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Opposing effects of pro‐ and anti‐inflammatory cytokine gene polymorphisms on the risk for breast cancer in western I ndian women: a pilot study
Author(s) -
Joshi N. N.,
Bhat S.,
Hake S.,
Kale M.,
Kannan S.
Publication year - 2014
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/iji.12098
Subject(s) - breast cancer , single nucleotide polymorphism , genotype , allele , snp , context (archaeology) , medicine , immunology , genotyping , cytokine , cancer , oncology , biology , gene , genetics , paleontology
In an earlier study, the genotypes associated with higher level of transforming growth factor‐β1 ( TGF ‐β1) were found to reduce the risk for breast cancer in western Indian women. This observation implied that gene polymorphisms affecting the levels of pro‐ and anti‐inflammatory cytokines may influence the risk for breast cancer in this population. Hence, we performed genotyping for three more functional single‐nucleotide polymorphisms ( SNP s) responsible for variations in the levels of cytokines associated with inflammation. To that effect, polymorphisms in genes coding for IL ‐4 ( IL ‐4 C‐590T; rs2243250), IFN ‐γ ( IFN ‐G A + 874T; rs2430561) and MCP ‐1 ( MCP ‐1 A‐2578G; rs1024611) were examined in premenopausal, healthy women ( N = 239) and patients with breast cancer ( N = 182) from western I ndia. In carriers of the IL ‐4*590T allele, a reduced risk for the disease (dominant model; OR = 0.61, 95% CI 0.37–0.98) was seen similar to that seen in TGF ‐B1 * 10C carriers. An opposite trend was observed with respect to the alleles associated with higher expression of MCP ‐1 or IFN ‐γ. In individuals positive for three or more alleles associated with higher levels of either pro‐ or anti‐inflammatory cytokines, an additive effect on the modulation of risk for the disease was evident (for TGF ‐B1 & IL ‐4 , OR = 0.33, 95% CI 0.12–0.87; for IFN ‐G & MCP ‐1 , OR = 2.29, 95% CI 0.95–5.51). In the context of contrasting observations in other populations, these results indicate a significant contribution of anti‐inflammatory genotypes in the modulation of risk for breast cancer in western Indian women.