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

Interferon (IFN)- 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-. The study concludes that such genetic background for a proposed non-specific 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.Anjana Saha and Ashish Dhir contributed equally.