Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium

P M Webb¹, R Na², E Weiderpass³, H O Adami⁴, K E Anderson⁵, K A Bertrand⁶, E Botteri⁷, T M Brasky⁸, L A Brinton⁹, C Chen¹⁰, J A Doherty¹¹, L Lu¹², S E McCann¹³, K B Moysich¹³, S Olson¹⁴, S Petruzella¹⁴, J R Palmer⁶, A E Prizment⁵, C Schairer⁹, V W Setiawan¹⁵, A B Spurdle², B Trabert⁹, N Wentzensen⁹, L Wilkens¹⁶, H P Yang⁹, H Yu¹⁶, H A Risch¹², S J Jordan¹⁷

Affiliations

¹ Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Public Health, University of Queensland, Brisbane, Australia. Electronic address: penny.webb@qimrberghofer.edu.au.
² Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway; Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland; Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway.
⁵ School of Public Health, University of Minnesota, Minneapolis, USA.
⁶ Slone Epidemiology Center, Boston University, Boston, USA.
⁷ Women and Children's Division, Norwegian National Advisory Unit on Women's Health, Oslo University Hospital, Oslo, Norway; Department of Bowel Cancer Screening, Cancer Registry of Norway, Oslo, Norway.
⁸ Ohio State University Comprehensive Cancer Center, Columbus, USA.
⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA.
¹⁰ Fred Hutchinson Cancer Research Center, Seattle, USA.
¹¹ Fred Hutchinson Cancer Research Center, Seattle, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, USA; Department of Population Health Sciences, University of Utah, Salt Lake City, USA.
¹² Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, USA.
¹³ Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, USA.
¹⁴ Memorial Sloan Kettering Cancer Center, New York, USA.
¹⁵ University of Southern California, Los Angeles, USA.
¹⁶ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, USA.
¹⁷ Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Public Health, University of Queensland, Brisbane, Australia.

PMID: 30566587
PMCID: PMC6386026
DOI: 10.1093/annonc/mdy541

Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium

P M Webb et al. Ann Oncol. 2019.

. 2019 Feb 1;30(2):310-316.

doi: 10.1093/annonc/mdy541.

Authors

Affiliations

¹ Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Public Health, University of Queensland, Brisbane, Australia. Electronic address: penny.webb@qimrberghofer.edu.au.
² Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway; Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland; Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway.
⁵ School of Public Health, University of Minnesota, Minneapolis, USA.
⁶ Slone Epidemiology Center, Boston University, Boston, USA.
⁷ Women and Children's Division, Norwegian National Advisory Unit on Women's Health, Oslo University Hospital, Oslo, Norway; Department of Bowel Cancer Screening, Cancer Registry of Norway, Oslo, Norway.
⁸ Ohio State University Comprehensive Cancer Center, Columbus, USA.
⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA.
¹⁰ Fred Hutchinson Cancer Research Center, Seattle, USA.
¹¹ Fred Hutchinson Cancer Research Center, Seattle, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, USA; Department of Population Health Sciences, University of Utah, Salt Lake City, USA.
¹² Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, USA.
¹³ Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, USA.
¹⁴ Memorial Sloan Kettering Cancer Center, New York, USA.
¹⁵ University of Southern California, Los Angeles, USA.
¹⁶ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, USA.
¹⁷ Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Public Health, University of Queensland, Brisbane, Australia.

PMID: 30566587
PMCID: PMC6386026
DOI: 10.1093/annonc/mdy541

Abstract

Background: Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited.

Patients and methods: We pooled individual-level data from seven cohort and five case-control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect.

Results: At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 [95% CI 0.76-0.98] and 0.86 [95% CI 0.76-0.97], respectively, for aspirin; 0.87 [95% CI 0.76-1.00] and 0.84 [0.74-0.96], respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index < 25 kg/m2, Pheterogeneity = 0.04 for aspirin, Pheterogeneity = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2-6 times/week (OR = 0.81, 95% CI 0.68-0.96) than for daily use (0.91, 0.80-1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen.

Conclusion: Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.

Keywords: acetaminophen; aspirin; endometrial cancer; nonsteroidal anti-inflammatory drugs.

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Figures

**Figure 1.**
Forest plots showing adjusted estimates and 95% confidence intervals (CIs) for the association between regular use of aspirin and risk of endometrial cancer (A) overall, by study design with estimates ordered from smallest to largest and (B) stratified by participant characteristics and tumor type. The size of the box indicates the weight of the study, the line represents the 95% CI and the diamonds represent the pooled estimates. OR, odds ratio; EDGE, Estrogen, Diet, Genetics and Endometrial Cancer Study; ANECS, The Australian National Endometrial Cancer Study; FHCRC, Fred Hutchinson Cancer Research Center Study; CONN, Connecticut Endometrial Cancer Study; PEDS, Patient Epidemiologic Data System; BWHS, Black Women’s Health Study; NIH, NIH AARP Diet and Health Study; IOWA, Iowa Women’s Health Study; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; MEC, Multiethnic Cohort Study; SWLHS, Swedish Women's Lifestyle and Health Study; BCDDP, Breast Cancer Detection Demonstration Project.

**Figure 2.**
Forest plots showing adjusted estimates and 95% confidence intervals (CIs) for the association between regular use of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of endometrial cancer (A) overall, by study design with estimates ordered from smallest to largest and (B) stratified by participant characteristics and tumor type. The size of the box indicates the weight of the study, the line represents the 95% CI and the diamonds represent the pooled estimates. BMI, body mass index; pOR, pooled odds ratios; EDGE, Estrogen, Diet, Genetics and Endometrial Cancer Study; ANECS, The Australian National Endometrial Cancer Study; FHCRC, Fred Hutchinson Cancer Research Center Study; CONN, Connecticut Endometrial Cancer Study; PEDS, Patient Epidemiologic Data System; BWHS, Black Women’s Health Study; NIH, NIH AARP Diet and Health Study; IOWA, Iowa Women’s Health Study; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; MEC, Multiethnic Cohort Study; SWLHS, Swedish Women's Lifestyle and Health Study; BCDDP, Breast Cancer Detection Demonstration Project.

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References

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Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium

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Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium

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