Metabolites of the Polycyclic Aromatic Hydrocarbon Phenanthrene in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer.
Results from the Multiethnic Cohort Study demonstrated significant differences in lung cancer risk among cigarette smokers from five different ethnic/racial groups. For the same number of cigarettes smoked, and particularly among light smokers, African Americans and Native Hawaiians had the highest risk for lung cancer, Whites had intermediate risk, while Latinos and Japanese Americans had the lowest risk. We analyzed urine samples from 331-709 participants from each ethnic group in this study for metabolites of phenanthrene, a surrogate for carcinogenic polycyclic aromatic hydrocarbon exposure. Consistent with their lung cancer risk and our previous studies of several other carcinogens and toxicants of cigarette smoke, African Americans had significantly (p<0.0001) higher median levels of the two phenanthrene metabolites 3-hydroxyphenanthrene (3-PheOH, 0.931 pmol/ml) and phenanthrene tetraol (PheT, 1.13 pmol/ml) than Whites (3-PheOH, 0.697 pmol/ml; PheT, 0.853 pmol/ml) while Japanese-Americans had significantly (p = 0.002) lower levels of 3-PheOH (0.621 pmol/ml) than Whites. PheT levels (0.838 pmol/ml) in Japanese-Americans were not different from those of Whites. These results are mainly consistent with the lung cancer risk of these three groups, but the results for Native Hawaiians and Latinos were more complex. We also carried out a genome wide association study in search of factors that could influence PheT and 3-PheOH levels. Deletion of GSTT1 explained 2.2% of the variability in PheT, while the strongest association, rs5751777 (p = 1.8x10-62) in the GSTT2 gene, explained 7.7% of the variability in PheT. These GWAS results suggested a possible protective effect of lower GSTT1 copy number variants on the diol epoxide pathway, which was an unexpected result. Collectively, the results of this study provide further evidence that different patterns of cigarette smoking are responsible for the higher lung cancer risk of African Americans than of Whites and the lower lung cancer risk of Japanese Americans, while other factors appear to be involved in the differing risks of Native Hawaiians and Latinos.
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, United States of America.
Yesha M
YM
Patel
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, United States of America.
Sungshim L
SL
Park
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, United States of America.
Steven G
SG
Carmella
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, United States of America.
Viviana
V
Paiano
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, United States of America.
Natalie
N
Olvera
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, United States of America.
Daniel O
DO
Stram
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, United States of America.
Christopher A
CA
Haiman
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, United States of America.
Loic
L
Le Marchand
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, United States of America.
Stephen S
http://orcid.org/0000-0001-7228-1356
SS
Hecht
D000368:Aged; D005260:Female; D018628:Gene Dosage; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics / Q000652:urine; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010616:Phenanthrenes / Q000652:urine*; D012307:Risk Factors; D012907:Smoking / Q000208:ethnology / Q000235:genetics / Q000378:metabolism / Q000652:urine
D009363:Neoplasm Proteins; D010616:Phenanthrenes; C491107:GSTT2 protein, human; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase