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000167224 0247_ $$2doi$$a10.1038/s41416-020-01185-w
000167224 0247_ $$2pmid$$apmid:33495599
000167224 0247_ $$2ISSN$$a0007-0920
000167224 0247_ $$2ISSN$$a1532-1827
000167224 0247_ $$2altmetric$$aaltmetric:98783705
000167224 037__ $$aDKFZ-2021-00209
000167224 041__ $$aeng
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000167224 1001_ $$00000-0002-8230-5662$$aJohnson, Nichola$$b0
000167224 245__ $$aCYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.
000167224 260__ $$aEdinburgh$$bNature Publ. Group$$c2021
000167224 3367_ $$2DRIVER$$aarticle
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000167224 3367_ $$2BibTeX$$aARTICLE
000167224 3367_ $$2ORCID$$aJOURNAL_ARTICLE
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000167224 500__ $$a2021 Feb;124(4):842-854
000167224 520__ $$aEpidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk.We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry.For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10-8).The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
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