Association between polycyclic aromatic hydrocarbon-DNA adduct levels in maternal and newborn white blood cells and glutathione S-transferase P1 and CYP1A1 polymorphisms
Rm. Whyatt et al., Association between polycyclic aromatic hydrocarbon-DNA adduct levels in maternal and newborn white blood cells and glutathione S-transferase P1 and CYP1A1 polymorphisms, CANC EPID B, 9(2), 2000, pp. 207-212
Polgcyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollut
ants; a number are carcinogenic. Metabolic polymorphisms may modulate susce
ptibility to PAM-induced DNA damage and carcinogenesis. This study investig
ates the relationship between PAH-DNA adduct levels (in maternal and newbor
n WBCs) and two polymorphisms: (a) an MspI RFLP in the 3' noncoding region
of cytochrome P4501A1 (CYP1A1); and (b) an A-->G transition in nucleotide 3
13 of glutathione S-transferase PI (GSTP1), resulting in an ile105val subst
itution, CYP1A1 catalyzes the bioactivation of PAH; the CYP1A1 MspI RFLP ha
s been associated with cancer of the lung, GSTP1 catalyzes the detoxificati
on of PAH; the Pa1 allele has greater catalytic efficiency toward PAH diol
epoxides, The study involves 160 mothers and their newborns from Poland. Re
gression models controlled for maternal smoking and other confounders. No a
ssociation was seen between maternal adduct levels and either polymorphism,
separately or combined, However, adduct levels were higher among newborns
with the CYP1A1 MspI restriction site (heterozygotes and homozygotes combin
ed) compared with newborns lacking the restriction site (P = 0.06), Adducts
were higher among GSTP1 ile/val and ile/ile newborns compared with GSTP1 v
al/val newborns (P = 0.08), Adduct levels were 4-fold higher among GSTP1 il
e/ile newborns having the CYP1A1 restriction site compared with GSTP1 val/v
al newborns who lacked the CYP1A1 restriction site (P = 0.04), This study d
emonstrates a significant combined effect of phase I and phase II polymorph
isms on DNA damage from PAHs in fetal tissues. It illustrates the importanc
e of considering interindividual variation in assessing risks of transplace
ntal exposure to PAHs.