rs375947

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.

This is a comprehensive mutation update and database description paper for the IL12RB1 gene, which encodes the IL-12 receptor β1 chain. The authors review 70 unique pathogenic mutations found in 198 individuals worldwide causing IL-12R β1 deficiency, an autosomal recessive disorder characterized by increased susceptibility to mycobacterial and salmonella infections. The paper also reports 115 variations of unknown significance and reviews associations of IL12RB1 polymorphisms (rs11575925, rs147215816, rs11575926, rs11575934, rs375947, rs401502, rs11575935) with tuberculosis and other diseases, though most reported associations have not been replicated in larger cohorts.

This hybrid case-parent triad and case-control study examined associations between 76 tagSNPs in IL10 and IL12 cytokine pathway genes (IL10, IL12A, IL12B, IL10RA, IL10RB, IL12RB1, IL12RB2) and cervical/vulvar cancer risk. Key findings include: IL10RA rs9610 (OR=1.76, 95% CI 1.15–2.68) and rs4252314 (OR=2.23, 95% CI 1.26–3.96) associated with increased cervical cancer risk; IL12RB2 rs4297265 (OR=0.46) and rs2229546 (OR=0.43) associated with reduced cervical SCC risk; IL12B rs3181224 associated with reduced vulvar SCC risk (OR=0.30, 95% CI 0.12–0.74); and IL12RB1 rs11575934 (OR=1.51, 95% CI 1.12–2.05) associated with increased cervical adenocarcinoma risk.

This case-control study of 763 Crohn's disease cases and 254 healthy controls investigated 10 genes in the IL23/IL17 pathway, identifying novel haplotype associations in IL17A (p=0.02), IL17RA (p=0.001), IL17RD (p=0.001), IL12RB1 (p=0.003), and IL12RB2 (p=0.001). Combined risk haplotypes from multiple pathway genes showed cumulative effect with OR=4.3 for 5 risk haplotypes (p=1.7×10⁻⁷), and significant epistatic interactions were observed between IL17A and IL23R variants (p=0.047) and between IL17RA and IL23R variants (p=0.036).