Fetal growth and body size genes and risk of childhood acute lymphoblastic leukemia

作者：Chokkalingam Anand P^*; Metayer Catherine; Scelo Ghislaine; Chang Jeffrey S; Schiffman Joshua; Urayama Kevin Y; Ma Xiaomei; Hansen Helen M; Feusner James H; Barcellos Lisa F; Wiencke John K; Wiemels Joseph L; Buffler Patricia A

来源：Cancer Causes & Control, 2012, 23(9): 1577-1585.

DOI：10.1007/s10552-012-0035-6

• IGF
• Insulin-like growth factors
• Leukemia
• Childhood cancer
• Fetal growth

Accumulating evidence suggests that childhood acute lymphoblastic leukemia (ALL) may be initiated in utero or early in the postnatal period. High birth weight (or rapid fetal growth) is associated with risk of ALL, but the mechanisms are not understood. In a population-based epidemiologic study of childhood ALL, we utilized a haplotype-based approach to assess the role of eight genes involved in fetal growth and body size regulation in 377 childhood ALL cases and 448 controls. We found significant haplotype associations with risk of childhood ALL for IGF1 among non-Hispanics and Hispanics together (p = 0.002), for IGF2 among Hispanics (p = 0.040), and for IGF2R among Hispanics and non-Hispanics (p = 0.051 and 0.009, respectively). No haplotype associations were observed for IGF1R or the studied genes involved in body size regulation, including LEP, LEPR, GHRL, and NPY. Our study is the first to identify an association between the genes involved in the IGF axis and risk of childhood ALL. These findings for childhood ALL emphasize the importance of fetal growth, when lymphoid progenitor cells are not yet fully differentiated and therefore more susceptible to malignant transformation. Additional studies are needed to confirm these findings and identify specific causal variants.

• 出版日期2012-9