RESUMEN
DNA repair gene polymorphisms have been implicated as susceptibility factors in cancer development. It is possible that DNA repair polymorphisms may also influence the risk of gene mutation. Polymorphisms in the DNA repair gene XRCC1 have been indicated to have a contributive role in DNA adduct formation and an increased risk of cancer development. 300 head and neck cancer patients and 150 controls were included in this study. PCR-single-strand conformation polymorphism and DNA sequencing were used to analyze the whole exonic region of XRCC1 in head and neck cancer patients. Sequence analysis revealed two missense and two silent mutations in our study. Frequency of silent mutations; Pro206Pro (rs915927) and Gln632Gln (rs3547) was calculated as 0.16 (16 %) and 0.30 (30 %) respectively. Whereas, the frequency of missense mutations; Arg399Gln (rs25487) and Tyr576Asn (rs2307177) was calculated as 0.27 (27 %) and 0.28 (28 %) respectively. In our study, incidence of these mutations was found higher in larynx cancer (p < 0.005) as compared to oral cavity and pharynx cancer. Our finding suggests that the polymorphic XRCC1 gene may contribute to risk of developing head and neck cancer. To our knowledge, this is the first report that XRCC1 is associated with increased risk of head and neck cancer in a Pakistani population.
Asunto(s)
Proteínas de Unión al ADN/genética , Neoplasias de Cabeza y Cuello/genética , Adulto , Pueblo Asiatico/genética , Reparación del ADN , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Masculino , Mutación Missense , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
Spleen tyrosine kinase (Syk) is an intracellular receptor protein kinase involved in cell proliferation, differentiation and phagocytosis. Syk expression has been reported in cell lines of epithelial origin. The strong expression of Syk in mammary gland prompted research into its potential role in mammary carcinogenesis. Fresh Biopsy samples were collected from different hospitals of Pakistan. Single stranded conformational polymorphism and Semi quantitative reverse transcriptase polymerase chain reaction was used to investigate somatic mutations and expression alterations in twenty five breast cancer tumor tissues along with their adjacent normal control tissue. Statistical analysis was performed to explore Syk association with breast cancer risk. In the present study, DNA from tumor tissue was analyzed and mutations in the coding sequence and intronic sequence spanning the exonic region of the Syk gene were identified. Sequence analysis revealed two missense: g61096G>A, g65967G>A, one frame shift: g87413insA and one silent mutation g42841G>A in exonic region while nucleotide variations were also observed in intronic region including one splice site mutation. These mutations in Syk are first time being reported in breast cancer. In addition, this study also revealed that Syk mRNA expression was markedly reduced in tissues of breast cancer compared to their adjacent normal control tissue.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/genética , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas Tirosina Quinasas/biosíntesis , Proteínas Tirosina Quinasas/genética , Secuencia de Bases , Neoplasias de la Mama/patología , Análisis Mutacional de ADN , Femenino , Humanos , Datos de Secuencia Molecular , Polimorfismo Conformacional Retorcido-Simple , ARN Mensajero/análisis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Quinasa SykRESUMEN
OGG1 (The human 8-oxoguanine glycosylase 1) is the primary enzyme in BER (base excision repair) pathway, responsible for the excision of 7, 8-dihydro-8-oxoguanine (8-oxoG), a mutagenic base byproduct that occurs as a result of exposure to reactive oxygen species. OGG1 gene is highly polymorphic among humans and is mutated in cancer cells. In this case control study, all exons of OGG1 gene and its exon/intron boundaries were amplified in 210 laryngeal cancer cases and 210 matched controls and then analyzed by single stranded conformational polymorphism. Amplified products showing altered mobility patterns were sequenced and analyzed. Two silent (Gln718Gln, His699-700His) and three missense (Ala597, Thr608-610Pro and Glu707Lys) mutations were observed in exon 2. In addition to this one missense mutation (1578G > A) was also observed in 3'UTR region. We found a significant association between OGG1 mutations and laryngeal cancer and observed that His699-His700, silent mutation exhibited an enhanced risk of ~9.0 folds (OR = 9.07, 95 % CI = 4.73-17.39) and 1578G > A, missense mutation ~0.4 folds (OR = 0.37, 95 % CI = 0.15-0.90). Furthermore, a positive association of OGG1 mutations with smoking was observed in laryngeal cancer cases when compared to controls. Heavy smokers have higher incidence of OGG1 mutations when compared to light smokers in present study. Our results demonstrate that OGG1 mutations are associated with an increased risk of laryngeal cancer. OGG1 mutations were found to accumulate more of 8-OHdG in smokers, which may serve as a biomarker for early diagnosis of laryngeal cancer.