rs1800797

This case-control study analyzes 28 SNPs in 26 inflammatory response genes in 343 patients (100 with appendicitis, 243 controls) using TaqMan genotyping. Significant associations were found for IL-13 rs1800925 (OR=6.02, 95% CI 1.52-23.78), IL-17 rs2275913 (OR=2.38, 95% CI 1.24-4.57), and CCL22 rs223888 (OR=0.12, 95% CI 0.02-0.90), suggesting a genetic-driven inflammatory response as a pathogenic mechanism in appendicitis.

This case-control study of 1,088 Chinese Han women (360 cases, 728 controls) found that IL-6 gene polymorphisms rs1800795 and rs2069837 were significantly associated with cervical cancer risk, with adjusted OR 1.60 (95% CI 1.24-2.19) and 1.49 (95% CI 1.19-2.07) respectively. GMDR analysis revealed significant gene-gene interaction between these two SNPs (p=0.0010), with combined genotypes (GC/CC + AG/GG) conferring highest risk: OR 3.35 (95% CI 2.01-4.78).

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 PhD thesis investigated pharmacogenetics of microRNAs and immune system genes in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy. In 265 LARC patients, five SNPs were identified as predictive biomarkers of pathological response: DROSHA-rs10719 (OR=1.87, p=0.0274) and SMAD3-rs17228212 (OR=2.01, p=0.0049) were unfavorable, while SMAD3-rs744910 (OR=0.45, p=0.0153), SMAD3-rs745103 (OR=0.48, p=0.0471), and TRBP-rs6088619 (OR=0.39, p=0.0125) were protective. In 235 LARC patients, three prognostic biomarkers for 2-year disease-free survival were identified: IL17F-rs641701 (HR=3.23, p=0.003), IL17F-rs9463772 (HR=2.89, p=0.002), and STAT3-rs8069645 (HR=0.50, p=0.044).

This candidate gene association study of 370 CCA cases and 740 controls identified initial associations between COX-2 variants rs2143417 (OR=1.52) and rs689466 (OR=1.36) and cholangiocarcinoma risk; however, these findings failed replication in an independent cohort of 212 cases and 424 controls (rs2143417 OR=1.04, rs689466 OR=1.08). No SNP variants showed significant associations with CCA survival, and NKG2D variants previously reported to be associated with CCA did not replicate.

Two-stage case-control study (1,584 cervical cancer cases, 1,768 controls) in Eastern Chinese women found IL6 rs2069837 SNP associated with increased cervical cancer risk (OR 1.27, 95% CI 1.08-1.49, dominant model, p=0.004; OR 1.19, 95% CI 1.04-1.36, additive model, p=0.014). IL6 rs2069837 AG/GG carriers showed significantly higher IL6 protein expression levels than AA carriers. Evidence of gene-environment interaction with age at primiparity and menopausal status in cervical cancer development.

Turkish case-control study examining TRAIL and TRAIL-DR4 gene polymorphisms in gastric cancer. Compared TRAIL C1595T (rs1131580) and TRAIL-DR4 C626G (rs20575) genotype frequencies between 50 gastric cancer patients and 163 healthy controls. No significant association found between either polymorphism and gastric cancer risk (p>0.256, p>0.189) or clinical parameters including tumor stage, lymph node involvement, distant metastasis, and perineural invasion. Serum TRAIL levels were also not significantly different between groups (p>0.33).

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.

This PhD thesis comprises four association studies examining inherited variations in inflammatory cytokine genes and their pathogenetic role in rheumatoid arthritis (RA), multiple myeloma (MM), and B-cell non-Hodgkin's lymphoma (B-NHL). Paper I found that CHI3L1 promoter polymorphisms (rs4950928) were significantly associated with serum YKL-40 concentrations in 238 RA patients (P < 2.0e-16) and 605 controls. Paper IV reported CHI3L1 rs4950928 associated with follicular lymphoma 10-year overall survival (HRCG = 2.04, 95% CI 1.17-3.54). Papers II and III examined gene-gene interactions in MM and B-NHL risk and prognosis.

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.