Papers of the Month
By Janelle Weaver
Breast cancer is linked to ambient radioactive particles
Airborne radioactive particles may contribute to the development of estrogen receptor–negative breast cancer, according to NIEHS researchers and their collaborators.
Outdoor air pollution has been classified as a human carcinogen based on evidence for lung cancer. The evidence for breast cancer risk is accumulating, although the specific constituents driving the association are not well explored. Particulate matter can be a vector for radioactive isotopes, most of which arise from naturally occurring radon gas, which has been linked to a higher risk of both breast and lung cancer.
To examine this issue, the researchers enrolled 50,884 women living in the U.S. between 2003 and 2009 in the Sister Study cohort. All participants had a sister diagnosed with breast cancer but no history of breast cancer themselves. The researchers tracked cases of breast cancer until 2019. With an average of 10 years of follow-up, 3,894 women were diagnosed with breast cancer.
Higher estimated residential exposure to ambient radioactive particulate matter was associated with an elevated risk of estrogen receptor–negative breast cancer, which has fewer treatment options. However, the data did not demonstrate a dose–response relationship, and according to the authors, more research is needed to confirm the findings.
Citation: White AJ, Gregoire AM, Fisher JA, Medgyesi DN, Li L, Koutrakis P, Sandler DP, Jones RR. 2022. Exposure to particle radioactivity and breast cancer risk in the Sister Study: A U.S.-wide prospective cohort. Environ Health Perspect 130(4):47701.
Exploring the link between phthalates and fetal health
Prenatal exposure to phthalates is modestly associated with reduced fetal growth, especially among certain subgroups, according to NIEHS researchers and their collaborators.
Phthalates are synthetic chemicals commonly used in personal care and hygiene products, as well as in food packaging, residential materials, and medical devices. Prenatal phthalate exposure has been linked to adverse maternal and fetal health outcomes, including pregnancy loss and preterm delivery. However, epidemiological evidence pointing to reductions in fetal growth has been mixed, likely due to methodological drawbacks such as examining weight at birth alone as a proxy for fetal growth in utero.
To overcome these shortcomings, the researchers measured exposure to multiple phthalates in urine samples collected from 604 pregnant women during early and late pregnancy. They found that a one-quartile increase in exposure to the overall phthalate mixture was modestly associated with reduced birth weight, as well as a decrease in birth length, in males but not in females.
Greater prenatal exposure to phthalates was associated with reduced fetal growth among participants with adequate omega-3 intake during pregnancy but not in those with inadequate omega-3 intake. This was surprising, given that omega-3 fatty acids, which came primarily from fish oil supplementation in this study, are anti-inflammatory. According to the authors, further research is needed to identify and understand the drivers of this relationship.
Citation: Stevens DR, Bommarito PA, Keil AP, McElrath TF, Trasande L, Barrett ES, Bush NR, Nguyen RHN, Sathyanarayana S, Swan S, Ferguson KK. 2022. Urinary phthalate metabolite mixtures in pregnancy and fetal growth: Findings from the infant development and the environment study. Environ Int 163:107235.
Pregnancy depends on crosstalk among uterine microenvironments
Unique microenvironments in the mouse uterus coordinate with each other to regulate pregnancy, according to NIEHS researchers and their collaborators.
Uterine dysfunctions lead to fertility disorders and pregnancy complications, which are significant health care issues in the United States. Normal uterine function during pregnancy requires communication between fetal and maternal tissue as well as among various compartments of the uterus. Understanding the communication between these compartments and the microenvironments established during pregnancy is crucial to determine mechanisms that lead to pregnancy complications.
Toward this goal, the researchers used a mouse model to identify uterine microenvironments during early pregnancy. The study provided a 2D atlas of the uterine transcriptome — the collection of all the gene readouts present in cells. Analysis of these gene signatures revealed 11 different microenvironments, each of which has distinct biological functions and hormonal responses. In addition, these microenvironments coordinate with each other intensively as a whole system to regulate pregnancy.
According to the authors, the high-resolution transcriptome profiles may facilitate future investigations on the molecular mechanisms underlying the progression of normal pregnancy. Further refinement of the atlas of the pregnant uterus could yield additional information that ultimately improves pregnancy health.
Citation: Li R, Wang TY, Xu X, Emery O, Yi M, Wu SP, DeMayo FJ. Spatial transcriptomic profiles of mouse uterine microenvironments at pregnancy day 7.5. Biol Reprod; doi:10.1093/biolre/ioac061 [Online 31 Mar 2022]. (Story)
Researchers identify risk factors for disease flares after COVID-19 vaccination
Flares are infrequently reported after COVID-19 vaccination in patients with systemic rheumatic disease (SRD), according to NIEHS researchers and their collaborators.
SRD is an inflammatory disorder that involves multiple organs and often requires immunosuppressant therapy. SRD flares have been uncommonly reported after immunization with vaccines against influenza and herpes zoster, also known as shingles. The researchers set out to examine the frequency of, and risk factors for, flares after COVID-19 vaccination in patients with SRD.
Among the 5,691 adults in the international study, which was conducted from April 2 to August 16, 2021, SRD flares requiring changes in SRD treatments after COVID-19 vaccines occurred in approximately 5% of online survey respondents. Compared to rheumatoid arthritis, the risk was higher for systemic lupus erythematosus, psoriatic arthritis, and polymyalgia rheumatica, and lower for inflammatory myopathies. In addition, the odds of flare were elevated among female patients, patients who received the Oxford-AstraZeneca vaccine rather than the Pfizer-BioNTech vaccine, or patients who had a previous reaction to a non−COVID-19 vaccine.
According to the authors, these results should be interpreted cautiously, and they called for future controlled, prospective clinical studies to determine rates and predictors of flares after COVID-19 vaccination in patients with SRD.
Citation: Rider LG, Parks CG, Wilkerson J, Schiffenbauer AI, Kwok RK, Noroozi Farhadi P, Nazir S, Ritter R, Sirotich E, Kennedy K, Larche MJ, Levine M, Sattui SE, Liew JW, Harrison CO, Moni TT, Miller AK, Putman M, Hausmann J, Simard JF, Sparks JA, Miller FW. Baseline factors associated with self-reported disease flares following COVID-19 vaccination among adults with systemic rheumatic disease: Results from the COVID-19 global rheumatology alliance vaccine survey. Rheumatology; doi:10.1093/rheumatology/keac249 [Online 23 April 2022].