Medication-Associated Phthalate Exposure and Childhood Cancer Incidence

Thomas P. Ahern; Logan G. Spector; Per Damkier; Buket Öztürk Esen; Sinna P. Ulrichsen; Katrine Eriksen; Timothy L. Lash; Henrik Toft Sørensen; Deirdre P. Cronin-Fenton

doi:10.1093/jnci/djac045

Medication-Associated Phthalate Exposure and Childhood Cancer Incidence

Thomas P. Ahern^*, Logan G. Spector, Per Damkier, Buket Öztürk Esen, Sinna P. Ulrichsen, Katrine Eriksen, Timothy L. Lash, Henrik Toft Sørensen, Deirdre P. Cronin-Fenton

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

BACKGROUND: Human phthalate exposure is widespread through contact with myriad consumer products. Exposure is particularly high through medications formulated with phthalates. Phthalates disrupt normal endocrine signaling and are associated with reproductive outcomes and incidence of some cancers. We measured associations between gestational and childhood medication-associated phthalate exposures and the incidence of childhood cancers. METHODS: We identified all live births in Denmark between 1997 and 2017, including both children and birth mothers. Using drug ingredient data merged with the Danish National Prescription Registry, we measured phthalate exposure through filled prescriptions for mothers during pregnancy (gestational exposure) and for children from birth until age 19 years (childhood exposure). Incident childhood cancers were ascertained from the Danish Cancer Registry, and associations were estimated with Cox regression models. RESULTS: Among 1 278 685 children, there were 2027 childhood cancer cases diagnosed over 13.1 million person-years of follow-up. Childhood phthalate exposure was strongly associated with incidence of osteosarcoma (hazard ratio [HR] = 2.78, 95% confidence interval [CI] = 1.63 to 4.75). We also observed a positive association with incidence of lymphoma (HR = 2.07, 95% CI = 1.36 to 3.14), driven by associations with Hodgkin and non-Hodgkin lymphoma but not Burkitt lymphoma. Associations were apparent only for exposure to low-molecular phthalates, which have purportedly greater biological activity. CONCLUSIONS: Childhood phthalate exposure was associated with incidence of osteosarcoma and lymphoma before age 19 years. Lingering questions include which specific phthalate(s) are responsible for these associations, by what mechanisms they occur, and to what extent childhood cancer cases could be avoided by reducing or eliminating the phthalate content of medications and other consumer products.

Originalsprog	Engelsk
Tidsskrift	Journal of the National Cancer Institute
Vol/bind	114
Nummer	6
Sider (fra-til)	885-894
Antal sider	10
ISSN	0027-8874
DOI	https://doi.org/10.1093/jnci/djac045
Status	Udgivet - jun. 2022

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10.1093/jnci/djac045

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194627/pdf/djac045.pdf

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@article{9a76532a8aef4771a13a4f0d774f7a5f,

title = "Medication-Associated Phthalate Exposure and Childhood Cancer Incidence",

abstract = "BACKGROUND: Human phthalate exposure is widespread through contact with myriad consumer products. Exposure is particularly high through medications formulated with phthalates. Phthalates disrupt normal endocrine signaling and are associated with reproductive outcomes and incidence of some cancers. We measured associations between gestational and childhood medication-associated phthalate exposures and the incidence of childhood cancers. METHODS: We identified all live births in Denmark between 1997 and 2017, including both children and birth mothers. Using drug ingredient data merged with the Danish National Prescription Registry, we measured phthalate exposure through filled prescriptions for mothers during pregnancy (gestational exposure) and for children from birth until age 19 years (childhood exposure). Incident childhood cancers were ascertained from the Danish Cancer Registry, and associations were estimated with Cox regression models. RESULTS: Among 1 278 685 children, there were 2027 childhood cancer cases diagnosed over 13.1 million person-years of follow-up. Childhood phthalate exposure was strongly associated with incidence of osteosarcoma (hazard ratio [HR] = 2.78, 95% confidence interval [CI] = 1.63 to 4.75). We also observed a positive association with incidence of lymphoma (HR = 2.07, 95% CI = 1.36 to 3.14), driven by associations with Hodgkin and non-Hodgkin lymphoma but not Burkitt lymphoma. Associations were apparent only for exposure to low-molecular phthalates, which have purportedly greater biological activity. CONCLUSIONS: Childhood phthalate exposure was associated with incidence of osteosarcoma and lymphoma before age 19 years. Lingering questions include which specific phthalate(s) are responsible for these associations, by what mechanisms they occur, and to what extent childhood cancer cases could be avoided by reducing or eliminating the phthalate content of medications and other consumer products.",

keywords = "Adult, Child, Environmental Exposure/adverse effects, Female, Humans, Incidence, Osteosarcoma, Phthalic Acids/adverse effects, Pregnancy, Registries, Young Adult",

author = "Ahern, {Thomas P.} and Spector, {Logan G.} and Per Damkier and {{\"O}zt{\"u}rk Esen}, Buket and Ulrichsen, {Sinna P.} and Katrine Eriksen and Lash, {Timothy L.} and S{\o}rensen, {Henrik Toft} and Cronin-Fenton, {Deirdre P.}",

year = "2022",

month = jun,

doi = "10.1093/jnci/djac045",

language = "English",

volume = "114",

pages = "885--894",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Medication-Associated Phthalate Exposure and Childhood Cancer Incidence

AU - Ahern, Thomas P.

