rs746868

Case-control study of 1,514 women (Stage I) replicated in 2,672 women (Stage II) examining 47 SNPs in 26 cytokine and cytokine receptor genes of the adaptive immune response pathway associated with breast cancer risk. The study identified differential associations by ancestry, with five SNPs showing highly significant combined effect in African American women (P-trend=0.0005), where individuals with 3+ protective genotypes had approximately 50% reduced breast cancer risk. Key associated SNPs included rs1041981, rs1800469, rs2243250, and others in immune response genes including IL4, IL4R, IL10RA, TGFB1, and IL13.

A case-control study of 127 multiple myeloma (MM) cases and 545 controls examined 82 common variants in 45 genes mediating immunity. IL4R rs2107356 (−28120T homozygotes, OR=1.91, 95% CI 1.08-3.38) and FCGR2A rs1801274 (−120G homozygotes, OR=1.95, 95% CI 1.06-3.60) were significantly associated with increased MM risk. A haplotype in the LTA*TNF complex (LTA −82C/−90G*TNF −1036C/−487G/−417G, OR=1.63, 95% CI 1.02-2.61) was also associated with increased MM risk compared to controls.

A large population-based case-control study of TNF-LTA genetic variation in 5,546 breast cancer cases and 5,219 controls (USA and Poland cohorts) found that the variant A allele of rs361525 in the TNF promoter region was associated with modestly increased breast cancer risk (per allele OR=1.18, 95% CI 1.04-1.35, p=0.008). Eight TNF and LTA SNPs were genotyped; haplotype analyses showed the GAG haplotype carrying rs361525 A was associated with elevated risk, while the well-studied TNF-308 variant (rs1800629) showed no association.