BC is by far the most common malignancy affecting Western women. A family history of BC is one of the most important and consistent risk factors, highlighting the role of inherited germline susceptibility genes. In the mid 1990s, two BC susceptibility genes, BRCA 1 (chromosome 17) and BRCA 2 (chromosome 13) were identified.119,120 Mutations that render these genes nonfunctional or absent are inherited in an autosomal dominant manner and confer a high disease risk. However, recent epidemiological studies suggest that BRCA 1 and BRCA 2 mutations only account for a few percent of BC cases.121 It is highly likely that a number of more prevalent, low penetrance genes contribute to BC susceptibility in a larger population of women and are therefore responsible for a greater proportion of the disease burden.121-123 Recent modelling of breast cancer inheritance in a population where BRCA1 and 2 gene carriers had been excluded from the cohort revealed a model of inheritance that is polygenic and provides an estimate that nearly 90% of all breast cancer cases will occur in an identifiable subset of perhaps half the general population.124 As yet, little is known about low penetrance susceptibility genes which contribute to BC susceptibility and only a few have been identified, including genes involved in carcinogen detoxification and oestrogen metabolism.125-127
There is accumulating evidence indicating the presence of peritumoral inflammatory infiltrate in BC, which may reflect—at least in part—an antitumor immune response, while angio-genesis is necessary for the development of BC and the extent of angiogenesis correlates with tumor development and patient survival.94-96 In addition, high levels of IL-10 mRNA are detectable in tumor lesions.128 Accordingly, we have performed a small study of 144 British Caucasian BC patients and 263 controls, for the same panel of SNPs in pro- and anti-inflammatory and pro-angiogenic cytokine genes as studied in PC, but have failed to demonstrate any associations with susceptibility to BC, for any of these SNPs, including IL-10 -1082—save for the TNFa -308 GG, which was increased in frequency in the BC group, at a marginal level of significance.77 Conversely, in an independent study of 125 Italian BC patients and 100 controls, Giordani et al78 have reported a significant association between the IL-10 -1082 AA 'low expression' genotype and BC, analogous to our findings in CMM and PC, but have failed to demonstrate any association between the TNFa -308 SNP and BC.
Therefore the limited data obtained to date with regard to IL-10 polymorphism and development of BC are equivocal, but suggest that a larger study of IL-10 -1082 and additional polymorphisms is merited in this very common cancer.
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