Περίληψη:
Ovarian cancer risk factors differ by histotype; however, within
subtype, there is substantial variability in outcomes. We hypothesized
that risk factor profiles may influence tumor aggressiveness, defined by
time between diagnosis and death, independent of histology. Among 1.3
million women from 21 prospective cohorts, 4,584 invasive epithelial
ovarian cancers were identified and classified as highly aggressive
(death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n
= 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and
less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox
proportional hazards regression, we assessed heterogeneity of
associations by tumor aggressiveness for all cases and among serous and
endometrioid/clear cell tumors. Associations between parity (p(het) =
0.01), family history of ovarian cancer (p(het) = 0.02), body mass index
(BMI; p(het) <= 0.04) and smoking (p(het) < 0.01) and ovarian cancer
risk differed by aggressiveness. A first/single pregnancy, relative to
nulliparity, was inversely associated with highly aggressive disease
(HR: 0.72; 95% CI [0.58-0.88]), no association was observed for
subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast,
first and subsequent pregnancies were similarly associated with less
aggressive disease (0.87 for both). Family history of ovarian cancer was
only associated with risk of less aggressive disease (1.94
[1.47-2.55]). High BMI (>= 35 vs. 20 to < 25 kg/m(2), 1.93
[1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were
associated with increased risk of highly aggressive disease. Results
were similar within histotypes. Ovarian cancer risk factors may be
directly associated with subtypes defined by tumor aggressiveness,
rather than through differential effects on histology. Studies to assess
biological pathways are warranted.
Συγγραφείς:
Fortner, Renee T.
Poole, Elizabeth M.
Wentzensen, Nicolas A. and
Trabert, Britton
White, Emily
Arslan, Alan A.
Patel, V, Alpa
and Setiawan, V. Wendy
Visvanathan, Kala
Weiderpass, Elisabete
and Adami, Hans-Olov
Black, Amanda
Bernstein, Leslie and
Brinton, Louise A.
Buring, Julie
Clendenen, V, Tess and
Fournier, Agnes
Fraser, Gary
Gapstur, Susan M.
Gaudet, Mia
M.
Giles, Graham G.
Gram, Inger T.
Hartge, Patricia and
Hoffman-Bolton, Judith
Idahl, Annika
Kaaks, Rudolf
Kirsh,
Victoria A.
Knutsen, Synnove
Koh, Woon-Puay
Lacey, Jr.,
James V.
Lee, I-Min
Lundin, Eva
Merritt, Melissa A. and
Milne, Roger L.
Onland-Moret, N. Charlotte
Peters, Ulrike and
Poynter, Jenny N.
Rinaldi, Sabina
Robien, Kim
Rohan, Thomas
and Sanchez, Maria-Jose
Schairer, Catherine
Schouten, Leo J. and
Tjonneland, Anne
Townsend, Mary K.
Travis, Ruth C. and
Trichopoulou, Antonia
van den Brandt, Piet A.
Vineis, Paolo and
Wilkens, Lynne
Wolk, Alicja
Yang, Hannah P. and
Zeleniuch-Jacquotte, Anne
Tworoger, Shelley S.
