1.
Fc-γ Receptor Polymorphisms, Cetuximab Therapy, and Survival in the NCIC CTG CO.17 Trial of Colorectal Cancer.
Liu, G, Tu, D, Lewis, M, Cheng, D, Sullivan, LA, Chen, Z, Morgen, E, Simes, J, Price, TJ, Tebbutt, NC, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2016;(10):2435-44
Abstract
PURPOSE Two germline Fc-γ receptor (FCGR) polymorphisms, rs1801274 [FCGR2A;His(H)131Arg(R)] and rs396991 [FCGR3A;Phe(F)158Val(V)] produce altered proteins through amino acid substitutions; both are reported to be associated with cetuximab-related outcomes. We performed a validation of these polymorphisms in NCIC CTG CO.17, a randomized trial of cetuximab monotherapy in refractory, metastatic colorectal cancer expressing EGFR. EXPERIMENTAL DESIGN DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped. In addition to log-rank tests, Cox proportional hazard models assessed their relationships with overall (OS) and progression-free survival (PFS), adjusting for clinically important prognostic factors, along with a polymorphism-treatment arm interaction term. RESULTS Somatic KRAS status was wild-type for exon 2 in 153 (52%) of 293 patients, from whom tumor DNA was available. For FCGR2A H/H, a genotype-treatment interaction for KRAS wild-type patients was observed for OS (P = 0.03). In KRAS wild-type patients carrying FCGR2A H/H, cetuximab (vs. no cetuximab) improved survival substantially, with adjusted HRs (aHR) of 0.36 (OS) and 0.19 (PFS) and absolute benefits of 5.5 months (OS; P = 0.003) and 3.7 months (PFS; P = 0.02). In contrast, patients carrying FCGR2A R alleles (H/R or R/R) had aHRs of only 0.78 (OS; 2.8-month benefit) and 0.53 (PFS; 1.6-month benefit). No relationships were found for rs396991 (FCGR3A). CONCLUSIONS In the CO.17 trial, cetuximab worked best for patients with KRAS wild-type colorectal cancers carrying FCGR2A H/H genotypes. Significantly lower benefits were observed in patients carrying germline FCGR2A R alleles. Clin Cancer Res; 22(10); 2435-44. ©2016 AACR.
2.
Vitamin D receptor BsmІ polymorphism and ovarian cancer risk: a meta-analysis.
Qin, X, Lu, Y, Qin, A, Chen, Z, Peng, Q, Deng, Y, Xie, L, Wang, J, Li, R, Zeng, J, et al
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2013;(7):1178-83
Abstract
OBJECTIVE Vitamin D receptor (VDR) FokI polymorphism has been reported to influence ovarian cancer (OC) susceptibility, but the association between VDR BsmI polymorphism and OC risk remains controversial. To clarify the relationship between them, we performed a meta-analysis. METHODS A comprehensive literature search was conducted to examine all the eligible studies of VDR BsmI polymorphism and OC risk. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to assess the strength of this association. RESULTS Seven separate comparisons consisting of 1977 OC cases and 2832 healthy controls were included in our meta-analysis. The pooled analyses showed no significant association between VDR BsmI G/A polymorphism and OC in all of the comparisons (AA vs GG: OR, 1.01; P = 0.919; AG vs GG: OR, 1.12; P = 0.087; AG + AA vs GG: OR, 1.10; P = 0.146; AA vs AG + GG: OR, 0.96; P = 0.629). However, subgroup analysis showed a significant contribution of the dominant inheritance model to OC development in the European group: AG + AA vs GG (OR, 1.43; P = 0.029); AG vs GG (OR, 1.46; P = 0.031). CONCLUSIONS Vitamin D receptor BsmI G/A gene variant might be a moderate risk factor of OC development in the European population instead of North America or Asian population.