objectives: Imbalances in compactly regulated DNA repair pathways in the form of single nucleotide polymorphisms (SNPs) within vital DNA repair genes may result in insufficient DNA repair and increase in DNA breaks thus rendering the human system vulnerable to the debilitatory effects of grave diseases like cancers. The present study involves investigation of association of the non-synonymous SNP rs1052133 (C8069G/Ser326Cys) located in the exonic region of the gene human 8-oxoguanine DNA glycosylase (hOGG1) with the risk of squamous cell carcinomas of the head and neck (SCCHN). Methods: Case-control based genetic association study was performed among 575 (250 SCCHN cases and 325 normal healthy controls) sub-population cluster-matched (Indo-Europeans linguistic subgroup + Caucasoid morphological subtype) samples from the north Indian States of Uttar Pradesh and Uttarakhand using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing analysis. Results: Our results demonstrated statistically significant protective association for the heterozygous CG [Odds Ratio (OR) 0.6587, 95% Confidence Interval (CI) 0.4615 to 0.9402, P=0.0238], homozygous mutant GG (OR 0.2570, 95% CI 0.1070 to 0.6175, P=0.0013) and combined mutant CG + GG (OR 0.6057, 95% CI 0.4272 to 0.8586, P=0.0059) genotypes. Interpretation & conclusions: The results indicate that the polymorphism rs1052133 is strongly associated with SCCHN susceptibility and the mutant (G) allele might be a protective factor for SCCHN among north Indian subpopulations.

Prognostic significance of MMP2 and MMP9 functional promoter single nucleotide polymorphisms in head and neck squamous cell carcinoma

Matrix metalloproteinases comprise a family of enzyme that is able to degrade components of extra cellular matrix. There are single nucleotide polymorphisms in the promoter regions of several genes with ability to influence cancer susceptibility. The aim of this study was to analyses association between MMP2 and MMP9 promoter polymorphisms and head and neck squamous cell carcinoma occurrence and progression. A case- control study was performed including 80 head and neck squamous cell carcinoma patients and healthy controls for MMP2 and 86 head and neck squamous cell carcinoma patients and 72 healthy controls for MMAP9. Blood samples were genotyped for MMP2 and MMP9 using polymerization chain reaction-restriction fragment length polymorphism method [PCR-RFLP]. Statistical analysis was performed using SPSS 12.0 software. Our results showed that distribution of MMP2 genotype between controls and patients was significantly different [Chi[2] = 10.3, P= 0.005]. Comparison between CC genotype in HNSCC patients and controls showed that C allele modified the risk of HNSCC progression [OR= 2.6, 95% CI, 1.0046-6.729]. The MMP9 genotype distribution among HNSCC patients was significantly different [Chi[2] = 14.56, P= 0.0007]. The frequency of TT genotype in HNSCC patients was different from healthy controls and was more common genotype in HNSCC cases [OR= 2.18, 95% CI, 0.7052-6.7854]. Our results suggested an association of the MMP2 and MMP9SNP with the development of HNSCC. Also, our results showed that MMP, MMP9 genotypes and smoking were related to HNSCC progression

Perfil genômico do carcinoma de células escamosas de laringe e seu fronte de invasão / Genomic profiling of squamous cell carcinoma of the larynx and its invasive front

Câncer de laringe ocorre em 25 dos carcinomas de cabeça e pescoço e compreende 2 de todas as doenças malignas. É comum o aparecimento de segundos tumores primários e, aproximadamente, 5 dos pacientes apresentam cânceres sincrônicos. Há várias evidências indicando que a população celular presente no fronte de invasão possui características moleculares diferentes das áreas tumorais superficiais, tornando esta região importante para avaliação prognóstica. Neste estudo foram investigadas por CGH cromossômico de alta resolução (HR-CGH) as alterações genômicas na área superficial e no fronte de invasão de carcinomas de laringe e selecionadas regiões específicas para serem avaliadas por outras metodologias para a confirmação dos resultados. O componente superficial e o fronte de invasão de 33 carcinomas de laringe fixados em formalina e em blocos de parafina foram avaliados por HR-CGH. Foram detectadas alterações comuns aos dois componentes assim como alterações exclusivas a cada um deles. Adicionalmente, foi investigada e confirmada a expressão aumentada da proteína ciclina D1 o gene CCND1 esta mapeada em 11q13) por análise de expressão em plataformas de microarranjos de tecidos contendo as áreas do tumor e do fronte de invasão. Foi realizada também a análise de marcadores polimórficos de microssatélites mapeados em 3q e 18q em um grupo independente de 33 amostras (DNA tumoral e do sangue periférico) cujos resultados confirmaram as perdas encontradas nestas regiões cromossômicas. A expressão do gene CTTN (mapeada em 11q13) e de sua proteína foram avaliadas e revelaram que os altos níveis de expressão proteica foram correlacionados com invasão perineural nas células do fronte de invasão, sugerindo que esta área pode ser considerada como ferramenta prognóstica em carcinomas de laringe. Foram investigados os ganhos detectados em 2q24...

CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study

CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A->G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A->G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95 percent CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95 percent CI = 0.70-2.79) with OSCC.

Molecular aspects of esophageal squamous cell carcinoma carcinogenesis

RACIONAL: O desenvolvimento do câncer de esôfago humano é um processo progressivo de diversas etapas. Um indicador precoce deste processo é o aumento na proliferação das células epiteliais esofágicas, incluindo alterações morfológicas, como hiperplasia das células basais, displasia, carcinoma in situ e carcinoma avançado de células escamosas do esôfago. Ao nível celular, o processo de carcinogênese está relacionado com alterações no controle de proliferação celular, diferenciação e morte celular programada (apoptose). A maioria das células tumorais contém alterações genéticas que se relacionam com o controle desses processos, incluindo fatores de transcrição e proteínas relacionadas à apoptose. OBJETIVO: Neste artigo de revisão apresenta-se o conhecimento acerca do perfil genético deste subgrupo de tumor do esôfago, focando-se no potencial desenvolvimento de novas ferramentas para o tratamento clínico do carcinoma avançado de células escamosas do esôfago. CONCLUSÕES: O avanço no campo da biologia molecular tem permitido um maior conhecimento do processo de carcinogênese do esôfago, que deve resultar em benefícios aos pacientes com câncer. Desta forma, espera-se que um melhor entendimento das alterações moleculares durante a carcinogênese aumente o controle e a prevenção ao câncer e também possa levar ao tratamento melhorado da doença.