Internal chemical exposure study among Mexican immigrants

Institution: University of California, San Francisco
Investigator(s): Laura Fejerman, Ph.D. -
Award Cycle: 2013 (Cycle 19) Grant #: 19IB-0147 Award: $124,414
Award Type: IDEA
Research Priorities
Etiology and Prevention>Etiology: the role of environment and lifestyle

Initial Award Abstract (2013)

Non-technical overview of the research topic and relevance to breast cancer: Breast cancer risk increases with number of generations in the U.S. and with younger age at migration among U.S. Latinas. These observations strongly suggest that the changes in the environment and lifestyle associated with longer residence in the U.S., increase Latina women’s exposure to harmful factors and as a result increase their breast cancer risk. Previous studies have attempted to identify the factors that could explain the differences in breast cancer risk among Latina immigrants using measures of exposure obtained through questionnaires. However most of these studies are limited to epidemiological associations without further insights into underlying mechanisms. It is known that people with similar reported exposures are not equally susceptible to disease, probably due to variation in the way substances produced within or outside our bodies are broken down and handled by our organisms. There is a need for new studies that objectively assess internal levels of exposure among U.S. immigrants. Our study will assess how the migratory experience influences the levels of potentially harmful substances present in the blood of Mexican Americans women increasing their risk of developing breast cancer.

The question(s) or central hypotheses of the research: We hypothesize that women who have been exposed to the U.S. environment and lifestyle for longer and from a younger age, will have higher levels of harmful substances in their blood. We also hypothesize that particular types of harmful compounds will measure at different levels depending on duration of residence in the U.S. and age at migration as well as when comparing breast cancer cases and controls.

The general methodology: We will measure multiple chemical exposures that are detectable within the body of any given individual without targeting any one in particular. Similar to the shift from candidate gene studies to genome-wide association studies (GWAS) in investigations of the genetic etiology of diseases, our project proposes a shift from breast cancer candidate exposure analysis to an exposure-wide analysis. We plan to use mass- spectrometry (a substance separation procedure) and cell-based assays to measure two types of harmful substances: reactive electrophiles (substances attracted to electrons that damage DNA and proteins) and hormone receptor disruptors (chemicals that mimic the effect of estrogen or androgen on cell receptors). We will evaluate the levels of these two compounds among 90 Mexican American women who participated in the San Francisco Bay Area Breast Cancer Study (SFBCS), a population-based case-control study of women aged 35 to 79 years. We will compare levels of 30 women born in the U.S., 30 born in Mexico who moved to the U.S. before puberty (as marked by first menstrual cycle), and 30 who moved to the U.S. as adults (at age 21 years or older). Each migration group will include equal numbers of pre- and post-menopausal women. Through linkage with the California Cancer Registry, we expect to identify approximately 30 women who developed breast cancer since they participated in the study. We will contrast the reactive electrophile levels and hormone receptor disruptor activity of these cases to those of women who have not yet developed the disease.

Innovative elements of the project: The innovation in this proposal comes from the idea of combining information on migration history with untargeted measures of internal exposure to harmful substances among Mexican Americans. By avoiding a priori assumptions about what specific chemicals are likely to affect breast cancer risk, we expect to open new avenues of research and discover new biological markers of risk (or biomarkers) as well as new modifiable risk factors that could be targeted through prevention programs to reduce breast cancer incidence among higher generation Latinas.

Final Report (2016)

Overview: When Latin American women migrate to the US, their risk of developing breast cancer increases. This suggests that there are changes in their environmental exposures or in their lifestyle choices that directly affect their organisms and predispose them to breast cancer development. Even though associations have been described between different breast cancer risk factors and place of birth among US Latinas, there is still a proportion of the change in breast cancer risk that has not been accounted for. We proposed to use semi-targeted and untargeted approaches to discover new possible breast cancer risk factors that could explain the difference in risk between foreign-born and US-born Latinas.

Description of completed aims: We successfully estimated estrogen receptor (ER) activity in 90 Mexican American women and glucocorticoid receptor (GR) activity in 63 women. We tested the association between levels of activity for the different receptors and nativity, failing to observe any statistically significant associations. The ER receptor activity, as well as an analysis measuring the level of small reactive molecules in plasma, showed associations with proportion of Indigenous American ancestry as well as with years in the US since the time of migration. A multivariate analysis showed a suggestive association between GR activity levels and case/control status.

Barriers: The generation of the small reactive molecules data was delayed due to changes in the mass-spectrometry technology. However the analysis was conducted successfully during the one-year no-cost extension of the grant.

Major accomplishments: successful characterization of ER levels in all samples and of GR levels in 2/3 of the samples; characterization of a 46-Adduct panel (small reactive molecules) in all samples; characterization of all small-molecules (metabolites) using mass spectrometry in the 90 samples adding more exposomics data to our study. Results were presented at multiple scientific meetings, including one oral presentation. We obtained preliminary data for a successful grant application to continue our work on internal chemical exposures and breast cancer risk (from the California Breast Cancer Research Program), and for two additional grant applications.

Future plans: We will identify specific chemicals affecting estrogenic activity in a multiethnic cohort through an ongoing study. Conditional on obtaining additional founding, we will confirm and further explore the relationship between Indigenous American ancestry and internal chemical exposures in a larger sample of Latina women, incorporating behavioral traits and neighborhood context.

Association of lifestyle and demographic factors with estrogenic and glucocorticogenic activity in Mexican American women doi: 10.1093/carcin/bgw074
Index Medicus: Carcinogenesis
Authors: L Fejerman, SS Sanchez, R Thomas, P Tachachartvanich, J Riby, SL Gomez, EM John, MT Smith
Yr: 2016 Vol: 37 Nbr: 9 Abs: Pg:904-11