Assessing Endogenous and Exogenous Hormone Exposures and Breast Development in a Migrant Study of Bangladeshi and British Girls.

Renata E Howland,Lauren C Houghton,Nicole C Deziel,Osul A Choudhury,Stephen D Fox,Jonathan N Hofmann,Gillian R Bentley,Rebecca Troisi,Hormuzd A Katki,Mark Booth,Britton Trabert,Robert N Hoover

doi:10.3390/ijerph17041185

Abstract

Timing of breast development (or thelarche) and its endogenous and exogenous determinants may underlie global variation in breast cancer incidence. The study objectives were to characterize endogenous estrogen levels and bisphenol A (BPA) exposure using a migrant study of adolescent girls and test whether concentrations explained differences in thelarche by birthplace and growth environment. Estrogen metabolites (EM) and BPA-glucuronide (BPA-G) were quantified in urine spot samples using liquid chromatography tandem mass spectrometry (LC-MS/MS) from a cross-sectional study of Bangladeshi, first- and second-generation Bangladeshi migrants to the UK, and white British girls aged 5–16 years (n = 348). Thelarche status at the time of interview was self-reported and defined equivalent to Tanner Stage ≥2. We compared geometric means (and 95% confidence interval (CIs)) of EM and BPA-G using linear regression and assessed whether EM and BPA-G explained any of the association between exposure to the UK and the age at thelarche using hazard ratios and 95% confidence intervals. Average EM decreased with exposure to the UK, whereas BPA-G increased and was significantly higher among white British (0.007 ng/mL, 95% CI: 0.0024–0.0217) and second-generation British-Bangladeshi girls (0.009 ng/mL, 95% CI: 0.0040–0.0187) compared to Bangladeshi girls (0.002 ng/mL, 95% CI: 0.0018–0.0034). Two of four EM ratios (16-pathway/parent and parent/all pathways) were significantly associated with thelarche. The relationship between exposure to the UK and thelarche did not change appreciably after adding EM and BPA-G to the models. While BPA-G is often considered a ubiquitous exposure, our findings suggest it can vary based on birthplace and growth environment, with increasing levels for girls who were born in or moved to the UK. Our study did not provide statistically significant evidence that BPA-G or EM concentrations explained earlier thelarche among girls who were born or raised in the UK.

Highlights

Breast cancer incidence varies widely by country, with some of the highest rates in Western Europe and lowest in Asia [1]
The time period between thelarche and menarche may be relevant for breast cancer risk because the length of time between these two milestones may indicate a sensitive time period when individuals are more susceptible to exposures to exogenous estrogenic chemicals
While we found some differences in thelarche by Estrogen metabolites (EM) pathway or route of metabolism, our study did not provide evidence to suggest that variation in EM or bisphenol A (BPA)-G explained differences in thelarche between groups reported in our prior publication [14]

Summary

Introduction

Breast cancer incidence varies widely by country, with some of the highest rates in Western Europe and lowest in Asia [1]. The age-standardized breast cancer incidence rates in 2018 were nearly six times higher in the United Kingdom (UK) (93.6 per 1,000,000) than in Bangladesh Several epidemiological studies have focused on the role of endogenous hormone levels and breast cancer risk, and have used age at menarche as a proxy for the first dose of cumulative lifetime estrogen levels. The time period between thelarche and menarche may be relevant for breast cancer risk because the length of time between these two milestones may indicate a sensitive time period when individuals are more susceptible to exposures to exogenous estrogenic chemicals. Early puberty, either as a proxy of endogenous exposure dose or a longer sensitive window to exogenous factors, may have direct or indirect effects on breast cancer risk later in life

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