Person:

Michels, Karin

There is growing interest in identifying surrogate tissues to identify epimutations in cancer patients since primary target tissues are often difficult to obtain. Methylation patterns at imprinted loci are established during gametogenesis and post fertilization and their alterations have been associated with elevated risk of cancer. Methylation at several imprinted differentially methylated regions (GRB10 ICR, H19 ICR, KvDMR, SNRPN/SNURF ICR, IGF2 DMR0, and IGF2 DMR2) were analyzed in DNA from leukocytes and mammary tissue (normal, benign diseases, or malignant tumors) from 87 women with and without breast cancer (average age of cancer patients: 53; range: 31–77). Correlations between genomic variants and DNA methylation at the studied loci could not be assessed, making it impossible to exclude such effects. Methylation levels observed in leukocyte and mammary tissue DNA were close to the 50% expected for monoallellic methylation. While no correlation was observed between leukocyte and mammary tissue DNA methylation for most of the analyzed imprinted genes, Spearman's correlations were statistically significant for IGF2 DMR0 and IGF2 DMR2, although absolute methylation levels differed. Leukocyte DNA methylation levels of selected imprinted genes may therefore serve as surrogate markers of DNA methylation in cancer tissue.

Background: In the absence of clinical trial data, large post-marketing observational studies are essential to evaluate the safety and effectiveness of medications during pregnancy. We identified a cohort of pregnancies ending in live birth within the 2000–2007 Medicaid Analytic eXtract (MAX). Herein, we provide a blueprint to guide investigators who wish to create similar cohorts from healthcare utilization data and we describe the limitations in detail. Methods: Among females ages 12–55, we identified pregnancies using delivery-related codes from healthcare utilization claims. We linked women with pregnancies to their offspring by state, Medicaid Case Number (family identifier) and delivery/birth dates. Then we removed inaccurate linkages and duplicate records and implemented cohort eligibility criteria (i.e., continuous and appropriate enrollment type, no private insurance, no restricted benefits) for claim information completeness. Results: From 13,460,273 deliveries and 22,408,810 child observations, 6,107,572 pregnancies ending in live birth were available after linkage, cleaning, and removal of duplicate records. The percentage of linked deliveries varied greatly by state, from 0 to 96%. The cohort size was reduced to 1,248,875 pregnancies after requiring maternal eligibility criteria throughout pregnancy and to 1,173,280 pregnancies after further applying infant eligibility criteria. Ninety-one percent of women were dispensed at least one medication during pregnancy. Conclusions: Mother-infant linkage is feasible and yields a large pregnancy cohort, although the size decreases with increasing eligibility requirements. MAX is a useful resource for studying medications in pregnancy and a spectrum of maternal and infant outcomes within the indigent population of women and their infants enrolled in Medicaid. It may also be used to study maternal characteristics, the impact of Medicaid policy, and healthcare utilization during pregnancy. However, careful attention to the limitations of these data is necessary to reduce biases.