THE INFLUENCE OF IN UTERO MATERNAL AND CHILD FACTORS ON TELOMERE LENGTH AND POSSIBLE DIFFERENCES BY RACE: CLUES TO THE RACIAL DISPARITY IN PROSTATE CANCER

in utero;telomere;race;prostate cancer;Epidemiology

Weber, KariNavas-Acien, Ana ;

Johns Hopkins University

关键词: in utero;    telomere;    race;    prostate cancer;    Epidemiology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/39733/WEBER-DISSERTATION-2016.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

There is a pronounced racial disparity in prostate cancer risk and mortality. Modifiable factors in adulthood that explain the disparity have not been identified. Whether racial differences in utero may account for this disparity is understudied. Shorter telomeres have been associated with cancer, and telomere length (TL) at birth is hypothesized to set the trajectory for lifetime telomere shortening and influence adult disease risk including prostate cancer.TL is heritable but telomeres also shorten with cell replication and oxidative damage, and thus may serve as an indicator of cumulative exposure. We investigated the association of in utero maternal and neonate factors with cord blood TL, and whether TL differences between black and white male neonates, as a marker for inherent and exposure racial differences in utero, may explain some of the prostate cancer disparity. We also addressed whether TL differs by race in adult males. We used the Hormones in Umbilical Cord Blood Study (HUB) and Expanded HUB (EHUB) to evaluate whether TL differs by race in neonates, and to estimate associations between maternal and neonate factors and TL. We used the Health Professionals Follow-up Study (HPFS) to evaluate midlife racial differences and associations. In HUB, no factors were associated with TL, and TL did not differ by race. In EHUB, higher pre-pregnancy maternal BMI and less education were inversely associated with neonate TL. Black mothers and neonates had shorter telomeres compared to whites but adjustment for BMI and education eliminated this difference. Maternal and neonate TL were moderately positively correlated regardless of race and after adjustment for confounders. In HPFS, waist circumference, physical inactivity, and smoking were inversely associated with TL but TL did not differ by race before or after adjusting for these factors. Our hypotheses were not supported in HUB or HPFS but were in EHUB. In EHUB the maternal-neonate TL correlation suggests that TL may differ by race at birth due in part to inherent and, in part, racial differences in maternal factors. These findings inform the prostate cancer racial disparity and the influence of the in utero environment on offspring adult disease risk.