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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Cigarettes, genetic background, and menopausal timing: the presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers
Menopause (New York, N.Y.), v 21(7), pp 694-701
Jul 2014
PMID: 24448104
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objective: This study aims to evaluate associations between variations in genes involved in the metabolism of environmental chemicals and steroid hormones and risk of menopause in smokers.
Methods: Survival analysis was performed on 410 eligible participants from the Penn Ovarian Aging study (ongoing for 14 years), a cohort study of late-reproductive-age women. Single nucleotide polymorphisms at the following loci were studied: COMT Val158Met, CYP1B1*4 Asn452Ser, CYP1B1*3 Leu432Val, and CYP3A4*1B.
Results: Significant interactions between smoking and single nucleotide polymorphisms were observed in European-American carriers of CYP3A4*1B and CYP1B1*3, supporting a greater risk of menopause entry compared with those not carrying these alleles. Among CYP1B1*3 carriers, smokers had a greater risk of menopause entry than nonsmokers (adjusted hazard ratio [HR], 2.26; 95% CI, 1.4-3.67; median time to menopause, 10.42 and 11.07 y, respectively). No association between smoking and menopause was identified in CYP1B1 wild types. Among CYP3A4*1B carriers, smokers were at greater risk for menopause entry than nonsmokers (adjusted HR, 15.1; 95% CI, 3.31-69.2; median time to menopause, 11.36 and 13.91 y, respectively). Risk of menopause entry in CYP3A4 wild types who smoked was far lower (adjusted HR, 1.59; 95% CI, 1.03-2.44). Heavily smoking CYP1B1*3 carriers (adjusted HR, 3.0; 95% CI, 1.54-5.84; median time to menopause, 10.41 y) and heavily smoking CYP3A4*1B carriers (adjusted HR, 17.79; 95% CI, 3.21-98.65; median time to menopause, 5.09 y) had the greatest risk of menopause entry.
Conclusions: Our finding that the risk of menopause entry in European-American smokers varies depending on genetic background represents a novel gene-environment interaction in reproductive aging.
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Details
- Title
- Cigarettes, genetic background, and menopausal timing: the presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers
- Creators
- Samantha F. Butts - University of PennsylvaniaMary D. Sammel - Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USAChristine Greer - University of MiamiTimothy R. Rebbeck - Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USADavid W. Boorman - Drexel Univ, Sch Med, Philadelphia, PA 19104 USAEllen W. Freeman - Univ Penn, Dept Obstet & Gynecol, Perelman Sch Med, Philadelphia, PA 19104 USA
- Publication Details
- Menopause (New York, N.Y.), v 21(7), pp 694-701
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 8
- Grant note
- RR024134 / Perelman School of Medicine Translational and Clinical Research Center P30ES013508 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) R01AG012745 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) Perelman School of Medicine Center of Excellence for Diversity R01-AG-12745 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 5P30ES013508-07 / National Institute of Environmental Health Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) UL1RR024134 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:000338539400004
- Scopus ID
- 2-s2.0-84903149914
- Other Identifier
- 991021887712904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Obstetrics & Gynecology