Functional IFNG polymorphism in intron 1 in association with an increased risk to promote sporadic breast cancer

Interferon (IFN)-gamma is an important Th1 cytokine, which plays a role in immune surveillance and anti-tumor activity. A case-control study involving 54 sporadic breast cancer patients and 144 healthy controls was carried out to explore if the genotype variation of a proposed non-specific enhancer element with a dinucleotide (CA)(n) repeat in intron 1 has a role in the susceptibility to promote sporadic breast cancer. Genotype analysis carried out by single-strand length polymorphism and confirmed by sequencing showed an increased frequency of (CA)(12) allele (P<0.001) and decreased frequencies of (CA)(15) (P<0.01) and (CA)(>15) (p<0.001) alleles in sporadic breast cancer patients as compared to controls. Further, in vitro reporter assays for (CA)(12) and (CA)(15) alleles suggested these to be associated with decreased and increased expressions, respectively, suggesting the (CA)(12)/(CA)(12) background to act as one of the factors that could lead to low production of IFN-gamma. The study concludes that such genetic background for a proposed nonspecific enhancer element with (CA)(n) repeat within intron 1 of the IFNG gene might put the individuals with this genotype at higher risk to promote the development of sporadic breast cancer due to a resultant compromised immune surveillance.