Single nucleotide polymorphisms in nucleotide excision repair genes, cancer treatment, and head and neck cancer survival.
OBJECTIVE
Head and neck cancers (HNC) are commonly treated with radiation and platinum-based chemotherapy, which produce bulky DNA adducts to eradicate cancerous cells. Because nucleotide excision repair (NER) enzymes remove adducts, variants in NER genes may be associated with survival among HNC cases both independently and jointly with treatment.


METHODS
Cox proportional hazards models were used to estimate race-stratified (White, African American) hazard ratios (HRs) and 95 % confidence intervals for overall (OS) and disease-specific (DS) survival based on treatment (combinations of surgery, radiation, and chemotherapy) and 84 single nucleotide polymorphisms (SNPs) in 15 NER genes among 1,227 HNC cases from the Carolina Head and Neck Cancer Epidemiology Study.


RESULTS
None of the NER variants evaluated were associated with survival at a Bonferroni-corrected alpha of 0.0006. However, rs3136038 [OS HR = 0.79 (0.65, 0.97), DS HR = 0.69 (0.51, 0.93)] and rs3136130 [OS HR = 0.78 (0.64, 0.96), DS HR = 0.68 (0.50, 0.92)] of ERCC4 and rs50871 [OS HR = 0.80 (0.64, 1.00), DS HR = 0.67 (0.48, 0.92)] of ERCC2 among Whites, and rs2607755 [OS HR = 0.62 (0.45, 0.86), DS HR = 0.51 (0.30, 0.86)] of XPC among African Americans were suggestively associated with survival at an uncorrected alpha of 0.05. Three SNP-treatment joint effects showed possible departures from additivity among Whites.


CONCLUSIONS
Our study, a large and extensive evaluation of SNPs in NER genes and HNC survival, identified mostly null associations, though a few variants were suggestively associated with survival and potentially interacted additively with treatment.
Department of Epidemiology, Gillings School of Global Pubic Health, University of North Carolina at Chapel Hill, 2101B McGavran-Greenberg Hall, CB 7435, Chapel Hill, NC, 27599, USA, alayman@email.unc.edu.
Annah B
AB
Wyss
Mark C
MC
Weissler
Christy L
CL
Avery
Amy H
AH
Herring
Jeannette T
JT
Bensen
Jill S
JS
Barnholtz-Sloan
William K
WK
Funkhouser
Andrew F
AF
Olshan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics / Q000706:statistics & numerical data; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009657:North Carolina / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data; D055815:Young Adult; D001741:Black or African American