Abstract 1897: DNA methylation levels in specific imprinting control regions in children conceived with and without assisted reproductive technology (ART)

It is not known if children conceived through assisted reproductive technology (ART) might harbor subtle epigenetic disruptions which could lead to a predisposition to cancer either in childhood or adulthood. Evidence of an association between parental infertility treatment and childhood cancer has been inconsistent. However, a positive association between assisted reproductive technology (ART) and Beckwith-Wiedemann syndrome (BWS) has been seen in many studies. Disruptions of epigenetic mechanisms may be responsible for both the increase in imprinting disorders such as BWS and the suspected increased risk in childhood cancer. This clinical study examined potential differences in DNA methylation at genomic sites associated with BWS and certain cancers in non-syndromic children conceived either spontaneously or through ART. Mothers who conceived through ART and reported a live birth between March 2005 and December 2008 were recruited from the University of Minnesota Reproductive Medicine Center. Spontaneously conceived (SC) children born between March 2005 and December 2008 and their mothers were recruited through advertisement. Information about reproductive history, demographic factors, birth characteristics, and infertility treatment was obtained from maternal interview and medical records. Peripheral blood lymphocytes and buccal cell samples were collected from participating children. Methylation analysis was performed using pyrosequencing. Five specific gene regions were included (IGF2 DMR0, 3 rd and 6 th CTCF-binding sites of H19 DMR, IGF2R, and KvDMR). Statistical analysis of methylation differences was performed using linear regression with generalized estimating equations. Correlation between lymphocyte and buccal cell samples was assessed using Pearson9s correlation coefficient. A total of 67 ART children and 31 SC children contributed samples. No statistically significant difference between groups was found at any loci examined in lymphocytes. However, possible differences were found in buccal cell samples for IGF2 DMR0 (Difference: 2.33; 95% CI: -0.08, 4.82; p = 0.06) and IGF2R (Difference: -2.83; 95% CI: -5.88, 0.22; p = 0.07). Subgroup analysis indicated potentially lower methylation among children whose parents had unexplained infertility. Notably, correlation between lymphocyte and buccal cell samples was very low for all loci. Observed differences in methylation between the ART and SC groups were very small in the two tissues examined so it is unlikely that important differences were missed. Although no significant differences were found in this study, possible changes in methylation patterns could still exist at other loci and in other tissues. Additional clinical and epidemiological studies are needed to more fully examine the possible association between ART and childhood cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1897. doi:10.1158/1538-7445.AM2011-1897