Long-chain ω-3 fatty acid intake and endometrial cancer risk in the Women's Health Initiative.
BACKGROUND
Inflammation may be important in endometrial cancer development. Long-chain ω-3 (n-3) polyunsaturated fatty acids (LCω-3PUFAs) may reduce inflammation and, therefore, reduce cancer risk. Because body mass is associated with both inflammation and endometrial cancer risk, it may modify the association of fat intake on risk.


OBJECTIVE
We examined whether intakes of LCω-3PUFAs were associated with endometrial cancer risk overall and stratified by body size and histologic subtype.


METHODS
Women were n = 87,360 participants of the Women's Health Initiative Observational Study and Clinical Trials who were aged 50-79 y, had an intact uterus, and completed a baseline food-frequency questionnaire. After 13 y of follow-up, n = 1253 incident invasive endometrial cancers were identified. Cox regression models were used to estimate HRs and 95% CIs for the association of intakes of individual ω-3 fatty acids and fish with endometrial cancer risk.


RESULTS
Intakes of individual LCω-3PUFAs were associated with 15-23% linear reductions in endometrial cancer risk. In women with body mass index (BMI; in kg/m(2)) <25, those in the upper compared with lowest quintiles of total LCω-3PUFA intake (sum of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) had significantly reduced endometrial cancer risk (HR: 0.59; 95% CI: 0.40, 0.82; P-trend = 0.001), whereas there was little evidence of an association in overweight or obese women. The reduction in risk observed in normal-weight women was further specific to type I cancers.


CONCLUSIONS
Long-chain ω-3 intake was associated with reduced endometrial cancer risk only in normal-weight women. Additional studies that use biomarkers of ω-3 intake are needed to more accurately estimate their effects on endometrial cancer risk. This trial was registered at clinicaltrials.gov as NCT00000611.
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
Theodore M
TM
Brasky
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
Rebecca J
RJ
Rodabough
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
Jingmin
J
Liu
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
Michelle L
ML
Kurta
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
Lauren A
LA
Wise
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
Tonya S
TS
Orchard
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
David E
DE
Cohn
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
Martha A
MA
Belury
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
Emily
E
White
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
JoAnn E
JE
Manson
From the Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine (TMB), the Department of Human Sciences, College of Education and Human Ecology (TSO and MAB), and the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine (DEC), The Ohio State University, Columbus, OH; the Women's Health Initiative Clinical Coordinating Center(RJR and JL) and the Cancer Prevention Program (EW and MLN), Fred Hutchinson Cancer Research Center, Seattle, WA; the Office of Epidemiology and Biostatistics, Allegheny County Health Department, Pittsburgh, PA (MLK); the Department of Epidemiology, Slone Epidemiology Center at Boston University, Boston University School of Public Health, Boston, MA (LAW); and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (JEM).
Marian L
ML
Neuhouser
D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage; D016889:Endometrial Neoplasms / Q000517:prevention & control*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy; D064887:Observational Studies as Topic; D050177:Overweight / Q000188:drug therapy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016387:Women's Health
D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
docosahexaenoic acid; eicosapentaenoic acid; endometrial cancer; fish; omega-3