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Smoking modifies the relationship between XRCC1 haplotypes and HPV16-negative head and neck squamous cell carcinoma.

Authors
Applebaum-KM; McClean-MD; Nelson-HH; Marsit-CJ; Christensen-BC; Kelsey-KT
Source
Int J Cancer 2009 Jun; 124(11):2690-2696
NIOSHTIC No.
20035276
Abstract
Reports on the relationship between head and neck squamous cell carcinoma (HNSCC) and polymorphisms in X-ray cross complementing group 1 (XRCC1) have been inconsistent. We hypothesized this may be due to not accounting for Human papillomavirus type-16 (HPV16) and thus examined whether smoking modified the association between XRCC1 haplotypes and HNSCC risk within HPV16 serologic strata. Cases were diagnosed in Greater Boston, Massachusetts. Controls were matched to cases on age, gender and residential town. Genotyping was conducted on three XRCC1 polymorphisms (Arg194Trp, Arg280His and Arg399Gln) and serology was used to determine HPV16 exposure. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, sex, race, education, smoking, alcohol consumption and HPV16 serology. There was no overall association between XRCC1 polymorphisms and HNSCC risk. Smoking did not modify the association between XRCC1 polymorphisms and HNSCC risk among the HPV16 seropositive (p(interaction) = 0.89) but it did for the HPV16 seronegative (p(interaction)=0.04). Among the HPV16 seronegative, heavy smokers with a haplotype containing a variant allele had an increased HNSCC risk (haplotype with 399Gln: OR, 1.35; 95% CI, 0.97-1.86), whereas never/light smokers with variant alleles may have a reduced risk. In sum, the association between XRCC1 and HNSCC risk differed by HPV16 status and smoking. Among the HPV16 seronegative, heavy smokers with XRCC1 variant alleles had an increased HNSCC risk. There was no relationship between XRCC1 and HPV16-related HNSCC, regardless of smoking. Our findings underscore the importance of accounting for HPV16 exposure even when studying susceptibility to HNSCC.
Keywords
Age-factors; Disease-incidence; Disease-vectors; Exposure-methods; Genes; Genetic-factors; Genetics; Tobacco; Author Keywords: Human papillomavirus (HPV); head and neck squamous cell carcinoma (HNSCC); tobacco; XRCC1; DNA repair
Contact
Karl T. Kelsey, Center for Environmental Health and Technology, Departments of Community Health and Pathology and Laboratory Medicine, Brown University, Providence, RI 02912
CODEN
IJCNAW
Publication Date
20090601
Document Type
Journal Article
Email Address
karl_kelsey@brown.edu
Funding Type
Grant
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-K01-OH-009390
Issue of Publication
11
ISSN
0020-7136
Priority Area
Manufacturing
Source Name
International Journal of Cancer
State
MA; RI
Performing Organization
Boston University Medical Campus
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