title: Opposing effects of pro- and anti-inflammatory cytokine gene polymorphisms on the risk for breast cancer in western Indian women: a pilot study.
abstract: 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 (SNPs) 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 India. 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.
authors.affiliation: Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.
authors.forename: N N
authors.initials: NN
authors.lastname: Joshi
authors.forename: S
authors.initials: S
authors.lastname: Bhat
authors.forename: S
authors.initials: S
authors.lastname: Hake
authors.forename: M
authors.initials: M
authors.lastname: Kale
authors.forename: S
authors.initials: S
authors.lastname: Kannan
mesh_terms: D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics* / Q000276:immunology; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007194:India; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508598:IL4 protein, human; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D007371:Interferon-gamma