AU - Spector, Logan G.

AU - Damkier, Per

AU - Öztürk Esen, Buket

AU - Ulrichsen, Sinna P.

AU - Eriksen, Katrine

AU - Lash, Timothy L.

AU - Sørensen, Henrik Toft

AU - Cronin-Fenton, Deirdre P.

PY - 2022/6

Y1 - 2022/6

N2 - BACKGROUND: Human phthalate exposure is widespread through contact with myriad consumer products. Exposure is particularly high through medications formulated with phthalates. Phthalates disrupt normal endocrine signaling and are associated with reproductive outcomes and incidence of some cancers. We measured associations between gestational and childhood medication-associated phthalate exposures and the incidence of childhood cancers. METHODS: We identified all live births in Denmark between 1997 and 2017, including both children and birth mothers. Using drug ingredient data merged with the Danish National Prescription Registry, we measured phthalate exposure through filled prescriptions for mothers during pregnancy (gestational exposure) and for children from birth until age 19 years (childhood exposure). Incident childhood cancers were ascertained from the Danish Cancer Registry, and associations were estimated with Cox regression models. RESULTS: Among 1 278 685 children, there were 2027 childhood cancer cases diagnosed over 13.1 million person-years of follow-up. Childhood phthalate exposure was strongly associated with incidence of osteosarcoma (hazard ratio [HR] = 2.78, 95% confidence interval [CI] = 1.63 to 4.75). We also observed a positive association with incidence of lymphoma (HR = 2.07, 95% CI = 1.36 to 3.14), driven by associations with Hodgkin and non-Hodgkin lymphoma but not Burkitt lymphoma. Associations were apparent only for exposure to low-molecular phthalates, which have purportedly greater biological activity. CONCLUSIONS: Childhood phthalate exposure was associated with incidence of osteosarcoma and lymphoma before age 19 years. Lingering questions include which specific phthalate(s) are responsible for these associations, by what mechanisms they occur, and to what extent childhood cancer cases could be avoided by reducing or eliminating the phthalate content of medications and other consumer products.

AB - BACKGROUND: Human phthalate exposure is widespread through contact with myriad consumer products. Exposure is particularly high through medications formulated with phthalates. Phthalates disrupt normal endocrine signaling and are associated with reproductive outcomes and incidence of some cancers. We measured associations between gestational and childhood medication-associated phthalate exposures and the incidence of childhood cancers. METHODS: We identified all live births in Denmark between 1997 and 2017, including both children and birth mothers. Using drug ingredient data merged with the Danish National Prescription Registry, we measured phthalate exposure through filled prescriptions for mothers during pregnancy (gestational exposure) and for children from birth until age 19 years (childhood exposure). Incident childhood cancers were ascertained from the Danish Cancer Registry, and associations were estimated with Cox regression models. RESULTS: Among 1 278 685 children, there were 2027 childhood cancer cases diagnosed over 13.1 million person-years of follow-up. Childhood phthalate exposure was strongly associated with incidence of osteosarcoma (hazard ratio [HR] = 2.78, 95% confidence interval [CI] = 1.63 to 4.75). We also observed a positive association with incidence of lymphoma (HR = 2.07, 95% CI = 1.36 to 3.14), driven by associations with Hodgkin and non-Hodgkin lymphoma but not Burkitt lymphoma. Associations were apparent only for exposure to low-molecular phthalates, which have purportedly greater biological activity. CONCLUSIONS: Childhood phthalate exposure was associated with incidence of osteosarcoma and lymphoma before age 19 years. Lingering questions include which specific phthalate(s) are responsible for these associations, by what mechanisms they occur, and to what extent childhood cancer cases could be avoided by reducing or eliminating the phthalate content of medications and other consumer products.

KW - Adult

KW - Child

KW - Environmental Exposure/adverse effects

KW - Female

KW - Humans

KW - Incidence

KW - Osteosarcoma

KW - Phthalic Acids/adverse effects

KW - Pregnancy

KW - Registries

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=85131902840&partnerID=8YFLogxK

U2 - 10.1093/jnci/djac045

DO - 10.1093/jnci/djac045

M3 - Journal article

C2 - 35179607

AN - SCOPUS:85131902840

SN - 0027-8874

VL - 114

SP - 885

EP - 894

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 6

ER -

Medication-Associated Phthalate Exposure and Childhood Cancer Incidence

Abstract

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