Exposure to perfluoroalkyl substances and risk of hepatocellular carcinoma in a multiethnic cohort

Goodrich, Jesse A.; Walker, Douglas I.; Lin, Xiangping; Wang, Hongxu; Lim, Tiffany; McConnell, Rob; Conti, David V.; Chatzi, Lida; Setiawan, Veronica Wendy

doi:10.1016/j.jhepr.2022.100550

Cited by 50 publications

(42 citation statements)

References 62 publications

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“…The specific LC-HRMS protocol used to measure plasmas PFAS for this study has been described previously. 59 Briefly, plasma samples were prepared by combining

of plasma with

of an internal standard. The internal standard contained thirty

-labeled PFAS to obtain a final

concentration.…”

Section: Methodsmentioning

confidence: 99%

“… 61 , 62 Measuring untargeted metabolomics was performed using established methods, 63 as described previously. 59 Briefly, LC-HRMS was performed with RP and hydrophilic interaction LC (HILIC) by employing a dual polarity/dual column approach. Analyses were performed with a Thermo Fisher Vanquish Duo LC system with dual pumps and columns with independent flow paths connected to a Thermo Fisher Q Exactive HF-X Orbitrap MS system.…”

Section: Methodsmentioning

confidence: 99%

“…Before analysis, samples for RP were prepared using the methods described above in the section “Plasma PFAS”. 59 Samples for HILIC were prepared using the methods described above, with minor alterations in the volumes as described previously. Specifically, for HILIC mode,

of acetonitrile was added to

of plasma before processing was continued as described above.…”

Section: Methodsmentioning

confidence: 99%

“…As described previously, samples were analyzed with both positive and negative ionization by optimizing mobile phases. 59 Separation for RP was performed using

(TARGA

; Higgins Analytical), whereas separation for HILIC was performed using a SeQuant ZIC-HILIC column (

, 200A

; MilliporeSigma) for positive mode, and an Amide ethylene bridged hybrid (BEH) HILIC column (

, 130A

; Waters) in negative mode. Measurement of mass spectral data was performed for a mass-to-charge ratio (m/z) scan range of 85 to 1,275, and the resolution was 120,000 full width at half maximum (FWHM).…”

Section: Methodsmentioning

confidence: 99%

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Metabolic Signatures of Youth Exposure to Mixtures of Per- and Polyfluoroalkyl Substances: A Multi-Cohort Study

Goodrich

Walker

et al. 2023

Environ Health Perspect

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Background: Exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous and has been associated with an increased risk of several cardiometabolic diseases. However, the metabolic pathways linking PFAS exposure and human disease are unclear. Objective: We examined associations of PFAS mixtures with alterations in metabolic pathways in independent cohorts of adolescents and young adults. Methods: Three hundred twelve overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) and 137 young adults from the Southern California Children’s Health Study (CHS) were included in the analysis. Plasma PFAS and the metabolome were determined using liquid-chromatography/high-resolution mass spectrometry. A metabolome-wide association study was performed on log-transformed metabolites using Bayesian regression with a g-prior specification and g-computation for modeling exposure mixtures to estimate the impact of exposure to a mixture of six ubiquitous PFAS (PFOS, PFHxS, PFHpS, PFOA, PFNA, and PFDA). Pathway enrichment analysis was performed using Mummichog and Gene Set Enrichment Analysis. Significance across cohorts was determined using weighted -tests. Results: In the SOLAR and CHS cohorts, PFAS exposure was associated with alterations in tyrosine metabolism (meta-analysis ) and de novo fatty acid biosynthesis ( ), among others. For example, when increasing all PFAS in the mixture from low ( th percentile) to high ( th percentile), thyroxine (T4), a thyroid hormone related to tyrosine metabolism, increased by 0.72 standard deviations (SDs; equivalent to a standardized mean difference) in the SOLAR cohort (95% Bayesian credible interval (BCI): 0.00, 1.20) and 1.60 SD in the CHS cohort (95% BCI: 0.39, 2.80). Similarly, when going from low to high PFAS exposure, arachidonic acid increased by 0.81 SD in the SOLAR cohort (95% BCI: 0.37, 1.30) and 0.67 SD in the CHS cohort (95% BCI: 0.00, 1.50). In general, no individual PFAS appeared to drive the observed associations. Discussion: Exposure to PFAS is associated with alterations in amino acid metabolism and lipid metabolism in adolescents and young adults. https://doi.org/10.1289/EHP11372

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“…The specific LC-HRMS protocol used to measure plasmas PFAS for this study has been described previously. 59 Briefly, plasma samples were prepared by combining

of plasma with

of an internal standard. The internal standard contained thirty

-labeled PFAS to obtain a final

concentration.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

of acetonitrile was added to

of plasma before processing was continued as described above.…”

Section: Methodsmentioning

confidence: 99%

“…As described previously, samples were analyzed with both positive and negative ionization by optimizing mobile phases. 59 Separation for RP was performed using

(TARGA

; Higgins Analytical), whereas separation for HILIC was performed using a SeQuant ZIC-HILIC column (

, 200A

; MilliporeSigma) for positive mode, and an Amide ethylene bridged hybrid (BEH) HILIC column (

, 130A

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Metabolic Signatures of Youth Exposure to Mixtures of Per- and Polyfluoroalkyl Substances: A Multi-Cohort Study

Goodrich

Walker

et al. 2023

Environ Health Perspect

Self Cite

View full text Add to dashboard Cite

show abstract

“… 9 Review and meta-analysis of human population and experimental studies have demonstrated that PFAS are associated with hepatotoxicity and worse liver functions, and have also suggested the possibility of a higher risk of liver cancer. 10 , 11 However, although growing evidence implicates higher PFAS in abnormal liver biomarkers, for example, alanine aminotransferase (ALT), gamma-glutamyl transaminase (GGT), and bilirubin, [11] , [12] , [13] , [14] the specific association with FLD, especially AFLD, and with advanced liver disease requires additional exploration.…”

Section: Introductionmentioning

confidence: 99%