| Autor: |
Usha Menon, Anna H. Wu, Suzanne C. Dixon, Chiu-Chen Tseng, Dong Liang, Simon A. Gayther, Andrew Berchuck, Peter A. Fasching, Harvey A. Risch, Georgia Chenevix-Trench, Brooke L. Fridley, Joseph L. Kelley, Jennifer A. Doherty, Leon F.A.G. Massuger, Tjoung-Won Park-Simon, Mary Anne Rossing, Thilo Dörk, Douglas A. Levine, Kenneth D. Swenerton, Jodie N. Painter, Tanja Pejovic, Florian Heitz, Catherine M. Phelan, Beth Y. Karlan, Liisa M. Pelttari, Pamela J. Thompson, Beata Spiewankiewicz, Lene Lundvall, Agnieszka Dansonka-Mieszkowska, Melissa C. Southey, Liv Cecilie Vestrheim Thomsen, Els Van Nieuwenhuysen, Fiona Bruinsma, Robert P. Edwards, Weiva Sieh, Natalia Bogdanova, Helga B. Salvesen, Diether Lambrechts, Christina M. Nagle, Jolanta Kupryjanczyk, Nicolas Wentzensen, Jacek Gronwald, Alice S. Whittemore, Karen H. Lu, Kunle Odunsi, Line Bjørge, Paul D.P. Pharoah, Kathryn L. Terry, Lambertus A. Kiemeney, Claus Høgdall, Steven A. Narod, Aaron P. Thrift, Diana Eccles, Daniel W. Cramer, Ignace Vergote, Linda S. Cook, Estrid Høgdall, John R. McLaughlin, Malcolm C. Pike, Matthias W. Beckmann, Peter Hillemanns, Anja Rudolph, Roger L. Milne, Maria Bisogna, Sandrina Lambrechts, Ralf Bützow, Francesmary Modugno, Stacey J. Winham, Jan Lubinski, Joseph H. Rothstein, Michelle A.T. Hildebrandt, Heli Nevanlinna, Reidun K. Kopperud, Jolanta Lissowska, Tomasz Huzarski, Arto Leminen, Nadeem Siddiqui, Hannah P. Yang, Graham G. Giles, Janusz Menkiszak, Agnieszka Budzilowska, Louise A. Brinton, Valerie McGuire, Celeste Leigh Pearce, Ian G. Campbell, Hoda Anton-Culver, Kristine G. Wicklund, Susanne K. Kjaer, Marc T. Goodman, Roberta B. Ness, James Paul, Argyrios Ziogas, Linda E. Kelemen, Elisa V. Bandera, Honglin Song, Julie M. Cunningham, Allan Jensen, Nhu D. Le, Wei Zheng, Kirsten B. Moysich, Jonathan Tyrer, Penelope M. Webb, Sara H. Olson, Lynne R. Wilkens, Angela Brooks-Wilson, Xifeng Wu, Rosalind Glasspool, Susan J. Ramus, Yurii B. Shvetsov, Joellen M. Schildkraut, Aleksandra Gentry-Maharaj, Jenny Chang-Claude, Ellen L. Goode |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
International Journal of Epidemiology, 45, 3, pp. 884-95
International Journal of Epidemiology, 45, 884-95 |
| ISSN: |
0300-5771 |
| DOI: |
10.1093/ije/dyw158 |
| Popis: |
Contains fulltext : 170949.pdf (Publisher’s version ) (Closed access) BACKGROUND: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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