TY - JOUR

T1 - Ovarian Cancer Risk Factor Associations by Primary Anatomic Site

T2 - The Ovarian Cancer Cohort Consortium

AU - Fortner, Renee T.

AU - Rice, Megan S.

AU - Knutsen, Synnove F.

AU - Orlich, Michael J.

AU - Visvanathan, Kala

AU - Patel, Alpa

AU - Gaudet, Mia M.

AU - Tjønneland, Anne

AU - Kvaskoff, Marina

AU - Kaaks, Rudolf

AU - Trichopolou, Antonia

AU - Pala, Valeria

AU - Onland-Moret, N. Charlotte

AU - Gram, Inger T.

AU - Amiano, Pilar

AU - Idahl, Annika

AU - Allen, Naomi E.

AU - Weiderpass, Elisabete

AU - Poynter, Jenny N.

AU - Robien, Kim

AU - Giles, Graham G.

AU - Milne, Roger L.

AU - Setiawan, Veronica W.

AU - Merritt, Melissa A.

AU - van den Brandt, Piet A.

AU - Zeleniuch-Jacquotte, Anne

AU - Arslan, Alan A.

AU - O'Brien, Katie M.

AU - Sandler, Dale P.

AU - Wolk, Alicja

AU - Hakansson, Niclas

AU - Harris, Holly R.

AU - Trabert, Britton

AU - Wentzensen, Nicolas

AU - Tworoger, Shelley S.

AU - Schouten, Leo J.

PY - 2020

Y1 - 2020

N2 - Background: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites.Methods: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests.Results: Most associations did not vary by tumor site (P-het = 0.05). Associations between first pregnancy (P-het = 0.04), tubal ligation (P-het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P-het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P-het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases.Conclusions: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site.Impact: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

AB - Background: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites.Methods: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests.Results: Most associations did not vary by tumor site (P-het = 0.05). Associations between first pregnancy (P-het = 0.04), tubal ligation (P-het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P-het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P-het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases.Conclusions: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site.Impact: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

KW - EPITHELIAL OVARIAN

KW - PRIMARY PERITONEAL

KW - FALLOPIAN-TUBE

KW - CARCINOMA

KW - SUBTYPES

KW - WOMEN

KW - MARKERS

U2 - 10.1158/1055-9965.EPI-20-0354

DO - 10.1158/1055-9965.EPI-20-0354

M3 - Journal article

C2 - 32732252

VL - 29

SP - 2010

EP - 2018

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 10

ER -