Abstract
The interferon-lambda (IFNL) cytokines have been shown to be important in HCV infection with SNPs in the IFNL3 gene associated with both natural and treatment induced viral clearance. We have recently shown that rs1299860 (an IFNL3 associated SNP) and an NK cell gene, KIR2DS3, synergised to increase the odds of chronic infection in a homogenous cohort of Irish women infected with HCV. To characterise a biological basis for the genetic synergy, we investigated for any evidence that IFNL cytokines regulate NK cell functions. Using a range of functional responses, we did not find any evidence of NK cell activation by IFNL3, IFNL1 or IFNL2 cytokines. Similar results were found using human and murine NK cells. In addition, and in contrast to our preliminary study, we did not find any evidence that IFNL cytokines inhibited NK cell cytokine production; thus, the biological basis for the genetic synergy remains to be discovered.
Highlights
Breast cancer is the most common female cancer worldwide
The results from this study will provide valuable information regarding the role of modifiable lifestyle risk factors for breast cancer in women with a deleterious mutation in the BRCA gene
The study will attempt to identify potential blood biomarkers which may be predictive of breast cancer occurrence
Summary
Breast cancer is the most common female cancer worldwide. The lifetime risk of a woman being diagnosed with breast cancer is approximately 12.5%. In recent years there has been increased penetrance of BRCA1 and BRCA2 associated breast cancer, prompting investigation into the role of modifiable risk factors in this group. Previous investigations into this topic have relied on participants recalling lifetime weight changes and subjective methods of recording physical activity. While most breast cancers are sporadic in nature, approximately 510% are attributed to genetics, arising from autosomal dominant mutations in specific cancer genes, the strongest of which are the two breast cancer susceptibility genes, BRCA1 or BRCA2 Women who carry these mutations have up to an 80% risk of developing breast and up to a 60% risk of ovarian cancer [2,3,4]. Understanding how modifiable and lifestyle risk factors affect cancer risk, in BRCA mutation carriers, may have important implications for cancer prevention in this high risk group
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