BJOG An International Journal of Obstetrics & Gynaecology · 2009 · 36 citations · 26 references
Life SciencesGeneticsImmunologyEpidemiologyGenetic EpidemiologyImmunogeneticsCancer EtiologyCervical CancerCervical Intraepithelial NeoplasiaCytokine Gene PolymorphismGenetic Risk AssessmentGenetic Risk FactorsCancer Risk AssociationCervical Cancer Risk AssessmentDisease Susceptibility AssociationInterferon Gene PolymorphismsInterferon Gene VariantsPro-inflammatory Cytokine ExpressionSingle-nucleotide Polymorphism AnalysisSingle-nucleotide Polymorphism Variation
OBJECTIVE: Interferon gamma (IFN-gamma) is a pro-inflammatory cytokine playing a pivotal role in both innate and adaptive immune responses. A single nucleotide polymorphism located in the first intron of the human IFN-gamma gene can influence the secretion of cytokine. Therefore, we aimed to investigate the association of IFN-gamma T/A gene polymorphism with the risk of cervical cancer. DESIGN: Case-control study. SETTING: Uttar Pradesh State in India. SAMPLE: Two hundred cases with histologically proven cancer of the cervix and healthy controls (n = 230), age and ethnicity matched were recruited in this study. METHODS: Genotyping was performed for bi-allelic +874 (T/A) polymorphism of IFN-gamma by amplification refractory mutation system method. MAIN OUTCOME MEASURES: Low producer IFN-gamma +874 AA genotype was associated with high risk for cervical cancer, which further modulated the increased risk in tobacco users. RESULTS: IFN-gamma AA genotype which is low producer of IFN-gamma was associated with increased risk of cervical cancer (OR = 2.43, P = 0.003). Allele A was at 1.54-fold increased risk of cervical cancer (OR=1.54, P = 0.002). The AA genotype showed statistically significant risk with high stage (III + IV) of cervical cancer (OR = 4.99, P = 0.001). In tobacco users, AA genotype showed significantly increased susceptibility to cervical cancer (OR = 5.08, P = 0.010). CONCLUSION: Variation in IFN-gamma +874 AA genotype because of ethnicity in north-Indian population may represent an important susceptibility biomarker for cervical cancer risk as well as other diseases and should be explored further.
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A single nucleotide polymorphism in the first intron of the human IFN-γ gene:
Vera Pravica, Chris Perrey, Adam Stevens et al. · Human Immunology · 2000 · 615 citations
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