title: Variation in inflammatory cytokine/growth-factor genes and mammographic density in premenopausal women aged 50-55.
abstract: BACKGROUND
  Mammographic density (MD) has been found to be an independent risk factor for breast cancer. Although data from twin studies suggest that MD has a strong genetic component, the exact genes involved remain to be identified. Alterations in stromal composition and the number of epithelial cells are the most predominant histopathological determinants of mammographic density. Interactions between the breast stroma and epithelium are critically important in the maturation and development of the mammary gland and the cross-talk between these cells are mediated by paracrine growth factors and cytokines. The potential impact of genetic variation in growth factors and cytokines on MD is largely unknown.
  
  
  METHODS
  We investigated the association between 89 single nucleotide polymorphisms (SNPs) in 7 cytokine/growth-factor genes (FGFR2, IGFBP1, IGFBP3, TGFB1, TNF, VEGF, IL6) and percent MD in 301 premenopausal women (aged 50 to 55 years) participating in the Norwegian Breast Cancer Screening Program. We evaluated the suggestive associations in 216 premenopausal Singapore Chinese Women of the same age.
  
  
  RESULTS
  We found statistically significant associations between 9 tagging SNPs in the IL6 gene and MD in Norwegian women; the effect ranged from 3-5% in MD per variant allele (p-values = 0.02 to 0.0002). One SNP in the IL6 (rs10242595) significantly influenced MD in Singapore Chinese women.
  
  
  CONCLUSIONS
  Genetic variations in IL6 may be associated with MD and therefore may be an indicator of breast cancer risk in premenopausal women.
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.
authors.forename: Ali
authors.initials: A
authors.lastname: Ozhand
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.forename: Anna H
authors.initials: AH
authors.lastname: Wu
authors.forename: Merete
authors.initials: M
authors.lastname: Ellingjord-Dale
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.forename: Roberta
authors.initials: R
authors.lastname: McKean-Cowdin
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
mesh_terms: D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D000071060:Breast Density; D001943:Breast Neoplasms / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D055088:Early Detection of Cancer; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D042361:Mammary Glands, Human / Q000002:abnormalities*; D008875:Middle Aged; D009664:Norway; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017697:Premenopause / Q000235:genetics*; D012846:Singapore
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6