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

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 5 0.89) but it did for the HPV16 seronegative (p interaction 50.04). 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. ' 2009 Wiley-Liss, Inc.Key words: Human papillomavirus (HPV); head and neck squamous cell carcinoma (HNSCC); tobacco; XRCC1; DNA repair Approximately 434,000 new cases of head and neck squamous cell carcinoma (HNSCC) are expected worldwide annually 1 and over 45,000 of these will occur in the U.S.2 Tobacco and alcohol together are thought to explain 75% of HNSCC incidence.3 The predominant risk factor, tobacco, contains numerous known carcinogens including benzene, polycyclic aromatic hydrocarbons and nitrosamines. A review of the literature found that smokers are at a 3-to 12-fold greater risk of HNSCC than nonsmokers and among those who do not drink alcohol, the relative risks for smoking were between 2 and 5.

Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma

“…To our knowledge, there are no previous studies on the function of c.-77T>C SNP on OPSCC or overall HNSCC risk. We also found no association of XRCC1 c.839G>A and c.1196G>A SNPs with OPSCC risk, according to previous results from overall HNSCC studies (Sturgis et al 1999;Tae et al 2004;Demokan et al 2005;Matullo et al 2006;Li et al 2007;Harth et al 2008;Applebaum et al 2009;Csejtei et al 2009;Kowalski et al 2009;Gugatschka et al 2011;Al-Hadyan et al 2012;Yuan et al 2012). In contrast, the variant allele A of c.1196G>A SNP was associated with decreased risk (Olshan et al 2002;Kumar et al 2012;Khlifi et al 2014) and increased risk (Choudhury et al 2014) of overall HNSCC.…”

“…The roles of the OGG1 c.977C>G (Elahi et al 2002;Zhang et al 2004;Matullo et al 2006;Görgens et al 2007;Hall et al 2007;Kumar et al 2011;Mitra et al 2011), APEX1 c.444T>G (Matullo et al 2006;Li et al 2007); XRCC1 c.-77T>C, c.580C>T (Sturgis et al 1999;Olshan et al 2002;Tae et al 2004;Demokan et al 2005;Matullo et al 2006;Applebaum et al 2009;Csejtei et al 2009;Kowalski et al 2009;Gugatschka et al 2011;Kumar et al 2012), c.839G>A (Tae et al 2004;Applebaum et al 2009;Gugatschka et al 2011;Kumar et al 2012) and c.1196G>A (Sturgis et al 1999;Olshan et al 2002;Tae et al 2004;Demokan et al 2005;Matullo et al 2006;Li et al 2007;Harth et al 2008;Applebaum et al 2009;Csejtei et al 2009;Kowalski et al 2009;Gugatschka et al 2011;AlHadyan et al 2012;Kumar et al 2012;Yuan et al 2012;Choudhury et al 2014;Khlifi et al 2014) SNPs in overall HNSCC risk are still controversial or unknown.…”

Peripheral blood DNA methylation profiles are indicative of head and neck squamous cell carcinoma: An epigenome-wide association study

“…The study population consisted of 92 HNSCC cases and 92 cancer-free control subjects with available peripheral blood samples, randomly selected from a previously described case-control study of head and neck cancer. 43 Briefly, the case-control study was comprised of incident head and neck cancer patients from the greater Boston area, and populationbased controls from the same region with no prior history of cancer, frequency-matched on age and gender. Subjects completed a self-administered questionnaire that provided data on sociodemographics, personal characteristics, personal and family cancer history, and exposures.…”

Leukocyte-adjusted epigenome-wide association studies of blood from solid tumor patients

“…EWAS were performed on three separate previously described population-based case-control studies of bladder cancer (223 cases, 205 controls), 39,40 head and neck squamous cell carcinoma (HNSCC; 92 cases, 92 controls), 35,41 and a publicly available data set for ovarian cancer (131 cases and 274 controls). 32 A description of each of the three study populations is provided in Table 1.…”

“…The second study consisted of 92 incident head and neck squamous cell carcinoma (HNSCC) cases and 92 cancer-free control subjects with available blood samples (GEO: GSE30229), randomly selected from a previously described case-control study of head and neck cancer. 35,41 Briefly, the study was comprised of incident head and neck cancer patients from the greater Boston area and populationbased controls from the same region with no prior history of cancer, frequency-matched on age (+/-3 y), gender, and town of residence. Subjects completed a self-administered questionnaire that provided data on sociodemographic, health behavior and exposure history.…”