Abstract 4656: Relationship of nicotine and carcinogen biomarkers to lung cancer risk among smokers in the Shanghai cohort study

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 8_Supplement; p. 4656
• Main Authors: Murphy, Sharon E., Berg, Jeannette Zinggeler, Wang, Renwei, Wickham, Katherine M., Gao, Yu-Tang, Hecht, Stephen S., Yuan, Jian-Min
• Format: Journal Article
• Language: English
• Published: 15.04.2011
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-4656

Abstract Individuals who develop lung cancer are predominantly tobacco users and further risk profiling within this group is important to better understand cancer susceptibility and could be used to target interventions. A nested case-control approach was used to evaluate risk factors for lung cancer in a population of Chinese men from Shanghai, China (317 cases and 317 controls). All participants were current smokers at baseline and controls were matched for age, neighborhood, and date of biospecimen collection. Biomarkers assessed in urine were nicotine and its major metabolites, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a tobacco carcinogen), and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT, a biomarker of polyaromatic hydrocarbons). The odds ratio for developing lung cancer were greatest for men with the highest versus lowest quintile of urinary cotinine (cotinine + cotinine glucuronide), OR (95% CI); 8.79 (4.42-17.47) unadjusted, and 5.26 (2.39-11.57) adjusted for years of smoking, cigarettes per day, NNAL, and PheT. Cotinine levels are influenced both by nicotine exposure and metabolism. Nicotine and cotinine are metabolized by cytochrome P450 2A6 which is polymorphic and ∼15% of the Chinese population carry low activity alleles. In contrast, nicotine equivalents is a biomarker of exposure that is less influenced by metabolism as it is the sum of nicotine and its metabolites excreted in urine. Higher odds ratios of lung cancer were also observed for increasing nicotine equivalents but this was a weaker biomarker compared to cotinine in this population, OR (95% CI); 4.86 (2.72-8.69) unadjusted, and 2.58 (1.32-5.03) adjusted for years of smoking, cigarettes per day, NNAL, and PheT. The ratio of trans-3′-hydroxycotinine to cotinine per nicotine equivalents was evaluated as a biomarker of oxidation phenotype. Previously the ratio of trans-3′-hydroxycotinine to cotinine has been used to phenotype individuals for P450 2A6 activity, and to account for variation in nicotine dose during smoking the ratio was expressed per nicotine equivalents. Unexpectedly, the highest quintile of the metabolite ratio was associated with a decreased risk of lung cancer compared to the lowest quintile, OR (95%CI); 0.26 (0.15-0.47). This group would include individuals who have a low nicotine metabolism phenotype and smoke an average-to-high amount. Higher urinary NNAL and PheT were also risk factors for lung cancer albeit the odds ratios were lower than for cotinine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4656. doi:10.1158/1538-7445.AM2011-4656