Transcriptome analysis in human blood as a biomarker TIGD3 expression also appeared to correlate with serum levels of p53. Furthermore, a posi- tive signiﬁcant correlation was found between dioxins/furans and DGAT2 expression, a gene involved in triglyceride synthesis. The func- tions of these two genes as described in litera- ture, however, do not indicate a relationship with environmental carcinogenesis. When we assessed the inﬂuence of sex on the correlations of gene expressions and bio- markers of exposure, early effect, or tumor markers, we observed substantial differences between females and males. The correlation proﬁle, as observed in males only, reﬂects the total population profile more than that of females only. This suggested unique correlation proﬁle in females includes signiﬁcant associa- tions of gene expression with mostly biomark- ers of early effect, such as SOD2 expression correlating with the number of cells with MN, the number of MN per 1,000 binucleated cells, and the serum level of CEA. CYP1B1 expres- sion correlated with CEA levels. In addition, DGAT2 expression correlated signiﬁcantly with blood measures of Pb and median COMET values. Differences in kinetics, dynamics, and biotransformation of xenobiotics between the sexes (Beierle et al. 1999; Schwartz 2003) may explain the differences observed in the present Harbor Antwerp study. These observations warrant more in- depth analysis of this effect in the future. In general, the contributions of MAPK, CREB, and PTEN to the cell circuitry involved in carcinogenesis are also comprehen- sively summarized by Hanahan and Weinberg (2000) in their review on the essential altera- tions in cell physiology that establish malig- nant growth. Furthermore, observed effects on CXCL1 may be linked with the process of environmental carcinogenesis. These gene expression markers appear promising in their qualitative use because of their biologically relevant modes of action and consequential broadening of the insights into cancer risks due to environmental carcinogen exposure. We therefore suggest that the observed dose– response relationships between these modiﬁed gene expressions and well-known environ- mental carcinogens as present in the Flemish population deepen our understanding in envi- ronmental cancer risks and clearly present the value of gene expression analysis as a tool for biological monitoring purposes. In a few previous studies, gene expres- sion has also been monitored in peripheral blood from human populations. Wu et al. (2003) described gene expression proﬁling in a Taiwanese population exposed to arsenic this MAP kinase, ATF2, MEF2C, MAX, CDC25B, and p53, it is suggested to be associ- ated with stress-related transcription and cell cycle regulation, as well as genotoxic stress response (Cuenda and Rousseau 2007). MAPK is also known for its extensive role in cell differentiation and proliferation, as well as its involvement in the SOS-Ras-Raf-MAPK cascade, which plays a central role in acquired growth signal autonomy, considered a key event on the route of cell normalcy to malig- nancy, and at other levels of the carcinogenic process (Cuenda and Rousseau 2007; Hanahan and Weinberg 2000). PINK1 expres- sion correlated signiﬁcantly with endogenous levels of PCBs and p,p´-DDE. PINK1 is a PTEN-induced putative kinase. PTEN is a tumor suppressor, functioning as an inhibitor of the AKT/PKB signaling pathway, and is mutated in a large number of cancers (Kim and Mak 2006). CXCL1 is a chemokine whose gene expression was found in the present study to correlate signiﬁcantly with blood measures of dioxins and furans. It has been associated with tumor growth and metastasis (Wang et al. 1998). TIGD3 expression, a gene encoding a DNA-transposable element, correlated signiﬁ- cantly with the blood or urinary measures of PCBs and with 1-OH-pyrene in urine. Gent 0.8 0.6 0.4 tC0.2 ΔΔ0.0 –0.2 –0.4 –0.6 0.8 0.6 0.4 tC0.2 ΔΔ0.0 –0.2 –0.4 –0.6 0.8 0.6 0.4 tC 0.2 ΔΔ 0.0 –0.2 –0.4 –0.6 0.8 0.6 0.4 tC 0.2 ΔΔ 0.0 –0.2 –0.4 –0.6 1B F4TA 14KPA 2SOD 1LXCC 2TDGA I3TG 1PK 1YP D IN C M Antwerp Antwerp harbor Gent Gent harbor Rural Olen Canal Fruit Incinerators Incinerators 1B F4TA 14KPA 2SOD 1LXCC 2TGDA I3TG 1PK 1YP D IN C M 11B 4FT 14A 2SOD 1LXCC 2TDGA I3TG 1PK YPC A PKM D IN 11B 4FT 14A 2SOD 1LXCC 2TDGA I3TG 1PK YPC A PKM D IN Figure 1. Gene expression (mean ± SE) per region, relative to the total population averages, for all nonsmokers (former and never-smokers). Fruit, fruit cultivation region. Environmental Health Perspectives • VOLUME 116 | NUMBER 11 | November 2008 1523 1B F4TA 14KPA 2SOD 1LXCC 2TDGA I3TG 1PK 1YP D IN C 1B F4TA 14KPA 2SOD 1LXCC 2TDGA I3TG 1PK 1YP D IN C M M Rural Fruit 0.8 0.6 0.4 tC 0.2 ΔΔ 0.0 –0.2 –0.4 –0.6 0.8 0.6 0.4 tC 0.2 ΔΔ0.0 –0.2 –0.4 –0.6 0.8 0.6 0.4 tC0.2 ΔΔ0.0 –0.2 –0.4 –0.6 0.8 0.6 0.4 tC 0.2 ΔΔ0.0 –0.2 –0.4 –0.6 Olen 1B F4TA 14KPA 2SOD 1LXCC 2TDGA I3TG 1PK 1YP D IN C M Canal 11PB 4FTA 14 2D 1L 2T 3 1 YC KPAM SO XCC ADG ITDG IPKN