Exposome epidemiology for suspect environmental chemical exposures during pregnancy linked to subsequent breast cancer diagnosis

Go, Young‐Mi; Weinberg, Jaclyn; Teeny, Sami; Cirillo, Piera M.; Krigbaum, Nickilou Y.; Singer, Grant; Ly, ViLinh; Cohn, Barbara A.; Jones, Dean P.

doi:10.1016/j.envint.2023.108112

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…Cases were defined as women with incident invasive or noninvasive breast cancer diagnosed at a median age at diagnosis of 54 years (interquartile range, 13 years) with available prenatal serum. Third (T3) trimester samples of 172 women who subsequently developed breast cancer were analyzed along with samples from 351 women from the cohort who did not develop breast cancer [ 17 ]. Of women with breast cancer, 34 had cancer diagnosis within 15 years of pregnancy.…”

Section: Methodsmentioning

confidence: 99%

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Third Trimester Serum Amino Acid Metabolism is Associated with Maternal Breast Cancer Diagnosed within 15 years of Pregnancy

Teeny,

Jarrell,

Krigbaum

et al. 2023

Preprint

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A prospective metabolome-wide association study revealed widespread amino acid limitation in late pregnancy is associated with early onset breast cancer. Archival third trimester pregnancy serum samples from 172 women who subsequently were diagnosed with breast cancer within 38 years after pregnancy were compared to 351 women without breast cancer. No individual metabolite differed after false discovery rate adjustment, indicating that individual metabolites are unlikely to be useful for classification or prediction. Despite this, pathway enrichment analysis showed that amino acid pathways, including lysine, arginine, proline, aspartate, asparagine, alanine, tyrosine, tryptophan, histidine, branched-chain amino acid and urea cycle, were enriched among metabolites that differed at raw p < 0.05. Several of these pathways previously were linked to breast carcinogen exposures, including dichlorodiphenyltrichloroethane and perfluorinated alkyl substances. Network analyses showed that amino acids correlated with parity and the ratio of estriol to estrone and estradiol known risk factors for breast cancer in this cohort. Overall, amino acid associations were stronger for early onset breast cancer, defined here as occurring within the first 15 years following pregnancy. Although results must be interpreted cautiously, lower amino acid concentrations for histidine, threonine and proline, and stronger associations for tryptophan, histidine, and lysine pathways with breast cancer within 15 years, suggests that amino acid limitations during late pregnancy contribute to metabolic reprogramming that is causally related to early onset breast cancer. Environmental chemical effects on nutrient sensing could account for these effects through known oncogenic mechanisms linked to nutrient stress.

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Section: Methodsmentioning

confidence: 99%

“…Peak detection, noise removal, and alignment of retention times and features were performed using the adaptive processing for LC-MS data (apLCMS) v.6.6.8 R package [ 17 , 19 – 21 ]. Additional filtering of low-quality samples and features and batch correction were conducted with xMSanalyzer v.1.3.2 [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Third Trimester Serum Amino Acid Metabolism is Associated with Maternal Breast Cancer Diagnosed within 15 years of Pregnancy

Teeny,

Jarrell,

Krigbaum

et al. 2023

Preprint

Self Cite

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“…In addition, the same pollutants are thought to be responsible for a worldwide decline in sperm counts which, if the present rate of decline continues unabated, will ultimately have an impact on the long-term fecundity of our species ( Levine et al 2023 ). Not surprisingly, environmental toxicants also impact the female reproductive system ( Dutta et al 2022 , Go et al , 2023 ) and are thought to play a direct role in the causation of infertility across both sexes ( Canipari et al 2020 , Erenpreisa et al 2023 ).…”

Section: Environmental Pollutionmentioning

confidence: 99%

Population decline: where demography, social science, and biology intersect

Aitken

2024

Reproduction

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Since the early 1960’s the world has witnessed the spectacular collapse of human fertility. As a result of this phenomenon several countries are already seeing their population numbers fall and more will follow in the coming decades. The causes of this fertility decline involve a complex interplay of socioeconomic, environmental, and biological factors that have converged to constrain fertility in posterity’s wake. Since large numbers of offspring are no longer needed to compensate for high infant mortality in contemporary society, couples have opted to have small families in a quality-over-quantity investment in their progeny’s future. Simultaneously, increases in female education, the enhanced participation of women in the paid workforce, and a resultant delay in childbearing has placed limits on achievable family size. Progressive urbanization, the improved availability of contraceptives and the socioeconomic pressures experienced by young adults in ageing societies, are also contributing to fertility’s demise. These factors together with the individualism that pervades modern society and the increasing social acceptability of voluntary childlessness, have firmly established a low fertility ethos in most post-transition countries. Since none of these forces are about to relent, it looks as if extremely low fertility might be with us for some time to come. This may have long-term consequences. The lack of selection pressure on high fertility genotypes, the ability of ART to retain poor fertility genotypes within the population and sustained exposure to reproductive toxicants in modern industrialized environments, may all contrive to leave a permanent mark on the fecundity of our species.

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“…Therefore, they can aid in the early detection of cancer, even before the appearance of symptoms. Early identification is frequently associated with better treatment results and greater survival rates [5,[10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The VISTA/VSIG3/PSGL-1 axis: crosstalk between immune effector cells and cancer cells in invasive ductal breast carcinoma

Olbromski,

Mrozowska,

Piotrowska

et al. 2024

Cancer Immunol Immunother

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A checkpoint protein called the V-domain Ig suppressor of T cell activation (VISTA) is important for controlling immune responses. Immune cells that interact with VISTA have molecules, or receptors, known as VISTA receptors. Immune system activity can be modified by the interaction between VISTA and its receptors. Since targeting VISTA or its receptors may be beneficial in certain conditions, VISTA has been studied in relation to immunotherapy for cancer and autoimmune illnesses. The purpose of this study was to examine the expression levels and interactions between VISTA and its receptors, VSIG3 and PSGL-1, in breast cancer tissues. IHC analysis revealed higher levels of proteins within the VISTA/VSIG3/PSGL-1 axis in cancer tissues than in the reference samples (mastopathies). VISTA was found in breast cancer cells and intratumoral immune cells, with membranous and cytoplasmic staining patterns. VISTA was also linked with pathological grade and VSIG3 and PSGL-1 levels. Furthermore, we discovered that the knockdown of one axis member boosted the expression of the other partners. This highlights the significance of VISTA/VSIG3/PSGL-1 in tumor stroma and microenvironment remodeling. Our findings indicate the importance of the VISTA/VSIG3/PSGL-1 axis in the molecular biology of cancer cells and the immune microenvironment.

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Exposome epidemiology for suspect environmental chemical exposures during pregnancy linked to subsequent breast cancer diagnosis

Cited by 7 publications

References 38 publications

Third Trimester Serum Amino Acid Metabolism is Associated with Maternal Breast Cancer Diagnosed within 15 years of Pregnancy

Third Trimester Serum Amino Acid Metabolism is Associated with Maternal Breast Cancer Diagnosed within 15 years of Pregnancy

Population decline: where demography, social science, and biology intersect

The VISTA/VSIG3/PSGL-1 axis: crosstalk between immune effector cells and cancer cells in invasive ductal breast carcinoma

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