Genome-Wide Association Analysis Of Proinflammatory Cytokines And Gene- Lifestyle Interaction For In

Considering the possibility of interaction of lifestyle factors with immune-related etiologic pathways to influence invasive breast cancer risk, researchers sought to further characterize the interrelated molecular genetic pathways. From the Women's Health Initiative Database for Genotypes and Phenotypes Study, they assessed 16,088 postmenopausal women, a population with high susceptibility to inflammation, obesity, and increased risk for breast cancer. With 21,784,812 common autosomal single-nucleotide polymorphisms (SNP), a genome-wide association (GWA) gene–environment interaction (G × E) analysis was carried out for proinflammatory cytokines [IL6 and C-reactive protein (CRP)] and their gene–lifestyle interactions in six independent GWA Studies. In women overall and stratified by obesity status (body mass index, waist circumference, and waist-to-hip ratio) and obesity-related lifestyle factors (exercise and high-fat diet), they identified association of 88 GWA SNPs in 10 loci with proinflammatory cytokines: 3 correlated with IL6 (1 index SNP in MAPK1 and 1 independent SNP in DEC1); 85 with CRP (3 index SNPs in CRPP1, CRP, RP11–419N10.5, HNF1A-AS1, HNF1A, and C1q2orf43; and two independent SNPs in APOE and APOC1). Of those, 27 in HNF1A-AS1, HNF1A, and C1q2orf43 exhibited significant correlation with raised risk for breast cancer. These findings may aid in better ascertaining the genetic correlations between pro-inflammation and cancer and in identifying intervention strategies for women who carry the risk genotypes, decreasing breast cancer risk.

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