Global Gene Expression Analysis in Cord Blood Reveals Gender-Specific Differences in Response to Carcinogenic Exposure In Utero

Global Gene Expression Analysis in Cord Blood Reveals Gender-Specific Differences in Response to Carcinogenic Exposure In Utero

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 difference...

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Bibliographic Details
Published in:Cancer epidemiology, biomarkers & prevention Vol. 21; no. 10; pp. 1756 - 1767
Main Authors: HOCHSTENBACH, Kevin, LEEUWEN, Danitsja M. Van, KIM VANDE LOOCK, BESSELINK, Harrie, TÖRNQVIST, Margareta, STEDINGK, Hans Von, RYDBERG, Per, KLEINJANS, Jos C. S, LOVEREN, Henk Van, DELFT, Joost H. M. Van, GMUENDER, Hans, GOTTSCHALK, Ralf W, LØVIK, Martinus, GRANUM, Berit, NYGAARD, Unni, NAMORK, Ellen, KIRSCH-VOLDERS, Micheline, DECORDIER, Ilse
Format: Journal Article
Language:English
Published: Philadelphia, PA American Association for Cancer Research 01-10-2012
Subjects:
Acrylamide - metabolism
Adult
Biological and medical sciences
Biomarkers
Carcinogens - toxicity
Estrogen Receptor alpha - genetics
Female
Fetal Blood - metabolism
Fetus - drug effects
Gene Expression Profiling
Humans
Male
Medical sciences
Micronuclei, Chromosome-Defective - statistics & numerical data
Pregnancy
Receptors, Androgen - genetics
Sex Characteristics
Signal Transduction
Tumors
Carcinogen
Cancerology
Sex
Fetus
Exposure
Umbilical cord
Gene expression
In utero
Comparative study
Blood
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Summary: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. 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-procedure(TM). To link gene expression to an established phenotypic biomarker of cancer risk, micronuclei frequencies were investigated. 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.
ISSN:1055-9965
1538-7755
1538-7755
DOI:10.1158/1055-9965.epi-12-0304