TY - JOUR
T1 - Use of phthalate-containing prescription drugs and the risk of gastric cancer
T2 - a Danish nationwide case-control study
AU - Nymand Ennis, Zandra
AU - Arnspang Pedersen, Sidsel
AU - Rix Hansen, Morten
AU - Pottegård, Anton
AU - Patrick Ahern, Thomas
AU - Hallas, Jesper
AU - Damkier, Per
PY - 2019/6/3
Y1 - 2019/6/3
N2 - Background: Phthalates are used as excipients in some drug products, and up to a 50-fold increased urinary excretion of phthalate metabolites compared to non-users has been demonstrated in users of such products. In vitro studies have demonstrated that phthalates stimulate mechanisms involved in gastric cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and the risk of gastric adenocarcinomas. Methods: Using the Danish Cancer Registry, we identified all patients with incident gastric adenocarcinoma from 2008 to 2015 (n = 1525). Cancer cases were matched to 10 controls. Linking information retrieved from nationwide Danish registries, we determined individual cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP), dibutyl phthalate (DBP) and enteric phthalate polymers from prescription drugs. The association between cumulative phthalate exposure and gastric adenocarcinoma was estimated using conditional logistic regression, adjusting for socioeconomical status and drugs or comorbidities known or suspected to modify the risk of gastric adenocarcinoma. Results: No association was seen for the risk of gastric adenocarcinomas among individuals with high cumulative exposure to ortho-phthalates (exceeding 500 mg) (ORadj 1.22, 95% CI: 0.84–1.77). Likewise, no associations were observed individually for DEP (ORadj 1.06 95% CI: 0.63–1.76) or DBP (ORadj 1.32 95% CI: 0.78–2.23). Cumulative exposure to enteric phthalate polymers exceeding 10,000 mg, did not reveal an association with gastric adenocarcinoma (ORadj 0.79, 95% CI: 0.54–1.16) and no association was seen for individual compounds. Additionally, no dose-response pattern was observed across exposure strata (p =.39, test for trend). Conclusion: We did not find an increased risk of gastric adenocarcinoma among Danish users of phthalate-containing drug products. Our study is limited by a low number of cases exposed to high cumulative doses of phthalates.
AB - Background: Phthalates are used as excipients in some drug products, and up to a 50-fold increased urinary excretion of phthalate metabolites compared to non-users has been demonstrated in users of such products. In vitro studies have demonstrated that phthalates stimulate mechanisms involved in gastric cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and the risk of gastric adenocarcinomas. Methods: Using the Danish Cancer Registry, we identified all patients with incident gastric adenocarcinoma from 2008 to 2015 (n = 1525). Cancer cases were matched to 10 controls. Linking information retrieved from nationwide Danish registries, we determined individual cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP), dibutyl phthalate (DBP) and enteric phthalate polymers from prescription drugs. The association between cumulative phthalate exposure and gastric adenocarcinoma was estimated using conditional logistic regression, adjusting for socioeconomical status and drugs or comorbidities known or suspected to modify the risk of gastric adenocarcinoma. Results: No association was seen for the risk of gastric adenocarcinomas among individuals with high cumulative exposure to ortho-phthalates (exceeding 500 mg) (ORadj 1.22, 95% CI: 0.84–1.77). Likewise, no associations were observed individually for DEP (ORadj 1.06 95% CI: 0.63–1.76) or DBP (ORadj 1.32 95% CI: 0.78–2.23). Cumulative exposure to enteric phthalate polymers exceeding 10,000 mg, did not reveal an association with gastric adenocarcinoma (ORadj 0.79, 95% CI: 0.54–1.16) and no association was seen for individual compounds. Additionally, no dose-response pattern was observed across exposure strata (p =.39, test for trend). Conclusion: We did not find an increased risk of gastric adenocarcinoma among Danish users of phthalate-containing drug products. Our study is limited by a low number of cases exposed to high cumulative doses of phthalates.
U2 - 10.1080/0284186X.2019.1585941
DO - 10.1080/0284186X.2019.1585941
M3 - Journal article
C2 - 30882263
AN - SCOPUS:85066503604
SN - 0284-186X
VL - 58
SP - 852
EP - 858
JO - Acta Oncologica
JF - Acta Oncologica
IS - 6
ER -