rs3024496

This case-control study within the IMMEnSE consortium (3,056 MM patients and 1,960 controls) investigated associations between polymorphic 3' untranslated region (p3UTR) variants in six candidate genes and multiple myeloma (MM) risk and overall survival. IL10 rs3024496 A-allele showed significant association with increased MM risk (OR=1.20-1.24) and shorter overall survival (HR=1.42-1.44). Functional studies demonstrated the A-allele decreased IL10 mRNA expression by ~6%, consistent with in vivo GTEx data, suggesting rs3024496 modulates immune homeostasis and disease prognosis in MM.

A case-control study of 540 cases and 400 controls in Bangladesh examined 25 candidate SNPs in inflammation, one-carbon metabolism, and skin cancer genes for associations with arsenic-induced skin lesions. Six SNPs showed significant gene-environment interactions with water arsenic exposure (PEMT rs2278952 P=0.004, rs897453 P=0.05; DHFR rs1650697 P=0.02; IL10 rs3024496 P=0.04; INPP5A rs1133400 P=0.03; XPC rs2228000 P=0.01), and the INPP5A rs1133400 interaction was successfully replicated in an independent population of 488 cases and 2,794 controls (P=0.03).

This prospective case-control study examined genetic variation in immune response genes and prostate cancer risk in the Prostate Cancer Prevention Trial (PCPT) placebo arm. Among 881 cases and 848 controls, the minor allele of rs3212227 in IL12(p40) was associated with increased prostate cancer risk (OR=1.30, 95% CI 1.10-1.53, P-trend=0.0017), particularly for lower-grade disease. The minor alleles of IL10 tagSNPs rs3021094 (OR=1.31, 95% CI 1.03-1.66, P-trend=0.03) and rs1800890 (OR=0.87, 95% CI 0.75-0.99, P-trend=0.04) showed significant associations. The study investigated whether observed associations were explained by PSA-associated detection bias and found that associations persisted in men with low PSA levels.

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.

Population-based case-control study of Connecticut women showing that genetic polymorphisms in IL10RA (rs9610) and TNF (rs1800629) genes modify the association between blood transfusion and non-Hodgkin lymphoma (NHL) risk. IL10RA rs9610 GG genotype carriers with transfusion history had increased NHL risk (OR=1.9, 95% CI: 1.1-3.2), while AG/AA carriers had decreased risk (OR=0.6, 95% CI: 0.4-0.9), with significant gene-transfusion interaction (P=0.003).

Nested case-control study of 258 prostate cancer cases and 258 matched controls in the CLUE II prospective cohort examining genetic variants in inflammation and obesity-related genes. The IL10 -1082G>A variant (rs1800896, A allele) was positively associated with prostate cancer risk (AG vs GG: OR=1.69, 95% CI 1.10-2.60; AA vs GG: OR=1.81, 95% CI 1.11-2.96), while a TLR4 variant (rs4986790) showed inverse association, and no consistent associations were found for obesity-related gene variants.

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.