Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Adult body mass index and risk of ovarian cancer by subtype : a Mendelian randomization study. / Dixon, Suzanne C; Nagle, Christina M; Thrift, Aaron P; Pharoah, Paul Dp; Pearce, Celeste Leigh; Zheng, Wei; Painter, Jodie N; 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 Krüger; Høgdall, Estrid Vilma Solyom; Jensen, Allan; Goode, Ellen L; Fridley, Brooke L; Cunningham, Julie M; Winham, Stacey J; Giles, Graham G; Bruinsma, Fiona; Milne, Roger L; Høgdall, Claus Kim; AOCS Group & Australian Cancer Study (Ovarian Cancer).
I: International Journal of Epidemiology, Bind 45, Nr. 3, 07.2016, s. 884-895.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Adult body mass index and risk of ovarian cancer by subtype
T2 - a Mendelian randomization study
AU - Dixon, Suzanne C
AU - Nagle, Christina M
AU - Thrift, Aaron P
AU - Pharoah, Paul Dp
AU - Pearce, Celeste Leigh
AU - Zheng, Wei
AU - Painter, Jodie N
AU - Chenevix-Trench, Georgia
AU - Fasching, Peter A
AU - Beckmann, Matthias W
AU - Lambrechts, Diether
AU - Vergote, Ignace
AU - Lambrechts, Sandrina
AU - Van Nieuwenhuysen, Els
AU - Rossing, Mary Anne
AU - Doherty, Jennifer A
AU - Wicklund, Kristine G
AU - Chang-Claude, Jenny
AU - Rudolph, Anja
AU - Moysich, Kirsten B
AU - Odunsi, Kunle
AU - Goodman, Marc T
AU - Wilkens, Lynne R
AU - Thompson, Pamela J
AU - Shvetsov, Yurii B
AU - Dörk, Thilo
AU - Park-Simon, Tjoung-Won
AU - Hillemanns, Peter
AU - Bogdanova, Natalia
AU - Butzow, Ralf
AU - Nevanlinna, Heli
AU - Pelttari, Liisa M
AU - Leminen, Arto
AU - Modugno, Francesmary
AU - Ness, Roberta B
AU - Edwards, Robert P
AU - Kelley, Joseph L
AU - Heitz, Florian
AU - Karlan, Beth Y
AU - Kjær, Susanne Krüger
AU - Høgdall, Estrid Vilma Solyom
AU - Jensen, Allan
AU - Goode, Ellen L
AU - Fridley, Brooke L
AU - Cunningham, Julie M
AU - Winham, Stacey J
AU - Giles, Graham G
AU - Bruinsma, Fiona
AU - Milne, Roger L
AU - Høgdall, Claus Kim
AU - AOCS Group & Australian Cancer Study (Ovarian Cancer)
N1 - © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
PY - 2016/7
Y1 - 2016/7
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1093/ije/dyw158
DO - 10.1093/ije/dyw158
M3 - Journal article
C2 - 27401727
VL - 45
SP - 884
EP - 895
JO - International Journal of Epidemiology
JF - International Journal of Epidemiology
SN - 0300-5771
IS - 3
ER -
ID: 167590536