Dixon, SC;
Nagle, CM;
Thrift, AP;
Pharoah, PD;
Pearce, CL;
Zheng, W;
Painter, JN;
... Ovarian Cancer Association Consortium, .; + view all
(2016)
Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study.
International Journal of Epidemiology
, 45
(3)
pp. 884-895.
10.1093/ije/dyw158.
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Dixon et al Adult body mass index and risk of ovarian cancer by subtype -Mendelian randomization study.pdf Download (1MB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/ije/dyw158 |
| Publisher version: | http://dx.doi.org/10.1093/ije/dyw158 |
| Language: | English |
| Additional information: | Coyright © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association. This is a pre-copyedited, author-produced PDF of an article accepted for publication in the International Journal of Epidemiology, following peer review. The version of record [Suzanne C Dixon et al, Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study Int. J. Epidemiol. (2016) 45 (3): 884-895] is available online at: http://dx.doi.org/10.1093/ije/dyw158 |
| Keywords: | Body mass index, Mendelian randomization analysis, obesity, ovarian neoplasms |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1504437 |
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