Yoder, Andrea R.

Exposure to polycyclic aromatic hydrocarbons (PAHs), byproducts of incomplete combustion, and their effects on the development of cancer are still being evaluated. Recent studies have analyzed the relationship between PAHs and tobacco or dietary intake in the form of processed foods and smoked/well-done meats. This study aims to assess the association of a blood biomarker and metabolite of PAHs, r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), dietary intake, selected metabolism SNPs, and pancreatic cancer. Demographics, food-frequency data, SNPs, treatment history, and levels of PheT in plasma were determined from 400 participants (202 cases and 198 controls) and evaluated based on pancreatic adenocarcinoma diagnosis. Demographic and dietary variables were selected based on previously published literature indicating association with pancreatic cancer. A multiple regression model combined the significant demographic and food items with SNPs. Final multivariate logistic regression significant factors (p-value < 0.05) associated with pancreatic cancer included: Type 2 Diabetes [OR = 6.26 (95% CI = 2.83, 14.46)], PheT [1.03 (1.02, 1.05)], very well-done red meat [0.90 (0.83, 0.96)], fruit/vegetable servings [1.35 (1.06, 1.73)], recessive (rs12203582) [4.11 (1.77, 9.91)], recessive (rs56679) [0.2 (0.06, 0.85)], overdominant (rs3784605) [3.14 (1.69, 6.01)], and overdominant (rs721430) [0.39 (0.19, 0.76)]. Of note, by design, the level of smoking did not differ between our cases and controls. This study does not provide strong evidence that PheT is a biomarker of pancreatic cancer susceptibility independent of dietary intake and select metabolism SNPs among a nonsmoking population.

Abstract Exposure to polycyclic aromatic hydrocarbons (PAHs), a byproduct of incomplete combustion, and its effects on the development of cancer needs further evaluation. Recent studies have analyzed the relationship between PAHs and tobacco or dietary intake in the form of processed foods and smoked/well-done meats. This study aims to assess the association of a blood biomarker and metabolite of PAHs, r-1-,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), selected metabolism SNPs, and pancreatic cancer. Demographics, food-frequency data, SNPs, treatment history and levels of PheT in plasma were collected from 400 participants (202 cases and 198 control) and evaluated based on pancreatic adenocarcinoma diagnosis. A two-stage analysis was completed to identify 1) SNPs that were significantly associated with pancreatic cancer and 2) Dietary intake and PheT variables significantly associated with pancreatic cancer. A univariate analysis for variables with OR≠1 and p-value &lt; 0.05 suggests significant relationship with pancreatic cancer and were carried forward to a multiple regression model for either food items or SNPs. Backward stepwise selection was used to eliminate non-significant variables. A collection of 5 SNPs were observed to form several of the most significant (adjusted p-value &lt;0.05) interaction pairs across different SNP models. These were rs566979 (gene: CAT), rs28540420 (gene: PTGER4), rs12029406 (gene: none), rs730368 (gene: PTGER4), and rs3181077 (gene: CCR1). A final multiple regression model combined the significant food items and SNPs. Final significant factors associated with pancreatic cancer after backward selection included: Type 2 Diabetes [7.66 (3.46, 17.76)], corrected percent recovered version of the PAH (cPheT) [1.03 (1.02, 1.05)], very well done red meat [0.90 (0.84, 0.96)], recessive(rs12203582) [3.58 (1.50, 8.83)], recessive(rs56679) [0.25 (0.06, 0.80)], overdominant(rs3784605) [3.42 (1.81, 6.66)], overdominant(rs721430) [0.42 (0.21, 0.83)]. Of note by design, the level of smoking did not differ between our cases and controls. This study provides evidence that a metabolite PheT could be a biomarker of pancreatic cancer independent of dietary intake, smoking, and select metabolism SNPs. Citation Format: Sierra Nguyen, Heather Carlson, Andrea Yoder, William R. Bamlet, Ann L. Oberg, Gloria M. Peterson, Steven Hecht, Rick Jansen. Polycyclic aromatic hydrocarbons and pancreatic cancer: An analysis of blood biomarker PheT as an exposure identifier [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B005.