TY - JOUR
T1 - Validation of genetic sequence variants as prognostic factors in early-stage head and neck squamous cell cancer survival
AU - Azad, Abul Kalam
AU - Bairati, Isabelle
AU - Samson, Elodie
AU - Cheng, Dangxiao
AU - Mirshams, Maryam
AU - Qiu, Xin
AU - Savas, Sevtap
AU - Waldron, John
AU - Wang, Changshu
AU - Goldstein, David
AU - Xu, Wei
AU - Meyer, Francois
AU - Liu, Geoffrey
PY - 2012/1/1
Y1 - 2012/1/1
N2 - Purpose: From the published literature, we identified 23 germ line sequence variants in 17 genes from hypothesis-generating studies thatwere associated with prognosis of headandneck cancer, including sequence variants of DNA repair (ERCC1, ERCC4, ERCC5, MSH2, XPA, ERCC2, XRCC1, XRCC3), DNA methylation (DNMT3B), cell cycle and proliferation (CCND1, TP53), xenobiotic metabolism (GSTM1, GSTT1, CYP2D6), metastatic -potential (MMP3), immunologic (CTLA4), and growth factor pathways (FGFR4). The purpose of this study was to validate the role of these 23 sequence variants for overall (OS) and disease-free survival (DFS) in a large, comprehensive, well-annotated data set of patients with head and neck cancer. Experimental Design: We genotyped these sequence variants in 531 patients with stage I and II radiation-treated head and neck cancer (originally recruited for an alpha-tocopherol/beta-carotene placebo-controlled secondary prevention study), and analyzed using Cox proportional hazards models, stratified by treatment arm, adjusting for clinical prognostic factors. Results: Two OS associations were statistically significant for each variant allele when compared with the wild-type: CTLA4:A49G [rs231775; adjusted HR (aHR), 1.32 (1.1-1.6); P = 0.01] and XRCC1:Arg339Gln [rs25487; aHR, 1.28 (1.05-1.57); P = 0.02]. Both of these sequence variants had significant results in the opposite direction as prior published literature. Two DFS associations were of borderline significance in the same direction as prior literature: ERCC2:Lys751Gln [rs13181; aHR, 0.80 (0.6-1.0); P = 0.05] and TP53: Arg72Pro [rs1042522; aHR, 1.28 (1.0-1.6); P = 0.03], comparing number of variant alleles with reference of zero variants. Conclusions: None of the prognostic sequence variants previously published was validated for OS in our patients with early-stage radiation-treated head and neck cancer, though rs1381and rs1042522 had borderline significant association with DFS.
AB - Purpose: From the published literature, we identified 23 germ line sequence variants in 17 genes from hypothesis-generating studies thatwere associated with prognosis of headandneck cancer, including sequence variants of DNA repair (ERCC1, ERCC4, ERCC5, MSH2, XPA, ERCC2, XRCC1, XRCC3), DNA methylation (DNMT3B), cell cycle and proliferation (CCND1, TP53), xenobiotic metabolism (GSTM1, GSTT1, CYP2D6), metastatic -potential (MMP3), immunologic (CTLA4), and growth factor pathways (FGFR4). The purpose of this study was to validate the role of these 23 sequence variants for overall (OS) and disease-free survival (DFS) in a large, comprehensive, well-annotated data set of patients with head and neck cancer. Experimental Design: We genotyped these sequence variants in 531 patients with stage I and II radiation-treated head and neck cancer (originally recruited for an alpha-tocopherol/beta-carotene placebo-controlled secondary prevention study), and analyzed using Cox proportional hazards models, stratified by treatment arm, adjusting for clinical prognostic factors. Results: Two OS associations were statistically significant for each variant allele when compared with the wild-type: CTLA4:A49G [rs231775; adjusted HR (aHR), 1.32 (1.1-1.6); P = 0.01] and XRCC1:Arg339Gln [rs25487; aHR, 1.28 (1.05-1.57); P = 0.02]. Both of these sequence variants had significant results in the opposite direction as prior published literature. Two DFS associations were of borderline significance in the same direction as prior literature: ERCC2:Lys751Gln [rs13181; aHR, 0.80 (0.6-1.0); P = 0.05] and TP53: Arg72Pro [rs1042522; aHR, 1.28 (1.0-1.6); P = 0.03], comparing number of variant alleles with reference of zero variants. Conclusions: None of the prognostic sequence variants previously published was validated for OS in our patients with early-stage radiation-treated head and neck cancer, though rs1381and rs1042522 had borderline significant association with DFS.
UR - http://www.scopus.com/inward/record.url?scp=84855438473&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855438473&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-11-1759
DO - 10.1158/1078-0432.CCR-11-1759
M3 - Article
C2 - 22076708
AN - SCOPUS:84855438473
SN - 1078-0432
VL - 18
SP - 196
EP - 206
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -
