title: Estrogen pathway polymorphisms and mammographic density.
abstract: Elevated mammographic density (MD) is strongly associated with breast cancer risk and the estrogen pathway has been proposed as a potential mechanism for this association. It has been repeatedly observed that several established estrogen-related factors associated with breast cancer risk, such as parity and hormone replacement therapy, are also associated with MD. However, the association of circulating estrogen levels (known to be strongly positively associated with breast cancer risk) with MD has so far been inconsistent. Since MD is highly heritable, single nucleotide polymorphisms (SNPs) in genes involved in the estrogen pathway and their relation with MD could provide information that would help understand the link between MD and breast cancer risk. This review of 18 studies describes the relation of SNPs located in genes of the estrogen pathway (genes coding for hydroxysteroid dehydrogenases (HSD3B1, HSD17B1), cytochrome P450 (CYP1A1, CYP1A2, CYP17A1, CYP19A1 and CYP1B1), catechol-O-methyltransferase (COMT), uridine diphospho-glucuronosyltransferase (UGT1A1), sulfotransferases (SULT1A1, SULT1E1) and for estrogen receptors alpha and beta (ESR1, ESR2)) with MD. Most of the SNPs evaluated showed no association with MD when analyses were performed on overall study population. However, when this relation was assessed within strata based on estrogen-related factors, a few SNPs (HSD17B1 (rs2010750, rs598126 and rs676387), COMT (rs4680), UGT1A1 (rs8175347) and ESR1 (rs9340799)) seemed to be related to MD in the same direction of their associations with breast cancer risk. Since such data are very limited, additional research including stratified analyses by factors related to estrogen are needed to validate these findings.
authors.affiliation: Population Health Research Unit, FRSQ Research Center of the Quebec University Affiliated Hospital Center, Quebec City, QC, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dumas
authors.forename: Caroline
authors.initials: C
authors.lastname: Diorio
mesh_terms: D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D008327:Mammography / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000235:genetics; D012306:Risk; D015238:Sulfotransferases / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D002394:Catechol O-Methyltransferase; D003577:Cytochrome P-450 Enzyme System; D004967:Estrogens; D014453:Glucuronosyltransferase; D006913:Hydroxysteroid Dehydrogenases; D011960:Receptors, Estrogen; D015238:Sulfotransferases; D000099148:UGT1A1 Enzyme