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

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.

Bisphenols and Risk of Breast Cancer: A Narrative Review of the Impact of Diet and Bioactive Food Components

“…In a study with Bangladeshi, firstand second-generation Bangladeshi migrants to the UK, and white British girls, the average urinary BPAG increases and is significantly higher among white British (0.007 ng/mL) and second-generation British-Bangladeshi girls (0.009 ng/mL) compared to Bangladeshi girls (0.002 ng/mL). These findings point to birthplace and growth environment as variables affecting exposure to bisphenols (84). A study within the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort (n = 120 girls, age 8-13 years), shows that BPA in the second trimester associates in offspring girls with higher peripubertal testosterone and higher odds of having a Tanner Stage >1 for breast development (OR/IQR: 2.2; 95%CI: 1.0, 4.5).…”

Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing

“…We sampled first-and second-generation British-Bangladeshi women representing participants in our numerous previous studies from which we have reported rich quantitative and qualitative data on diet, lifestyles, migration, and demographic histories [10,12,13,28,29,109]. The samples analyzed here were from women aged 21-35 years, recruited in London through community contacts using snowballing techniques.…”

“…Given the inherent problems of reproductive tissue inaccessibility in healthy human subjects, we set out to identify genes associated with altered DNA methylation in buccal tissue of Bangladeshi migrant women who had grown up in Bangladesh or the UK and to compare and integrate these findings with changes in gene expression in the reproductive tissues of a suitable mouse model. We first established such a mouse model based on findings that the "Bangladeshi childhood" reproductive phenotype, including delayed menarche and reduced ovarian reserve, was associated with increased inflammatory burden from infectious and parasitic diseases prior to puberty [10,12,13] and did not appear to be due to differential exposure to endocrine disruptors [28,29].…”