Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study.
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Dixon Suzanne C, Nagle Christina M, Thrift Aaron P, Pharoah Paul Dp, Pearce Celeste Leigh, Zheng Wei, Painter Jodie N, AOCS Group & Australian Cancer Study (Ovarian Cancer), Chenevix-Trench Georgia, Fasching Peter A, Beckmann Matthias W, Lambrechts Diether, Vergote Ignace, Lambrechts Sandrina, Van Nieuwenhuysen Els, Rossing Mary Anne, Doherty Jennifer A, Wicklund Kristine G, Chang-Claude Jenny, Rudolph Anja, Moysich Kirsten B, Odunsi Kunle, Goodman Marc T, Wilkens Lynne R, Thompson Pamela J, Shvetsov Yurii B, Dörk Thilo, Park-Simon Tjoung-Won, Hillemanns Peter, Bogdanova Natalia, Butzow Ralf, Nevanlinna Heli, Pelttari Liisa M, Leminen Arto, Modugno Francesmary, Ness Roberta B, Edwards Robert P, Kelley Joseph L, Heitz Florian, Karlan Beth Y, Kjær Susanne K, Høgdall Estrid, Jensen Allan, Goode Ellen L, Fridley Brooke L, Cunningham Julie M, Winham Stacey J, Giles Graham G, Bruinsma Fiona, Milne Roger L, Southey Melissa C, Hildebrandt Michelle A T, Wu Xifeng, Lu Karen H, Liang Dong, Levine Douglas A, Bisogna Maria, Schildkraut Joellen M, Berchuck Andrew, Cramer Daniel W, Terry Kathryn L, Bandera Elisa V, Olson Sara H, Salvesen Helga B, Thomsen Liv Cecilie, Kopperud Reidun K, Bjorge Line, Kiemeney Lambertus A, Massuger Leon F A G, Pejovic Tanja, Cook Linda S, Le Nhu D, Swenerton Kenneth D, Brooks-Wilson Angela, Kelemen Linda E, Lubiński Jan, Huzarski Tomasz, Gronwald Jacek, Menkiszak Janusz, Wentzensen Nicolas, Brinton Louise, Yang Hannah, Lissowska Jolanta, Høgdall Claus K, Lundvall Lene, Song Honglin, Tyrer Jonathan P, Campbell Ian, Eccles Diana, Paul James, Glasspool Rosalind, Siddiqui Nadeem, Whittemore Alice S, Sieh Weiva, McGuire Valerie, Rothstein Joseph H, Narod Steven A, Phelan Catherine, Risch Harvey A, McLaughlin John R, Anton-Culver Hoda, Ziogas Argyrios, Menon Usha, Gayther Simon A, Ramus Susan J, Gentry-Maharaj Aleksandra, Wu Anna H, Pike Malcolm C, Tseng Chiu-Chen, Kupryjanczyk Jolanta, Dansonka-Mieszkowska Agnieszka, Budzilowska Agnieszka, Spiewankiewicz Beata, Webb Penelope M, Ovarian Cancer Association Consortium
Аннотация
METHODS: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis.
RESULTS: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81).
CONCLUSIONS: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence.