LIFESTYLE FACTORS AFFECTING FETAL SOMATIC MUTATION

点击翻译按钮获取中文摘要

DESCRIPTION: (Adapted from Investigator's Abstract) Somatic mutations during embryonic/fetal life have prospective health implications. Early cancer-predisposing mutations in oncogenes, tumor suppressor genes, or genes involved in DNA repair may result in significant numbers of initiated mutant cells at birth due to clonal expansion during growth and development of the fetus. Clonal expansion of mutant cells during development can also result in mosaic expression of genes presenting as birth defects. Mutations occurring early in development can also be fixed in differentiating germ cells leading to gonadal mosaicism and the emergence of new Mendelian disorders. This study of 300 maternal/newborn pairs is designed to assess the impact of maternal environments on embryonic/fetal somatic mutation at two independent loci (HPRT and GPA) in placental blood cells. This proposed investigation follows the investigators' initial survey of somatic mutation in newborns in which they found that maternal exposure to tobacco smoke and lower socioeconomic status, perhaps because of its association with maternal lifestyle factors, appears to increase the frequency and alter the spectrum of the molecular mechanisms of somatic mutation in utero. Subjects will be recruited from an ethnically and socioeconomically diverse population of women at their first prenatal visit, typically at 10-14 weeks gestation. They will be interviewed and administered a comprehensive questionnaire to characterize their exposure to tobacco smoke and determine other demographic variables. Maternal blood samples will be obtained at initial interview, at 28-32 weeks of gestation, and at delivery. The blood samples from these mothers, together with placental blood samples from their newborns, will be assayed for 4-amino biphenyl hemoglobin (4-ABP-Hb) adducts to quantitate the biologically effective dose of tobacco smoke mutagens to the mother and fetus throughout gestation. HPRT and GPA mutant frequencies measured in placental blood samples will be tested for association with 4-ABP-Hb adduct levels, and other lifestyle/exposure variables. The molecular spectrum of HPRT mutations in the newborns will be analyzed for evidence of environmental exposures. Finally, GPA mutation frequencies in maternal/newborn pairs will be tested for association suggestive of shared gene/environment factors. The investigators state that this focused study will seek to confirm their preliminary findings in an independent population of mothers and newborns and to specifically ascertain whether the previously observed associations reflect the direct mutagenic effect of specific and identifiable maternal exposures.