Associations of lung and upper aero-digestive tract (UADT) cancers with environmental factors, genetic polymorphisms, and tumor biomarkers in a population-based case-control study

We used logistic regression in a Los Angeles County-based case-control study (611 lung and 601 upper aero-digestive tract [UADT] cancers 1040 controls) to evaluate associations of (1) lung and UADT cancers with environmental factors (2) inflammatory SNPs with lung and UADT cancers and (3) tumor biomarker expression in lung tumor samples. Lung tumor specimens were assayed for human papillomavirus (HPV) DNA by PCR (n=190) and for p16, p53, DNMT1, and FHIT protein expression by immunohistochemistry (n=189).Tobacco smoking was associated with lung cancer among ever smokers after adjusting for age, ethnicity, gender, education, and alcohol drinking (adjusted odds ratio [aOR] = 3.81, 95% confidence interval [CI]: 2.91--4.99). Consumption of more than two alcoholic drinks per day was associated with UADT cancer (aOR = 2.69, 95% CI: 2.03--3.58). Compared to subjects with neither self-reported physician-diagnosed asthma nor hay fever, individuals reporting both conditions were less likely to be lung (aOR = 0.45, 95% CI: 0.23--0.88) or UADT (aOR = 0.38, 95% CI: 0.18--0.78) cancer cases, or among all cancer sites combined (aOR = 0.48, 95% CI: 0.29--0.78). HPV DNA was not detected in he lung tumor specimens following PGMY/GP+ nested PCR.IL10 rs1800871 was associated with lung cancer among never smokers (aOR: 2.50, 95% CI: 1.25--5.00) and with UADT cancer (aOR = 0.40, 95% CI: 0.22--0.72) among heavy drinkers. In our pooled analysis of 1,212 cases and 1,040 controls, the IL1B rs16944 was associated with lung and UADT cancers (aOR = 1.32, 95% CI: 1.06--1.64). Less than multiplicative interaction was suggested for recessive IL10 rs1800871 and tobacco smoking for lung cancer. Adverse expression of 3 or 4 tumor proteins was associated with ever smoking (aOR = 3.54, 95% CI: 1.06--11.83) and with IL10 rs1800871 (aOR = 0.27, 95% CI: 0.11--0.65). We demonstrated inverse associations between respiratory allergies and cancer. We did not find an association between HPV and lung cancer, which may be explained by sample size and specimen quality. IL10 rs1800871 may be a susceptibility marker for lung and oropharyngeal cancers. Bayesian correction for multiple comparisons suggests that chance is an unlikely explanation.