Exposure to phthalate-containing prescription drugs and the risk of colorectal adenocarcinoma: A Danish nationwide case-control study

Zandra Nymand Ennis*, Anton Pottegård, Thomas Patrick Ahern, Jesper Hallas, Per Damkier

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Purpose: Some drug products contain phthalates as excipients, and in vitro studies have demonstrated that phthalates interfere with cellular mechanisms involved in colorectal cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and risk of colorectal adenocarcinomas. Methods: We used the Danish Cancer Registry to identify all patients with incident colorectal adenocarcinoma from 2008 to 2015 (n = 25 814). Each cancer case was matched to ten population controls. Linking information from Danish registers, we quantified cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP) and dibutyl phthalate (DBP) as well as enteric phthalate polymers from orally administered drugs. The association between cumulative phthalate exposure and colorectal cancer was estimated using conditional logistic regression. Results: Cumulative exposure to ortho-phthalates exceeding 500 mg was associated with lower odds of colorectal cancer diagnosis (OR adj  = 0.89; 95% CI, 0.81-0.96). Similar associations were observed for all DEP exposure exceeding 500 mg. Subgroup analysis excluding NSAID users, demonstrated that ortho-phthalate exposure was positively associated with colorectal cancer (OR adj  = 1.26; 95% CI, 1.05-1.51). Conclusion: We found an apparent overall protective effect of cumulative phthalate exposure from drug excipients for colorectal adenocarcinoma. Omitting NSAID users reversed the signal and suggested a slightly increased risk associated with high cumulative ortho-phthalate exposure.

OriginalsprogEngelsk
TidsskriftPharmacoepidemiology and Drug Safety
Vol/bind28
Udgave nummer4
Sider (fra-til)528-535
ISSN1053-8569
DOI
StatusUdgivet - 2019

Fingeraftryk

Case-Control Studies
Colorectal Neoplasms
Excipients
Pharmaceutical Preparations
phthalic acid
Dibutyl Phthalate
Population Control
Registries
Neoplasms
Logistic Models

Citer dette

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title = "Exposure to phthalate-containing prescription drugs and the risk of colorectal adenocarcinoma: A Danish nationwide case-control study",
abstract = "Purpose: Some drug products contain phthalates as excipients, and in vitro studies have demonstrated that phthalates interfere with cellular mechanisms involved in colorectal cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and risk of colorectal adenocarcinomas. Methods: We used the Danish Cancer Registry to identify all patients with incident colorectal adenocarcinoma from 2008 to 2015 (n = 25 814). Each cancer case was matched to ten population controls. Linking information from Danish registers, we quantified cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP) and dibutyl phthalate (DBP) as well as enteric phthalate polymers from orally administered drugs. The association between cumulative phthalate exposure and colorectal cancer was estimated using conditional logistic regression. Results: Cumulative exposure to ortho-phthalates exceeding 500 mg was associated with lower odds of colorectal cancer diagnosis (OR adj  = 0.89; 95{\%} CI, 0.81-0.96). Similar associations were observed for all DEP exposure exceeding 500 mg. Subgroup analysis excluding NSAID users, demonstrated that ortho-phthalate exposure was positively associated with colorectal cancer (OR adj  = 1.26; 95{\%} CI, 1.05-1.51). Conclusion: We found an apparent overall protective effect of cumulative phthalate exposure from drug excipients for colorectal adenocarcinoma. Omitting NSAID users reversed the signal and suggested a slightly increased risk associated with high cumulative ortho-phthalate exposure.",
keywords = "colorectal neoplasms, Denmark, dibutyl phthalate, diethyl phthalate, excipients, pharmacoepidemiology",
author = "Ennis, {Zandra Nymand} and Anton Potteg{\aa}rd and Ahern, {Thomas Patrick} and Jesper Hallas and Per Damkier",
year = "2019",
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language = "English",
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pages = "528--535",
journal = "Pharmacoepidemiology and Drug Safety",
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Exposure to phthalate-containing prescription drugs and the risk of colorectal adenocarcinoma : A Danish nationwide case-control study. / Ennis, Zandra Nymand; Pottegård, Anton; Ahern, Thomas Patrick; Hallas, Jesper; Damkier, Per.

I: Pharmacoepidemiology and Drug Safety, Bind 28, Nr. 4, 2019, s. 528-535.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Exposure to phthalate-containing prescription drugs and the risk of colorectal adenocarcinoma

T2 - A Danish nationwide case-control study

AU - Ennis, Zandra Nymand

AU - Pottegård, Anton

AU - Ahern, Thomas Patrick

AU - Hallas, Jesper

AU - Damkier, Per

PY - 2019

Y1 - 2019

N2 - Purpose: Some drug products contain phthalates as excipients, and in vitro studies have demonstrated that phthalates interfere with cellular mechanisms involved in colorectal cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and risk of colorectal adenocarcinomas. Methods: We used the Danish Cancer Registry to identify all patients with incident colorectal adenocarcinoma from 2008 to 2015 (n = 25 814). Each cancer case was matched to ten population controls. Linking information from Danish registers, we quantified cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP) and dibutyl phthalate (DBP) as well as enteric phthalate polymers from orally administered drugs. The association between cumulative phthalate exposure and colorectal cancer was estimated using conditional logistic regression. Results: Cumulative exposure to ortho-phthalates exceeding 500 mg was associated with lower odds of colorectal cancer diagnosis (OR adj  = 0.89; 95% CI, 0.81-0.96). Similar associations were observed for all DEP exposure exceeding 500 mg. Subgroup analysis excluding NSAID users, demonstrated that ortho-phthalate exposure was positively associated with colorectal cancer (OR adj  = 1.26; 95% CI, 1.05-1.51). Conclusion: We found an apparent overall protective effect of cumulative phthalate exposure from drug excipients for colorectal adenocarcinoma. Omitting NSAID users reversed the signal and suggested a slightly increased risk associated with high cumulative ortho-phthalate exposure.

AB - Purpose: Some drug products contain phthalates as excipients, and in vitro studies have demonstrated that phthalates interfere with cellular mechanisms involved in colorectal cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and risk of colorectal adenocarcinomas. Methods: We used the Danish Cancer Registry to identify all patients with incident colorectal adenocarcinoma from 2008 to 2015 (n = 25 814). Each cancer case was matched to ten population controls. Linking information from Danish registers, we quantified cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP) and dibutyl phthalate (DBP) as well as enteric phthalate polymers from orally administered drugs. The association between cumulative phthalate exposure and colorectal cancer was estimated using conditional logistic regression. Results: Cumulative exposure to ortho-phthalates exceeding 500 mg was associated with lower odds of colorectal cancer diagnosis (OR adj  = 0.89; 95% CI, 0.81-0.96). Similar associations were observed for all DEP exposure exceeding 500 mg. Subgroup analysis excluding NSAID users, demonstrated that ortho-phthalate exposure was positively associated with colorectal cancer (OR adj  = 1.26; 95% CI, 1.05-1.51). Conclusion: We found an apparent overall protective effect of cumulative phthalate exposure from drug excipients for colorectal adenocarcinoma. Omitting NSAID users reversed the signal and suggested a slightly increased risk associated with high cumulative ortho-phthalate exposure.

KW - colorectal neoplasms

KW - Denmark

KW - dibutyl phthalate

KW - diethyl phthalate

KW - excipients

KW - pharmacoepidemiology

U2 - 10.1002/pds.4759

DO - 10.1002/pds.4759

M3 - Journal article

C2 - 30793813

AN - SCOPUS:85061961526

VL - 28

SP - 528

EP - 535

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

SN - 1053-8569

IS - 4

ER -