Abstract B32: Levels of metabolites of naphthalene in urine predict translocations in peripheral blood lymphocytes in children

Chromosomal aberrations (CAs) and translocations (TRNS) (subtype of CAs) are a validated biomarker of increased cancer risk in adults. Prenatal exposure to semi-volatile air PAH predicts levels of stable CAs in neonatal (cord) blood. Urinary levels of 1 and 2 naphthol, metabolites of naphthalene, an IARC class2b possible carcinogen, appear elevated in the CCCEH birth cohort. We hypothesize that concurrent exposure to naphthalene is associated with development of CAs and TRNS in children. Whole blood from 113 five year old children (68 girls) participating in the CCCEH birth cohort composed of Dominican (DomAm) (N=66) and African-Americans (AfrAm) (N=47) was processed fresh for Whole Chromosome Paint (WCP)-Fluorescent In Situ Hybridization using WCP for chromosomes 1-6. 400 Cell Equivalents [CE]) were scored for each child. TRNS were scored in accordance with the PAINT convention and frequencies were expressed per 100 CE. Levels of PAH metabolites were measured using MSGC in spot urine samples (Sjodin laboratory, CDC) collected concurrently and adjusted for urine specific gravity (SG). We examined predictors of presence of CA9s or TRNS. For predicting frequency of CA and TRNS, mean ratios were derived for doubling of naphthol levels using negative binomial models. Results: 35 children had CA9s and 20 had TRNS. Geometric means among AfrAm were 3490.2 for 1naphthol, and 3005.1 for 2naphthol, and 3336.4 and 5256.6 for 1 & 2naphthol in DomAm children. Levels of 1& 2 napthol did not vary with presence of a smoker in the child9s home. 2naphthol (but not 1napthol) was higher in girls (p= 0.08) and in DomAm (p=0.01). After adjusting for gender and ethnicity, presence of both CA9s and TRNS was predicted by increasing levels of 1- and 2- naphthol: OR for presence of CA9s with increasing 1naphthol: (1.23; 95%CI:1.01, 1.48); and with 2napthol (1.19; 0.90, 1.56), but the effect was significantly higher in DomAms for both 1naphthol (1.63;1.21, 2.19) & 2naphthol (1.44; 1.02, 2.04). For TRNS, the OR was 1.55 (1.11,2.17) for 1naphthol, and 1.92 (1.20-3.08) for 2naphthol. Frequency of CA9s was predicted by 1naph (MR1.38; 1.10, 1.72) in DomAm but not in AfrAm (RR0.90; 0.65, 1.25). The association between naphthols and frequency of TRNS did not differ by ethnicity. To examine possible dose-response, levels of 2naphthol were grouped into tertiles using the lowest tertile as the referent group. After adjusting for gender/ethnicity, the proportion with TRNS present increased with increasing 2naphthol (though trend p = 0.09). Children with 2napthol in the highest tertile were significantly more likely to have translocations (OR 4.29; 95% CI: 1.11-16.55) when compared with children in the lowest tertile. Similarly, children with increasing 2-naphthol levels had increasing frequency of TRNS though the overall trend was not significant: mean TRNS frequencies for children in the highest tertile of exposure had a ratio of 3.23; (95%CI: 0.85-12.50) compared with those in the lowest tertile. The effect of increasing naphthol on aberrations or translocations was not dominated by any one chromosome, in contrast to our findings in newborns and prenatal air-PAH. Together these findings support our earlier findings that PAH exposure is associated with formation of TRNS, and suggests a dose response pattern with exposure to naphthalene, and an ethnic difference in susceptibility to formation of CAs. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B32.