title: Interactions between oral contraceptive status and GSTM1 and GSTT1 deletions on insulin-like growth factor-1 (IGF-1) plasma levels in young healthy women.
abstract: OBJECTIVE
  Insulin-like growth factor-1 (IGF-1) is essential for the pubertal growth spurt and for normal mammary gland development. IGF-1 increases premenopausal breast cancer risk. Oral contraceptives (OCs) decrease IGF-1 in most women. The endogenous estrogens and their metabolites also influence IGF-1 levels. Glutathione S-transferases (GSTs) are involved in estrogen metabolism. We aimed to study IGF-1 levels and body size in relation to GSTM1 and GSTT1 deletions, and GSTP1*1B and current oral contraceptive (OC) status.
  
  
  METHODS
  Questionnaires on reproductive factors and OC use were completed and blood samples were obtained during menstrual cycle day 18-23 in healthy women (≤40 years) from breast cancer high-risk families. IGF-1 was analyzed with radioimmunoassay. Genetic analyses were done with PCR based methods. Initially 258 women were included. After exclusion 229 women were finally included in the analyses of IGF-1 in relation to GSTM1 and GSTT1.
  
  
  RESULTS
  Among the 142 non-OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with lower IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had higher IGF-1 levels (P(interaction)=0.024). In the 87 OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with higher IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had lower IGF-1 levels (P(interaction)=0.010). Among all 229 women, a three-way interaction model showed an interaction between the GSTM1*0/*0/GSTT1*0/*0 genotype and OC use on IGF-1 levels (P(interaction)=0.003). GSTP1*1B was not associated with IGF-1. The GSTM1*1/GSTT1*0/*0 genotype was associated with high body weight (P=0.003) and GSTM1*0/*0/GSTT1*0/*0 was associated with early growth (P=0.003).
  
  
  CONCLUSIONS
  Both OC use and GSTT1 and GSTM1 genotypes may influence IGF-1 levels. Further studies are warranted to confirm our finding and elucidate the clinical importance.
authors.affiliation: Department of Oncology, Clinical Sciences, Lund University, Sweden.
authors.forename: M C K
authors.initials: MC
authors.lastname: Henningson
authors.forename: M
authors.initials: M
authors.lastname: Hietala
authors.forename: E
authors.initials: E
authors.lastname: Bågeman
authors.forename: H
authors.initials: H
authors.lastname: Olsson
authors.forename: H
authors.initials: H
authors.lastname: Jernström
mesh_terms: D000328:Adult; D000465:Algorithms; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006262:Health; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D003276:Contraceptives, Oral; D005982:Glutathione Transferase; D007334:Insulin-Like Growth Factor I; C413545:glutathione S-transferase T1