RT Journal Article SR Electronic T1 Global Gene Expression Analysis in Cord Blood Reveals Gender-Specific Differences in Response to Carcinogenic Exposure In Utero JF Cancer Epidemiology Biomarkers & Prevention JO Cancer Epidemiol Biomarkers Prev FD American Association for Cancer Research DO 10.1158/1055-9965.EPI-12-0304 A1 Hochstenbach, Kevin A1 van Leeuwen, Danitsja M. A1 Gmuender, Hans A1 Gottschalk, Ralf W. A1 Løvik, Martinus A1 Granum, Berit A1 Nygaard, Unni A1 Namork, Ellen A1 Kirsch-Volders, Micheline A1 Decordier, Ilse A1 Vande Loock, Kim A1 Besselink, Harrie A1 Törnqvist, Margareta A1 von Stedingk, Hans A1 Rydberg, Per A1 Kleinjans, Jos C.S. A1 van Loveren, Henk A1 van Delft, Joost H.M. YR 2012 UL http://cebp.aacrjournals.org/content/early/2012/09/07/1055-9965.EPI-12-0304.abstract AB Background: It has been suggested that fetal carcinogenic exposure might lead to predisposition to develop cancer during childhood or in later life possibly through modulation of the fetal transcriptome. Because gender effects in the incidence of childhood cancers have been described, we hypothesized differences at the transcriptomic level in cord blood between male and female newborns as a consequence of fetal carcinogenic exposure. The objective was to investigate whether transcriptomic responses to dietary genotoxic and nongenotoxic carcinogens show gender-specific mechanisms-of-action relevant for chemical carcinogenesis. Methods: Global gene expression was applied in umbilical cord blood samples, the CALUX-assay was used for measuring dioxin(-like), androgen(-like), and estrogen(-like) internal exposure, and acrylamide–hemoglobin adduct levels were determined by mass spectrometry adduct-FIRE-procedureTM. To link gene expression to an established phenotypic biomarker of cancer risk, micronuclei frequencies were investigated. Results: While exposure levels did not differ between sexes at birth, important gender-specific differences were observed in gene expressions associated with these exposures linked with cell cycle, the immune system and more general cellular processes such as posttranslation. Moreover, oppositely correlating leukemia/lymphoma genes between male and female newborns were identified in relation to the different biomarkers of exposure that might be relevant to male-specific predisposition to develop these cancers in childhood. Conclusions/Impact: This study reveals different transcriptomic responses to environmental carcinogens between the sexes. In particular, male-specific TNF-alpha-NF-kB signaling upon dioxin exposure and activation of the Wnt-pathway in boys upon acrylamide exposure might represent possible mechanistic explanations for gender specificity in the incidence of childhood leukemia. Cancer Epidemiol Biomarkers Prev; 1–12. ©2012 AACR.