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Polymorphisms in the estrogen receptor alpha gene (ESR1), daily cycling estrogen and mammographic density phenotypes

Permanent lenke
https://hdl.handle.net/10037/10771
DOI
https://doi.org/10.1186/s12885-016-2804-1
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article.pdf (625.7Kb)
(PDF)
Dato
2016-10-07
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Fjeldheim, Frøydis Nyborg; Frydenberg, Hanne; Flote, Vidar Gordon; McTiernan, Anne; Furberg, Anne-Sofie; Ellison, Peter T.; Barrett, Emily S.; Wilsgaard, Tom; Jasienska, Grazyna; Ursin, Giske; Wist, Erik; Thune, Inger
Sammendrag
Background: Single nucleotide polymorphisms (SNPs) involved in the estrogen pathway and SNPs in the estrogen receptor alpha gene (ESR1 6q25) have been linked to breast cancer development, and mammographic density is an established breast cancer risk factor. Whether there is an association between daily estradiol levels, SNPs in ESR1 and premenopausal mammographic density phenotypes is unknown. Methods: We assessed estradiol in daily saliva samples throughout an entire menstrual cycle in 202 healthy premenopausal women in the Norwegian Energy Balance and Breast Cancer Aspects I study. DNA was genotyped using the Illumina Golden Gate platform. Mammograms were taken between days 7 and 12 of the menstrual cycle, and digitized mammographic density was assessed using a computer-assisted method (Madena). Multivariable regression models were used to study the association between SNPs in ESR1, premenopausal mammographic density phenotypes and daily cycling estradiol. Results: We observed inverse linear associations between the minor alleles of eight measured SNPs (rs3020364, rs2474148, rs12154178, rs2347867, rs6927072, rs2982712, rs3020407, rs9322335) and percent mammographic density (p-values: 0.002–0.026), these associations were strongest in lean women (BMI, ≤23.6 kg/m2.). The odds of abovemedian percent mammographic density (>28.5 %) among women with major homozygous genotypes were 3–6 times higher than those of women with minor homozygous genotypes in seven SNPs. Women with rs3020364 major homozygous genotype had an OR of 6.46 for above-median percent mammographic density (OR: 6.46; 95 % Confidence Interval 1.61, 25.94) when compared to women with the minor homozygous genotype. These associations were not observed in relation to absolute mammographic density. No associations between SNPs and daily cycling estradiol were observed. However, we suggest, based on results of borderline significance (p values: 0.025–0.079) that the level of 17β-estradiol for women with the minor genotype for rs3020364, rs24744148 and rs2982712 were lower throughout the cycle in women with low (<28.5 %) percent mammographic density and higher in women with high (>28.5 %) percent mammographic density, when compared to women with the major genotype.
Beskrivelse
Published version. Source at http://doi.org/10.1186/s12885-016-2804-1. License CC BY 4.0.
Forlag
BioMed Central
Sitering
Fjeldheim FN, Frydenberg H, Flote VG, McTiernan A, Furberg AS, Ellison PT, Barrett ES, Wilsgaard T, Jasienska G, Ursin G, Wist E, Thune I. Polymorphisms in the estrogen receptor alpha gene (ESR1), daily cycling estrogen and mammographic density phenotypes. BMC Cancer. 2016;16:776:1-12
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