A cross-sectional study of polycyclic aromatic hydrocarbon-DNA adducts and polymorphism of glutathione S-transferases among heavy smokers by race/ethnicity.
Differences in lung cancer risk by race/ethnicity have been observed among smokers. To determine whether these observations might reflect differences in the formation of carcinogen-DNA adducts, we analysed blood specimens (n=151) collected from smokers who were recruited for possible participation in an antioxidant vitamin intervention study. Mononuclear cells were analysed for polycyclic aromatic hydrocarbon (PAH)-DNA adducts by competitive enzyme-linked immunosorbent assay. Genotypes of glutathione S-transferase M1 and P1 (GSTM1 and GSTP1), enzymes involved in the detoxification of PAH metabolites, were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively. GSTM1 was present in 65 out of 88 (73.4%), 16 out of 32 (50.0%) and 16 out of 29 (54.8%) of African-Americans, Caucasians and Latinos, respectively (p=0.022). Homozygosity for the GSTP1 codon 105 variant was found in 25.6%, 6.3% and 10.0% of African-Americans, Caucasians and Latinos, respectively (p=0.023). Regression analysis of the log-transformed adduct levels confirmed that Caucasian and Latino subjects had lower PAH-DNA adduct levels than African-American subjects, after adjustment for gender, education, alpha-tocopherol and beta-carotene levels, and GSTM1 status. Further adjustment for age and current smoking habits had no impact on these findings. Although crude analysis suggested that the GSTM1-positive genotype may be associated with lower PAH-DNA levels in Caucasians (but not in African-Americans or Latinos), a formal test for interaction between GSTM1 and ethnicity was not significant. We found no association between adduct levels and GSTP1 genotype. Although the mechanism is unclear, ethnic differences in DNA damage levels may in part explain why African-Americans have higher lung cancer incidence rates than other ethnic groups.
Weiserbs
Kera F
KF
Department of Epidemiology Mailman School of Public Health of Columbia University New York, NY 10032, USA.
Jacobson
Judith S
JS
Begg
Melissa D
MD
Wang
Lian Wen
LW
Wang
Qiao
Q
Agrawal
Meenaksh
M
Norkus
Edward P
EP
Young
Tie-Lan
TL
Santella
Regina M
RM
D000328:Adult; D001741:Black or African American; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000097:blood; D003367:Cotinine / Q000097:blood; D003430:Cross-Sectional Studies; D018736:DNA Adducts / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005006:Ethnicity; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006630:Hispanic or Latino; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012907:Smoking / Q000378:metabolism*; D011795:Surveys and Questionnaires; D014810:Vitamin E / Q000097:blood; D044465:White People; D019207:beta Carotene / Q000097:blood
D000975:Antioxidants; D001205:Ascorbic Acid; D003367:Cotinine; D018736:DNA Adducts; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; D011084:Polycyclic Aromatic Hydrocarbons; D014810:Vitamin E; D019207:beta Carotene; C496556:GSTP1 protein, human