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

Overview

Journal Menopause

Specialty Gynecology & Obstetrics

Date 2014 Jan 23

PMID 24448104

Citations 10

Authors

Samantha F Butts

Mary D Sammel

Christine Greer

Timothy R Rebbeck

David W Boorman

Ellen W Freeman

Affiliations

Soon will be listed here.

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.

Citing Articles

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Age of Natural Menopause Among Jordanian Women and Factors Related to Premature and Early Menopause.

Bustami M, Matalka K, Elyyan Y, Hussein N, Hussein N, Abu Safieh N Risk Manag Healthc Policy. 2021; 14:199-207.

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Genetic Variation and Hot Flashes: A Systematic Review.

Crandall C, Diamant A, Maglione M, Thurston R, Sinsheimer J J Clin Endocrinol Metab. 2020; 105(12).

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