rs1045485

This systematic review analyzed 24 studies examining 31 genes and 62 genetic variants associated with anterior cruciate ligament rupture (ACLR). Key findings show mixed evidence for collagen variants: COL1A1 rs1800012 showed protective association in European ancestry populations (OR=2.8, p=0.040), while COL1A2 rs42524 and rs2621215 conferred increased risk (OR=5.73 and 4.29 respectively). VEGFA polymorphisms rs2010963 and rs699947 showed conflicting associations across studies, and most major variants in IL6, IL1B, MMP genes, and inflammatory markers showed no consistent associations with ACLR across populations, highlighting the need for gender and ancestry-stratified analyses.

PhD dissertation examining genetic variants in collagen genes (COL22A1, COL27A1, COL11A1) and anterior cruciate ligament injury risk in Polish athletes. Paper 1 is a systematic review of genetic determinants of ACL rupture. Papers 2 and 3 are case-control association studies finding no significant associations between SNPs rs11784270/rs6577958 (COL22A1), rs946053 (COL27A1), and rs3753841 (COL11A1) and non-contact ACL injury risk in Polish athletes.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

This case-control study evaluated rare copy number variants (CNVs), protein-truncating variants, and missense mutations in DNA damage response genes for breast cancer association in Finnish cohorts. CYP2C19 deletion showed enrichment in triple-negative breast cancer (p=0.021). TEX15 c.7253dupT frameshift variant associated with hereditary breast cancer (p=0.018). FANCD2 c.2715+1G>A splice-site variant (rs201811817) showed 7.5-fold increased risk (p=0.036, OR=7.5). RECQL p.Ile156Met and POLG p.Leu392Val (rs145289229) missense variants also associated with breast cancer (p=0.043 and p=0.010, OR=2.1 respectively).

This pooled analysis of 796 aggressive prostate cancer cases and 2,060 controls across three cohorts (Washington University, Johns Hopkins, and PLCO) demonstrates that the histidine allele of CASP8 D302H (rs1045485) is associated with a significantly reduced risk of aggressive prostate carcinoma (OR per allele = 0.67, 95% CI: 0.54-0.83, P=0.0003). The protective effect was specific to aggressive disease, with no association observed for indolent/localized, low-grade disease.

This meta-analysis of 13 studies (8 publications) with 13,058 cases and 14,418 controls examined the association between CASP8 rs3834129 (-652 6N insertion/deletion) polymorphism and colorectal cancer (CRC) susceptibility. The heterozygous ID vs II genotype showed a statistically significant protective effect (OR=0.94, 95% CI=0.88-0.99), with stronger protection observed in Asian populations (OR=0.86, 95% CI=0.76-0.98). However, no significant associations were found in homozygous and allele models, indicating a weak protective effect overall.

A systematic review and meta-analysis of 161 published meta-analyses evaluating 344 gene-variant/cancer associations across 99 genes and 18 cancer sites. The authors calculated false-positive report probability (FPRP) values to evaluate the robustness of statistically significant findings (p<0.05). The most noteworthy associations at very low prior probability were GSTM1 null with bladder cancer (OR: 1.5, p=1.9×10-14), NAT2 slow acetylator with bladder cancer (OR: 1.46, p=2.5×10-7), MTHFR C677T with gastric cancer (OR: 1.52, p=4.9×10-8), and GSTM1 null with acute leukemia (OR: 1.20, p=8.6×10-15). Phase II metabolizing enzymes, particularly GSTM1 deletion, showed the most consistent and highly significant associations with cancer risk.

A hospital-based case-control study of 805 cutaneous melanoma patients and 835 controls examined three functional polymorphisms in caspase-8 and caspase-10 genes. CASP8 D302H (rs1045485:G>C) and CASP8 -652 6N del (rs3834129:-/CTTACT) variant genotypes were associated with significantly lower melanoma risk (adjusted OR 0.70 and 0.74 respectively), while CASP10 I522L (rs13006529:A>T) showed no significant association. The D-del-I haplotype was associated with substantially reduced melanoma risk (OR 0.52).

This consortium analysis of 14 case-control studies (4,624 ovarian cancer cases and 8,113 controls) evaluated 7 candidate SNPs (AURKA rs2273535, BRCA2 rs144848, RB1 rs2854344, CDKN2A rs2811712, SRD5A2 rs523349/rs632148, CASP8 rs1045485, TGFB1 rs1982073) for association with ovarian cancer risk. Only RB1 rs2854344 showed a marginally significant association with decreased ovarian cancer risk (ordinal OR 0.88, 95% CI 0.79-1.00, p=0.041; dominant OR 0.87, 95% CI 0.76-0.98, p=0.025), while AURKA showed suggestive evidence when heterogeneous studies were excluded (ordinal OR 1.10, p=0.027). The other 5 SNPs showed no significant association, providing informative null results.