Abstract
Epidemiologic studies have linked tobacco-related cancer risk to an altered ability to metabolize carcinogenic or addictive compounds along well-characterized pathways. We hypothesized that maternal(m) or fetal(f) genotypes which alter activity along such pathways may account for varying susceptibility to adverse pregnancy outcomes among smokers, and thus sought to determine the association between functional polymorphisms in CYP1A1, GSTT1, and CYP2A6 and these outcomes. Blinded genotyping was perfomed from prospectively obtained banked DNA samples for known functional allelic variants of CYP1A1(Ile462ValAA>AG/GG), GSTT1(del), and CYP2A6(Lys160HisT>A) in 502 smokers, 502 contols, and their conceptuses. Associations between smoking and genotype in relation to individual and a composite outcome [SGA <10%, fetal loss, preterm birth (PTB), and abruption] and birthweight were evaluated. The overall relative risk of adverse composite outcome among tobacco users (RR1.2, p=.04) was modified in a genotype-specific fashion: increased risk occurred among GSTT1del (RRf1.7, p=.07; RRm1.9, p=.01) while maternal CYP2A6AT trended towards a protective effect (RRm.69, p=.47); CYP1A1AA>AG/GG trended towards modified risk (RRf1.8, p=.27; RRm1.8, p=.10). The overall risk of smoking for SGA (RR1.7, p=.006) was increased with fetal but not maternal GSTT1del (RRf3.4, p=.02). Considering birthweight as a continuous variable after adjustment for gestational age in a linear model, the mean birthweight of tobacco-exposed fetuses with GSTT1del was reduced by 291g (p<.0001), whereas tobacco-exposed fetuses without the GSTT1(del) were unaffected (mean reduction 56g, p=0.22). Metabolic gene polymorphisms alter tobacco-related risk of adverse pregnancy outcomes. The inability to excrete reactive intermediates (GSTT1del), increased ability to form carcinogenic adducts (CYP1A1Ile462Val), or altered nicotine metabolism(CYP2A6Lys160His) may explain varying susceptibility to in utero tobacco exposure.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
