Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study

被引：61

作者：

Dixon, Suzanne C. ^{[1
,2
]}

Nagle, Christina M. ^{[1
,2
]}

Thrift, Aaron P. ^{[3
,4
]}

Pharoah, Paul D. P. ^{[5
]}

Pearce, Celeste Leigh ^{[6
,7
]}

Zheng, Wei ^{[8
]}

Painter, Jodie N. ^{[9
]}

Chenevix-Trench, Georgia ^{[10
]}

Fasching, Peter A. ^{[11
,12
]}

Beckmann, Matthias W. ^{[12
]}

Lambrechts, Diether ^{[13
,14
]}

Vergote, Ignace ^{[15
,16
]}

Lambrechts, Sandrina ^{[15
,16
]}

Van Nieuwenhuysen, Els ^{[15
,16
]}

Rossing, Mary Anne ^{[17
,18
]}

Doherty, Jennifer A. ^{[19
]}

Wicklund, Kristine G. ^{[17
]}

Chang-Claude, Jenny ^{[20
]}

Rudolph, Anja ^{[20
]}

Moysich, Kirsten B. ^{[21
]}

Odunsi, Kunle ^{[22
]}

Goodman, Marc T. ^{[23
,24
]}

Wilkens, Lynne R. ^{[25
]}

Thompson, Pamela J. ^{[23
]}

Shvetsov, Yurii B. ^{[25
]}

Doerk, Thilo ^{[26
,27
]}

Park-Simon, Tjoung-Won ^{[26
,27
]}

Hillemanns, Peter ^{[26
,27
]}

Bogdanova, Natalia ^{[28
]}

Butzow, Ralf ^{[29
,30
]}

Nevanlinna, Heli ^{[30
,31
]}

Pelttari, Liisa M. ^{[30
,31
]}

Leminen, Arto ^{[30
,31
]}

Modugno, Francesmary ^{[32
,33
,34
,35
]}

Ness, Roberta B. ^{[36
]}

Edwards, Robert P. ^{[32
,33
,34
]}

Kelley, Joseph L. ^{[32
]}

Heitz, Florian ^{[37
,38
]}

Karlan, Beth Y. ^{[39
]}

Kjaer, Susanne K. ^{[40
,41
]}

Hogdall, Estrid ^{[40
,42
]}

Jensen, Allan ^{[40
]}

Goode, Ellen L. ^{[43
]}

Fridley, Brooke L. ^{[44
]}

Cunningham, Julie M. ^{[45
]}

Winham, Stacey J. ^{[46
]}

Giles, Graham G. ^{[47
,48
,49
]}

Bruinsma, Fiona ^{[47
]}

Milne, Roger L. ^{[47
,48
]}

Southey, Melissa C. ^{[50
]}

机构：

[1] QIMR Berghofer Med Res Inst, Gynaecol Canc Grp, Brisbane, Qld, Australia

[2] Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia

[3] Baylor Coll Med, Dept Med, Houston, TX 77030 USA

[4] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

[5] Univ Cambridge, Ctr Canc Genet Epidemiol, Cambridge, England

[6] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA

[7] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA

[8] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA

[9] QIMR Berghofer Med Res Inst, Mol Canc Epidemiol Grp, Brisbane, Qld, Australia

[10] QIMR Berghofer Med Res Inst, Canc Genet Grp, Brisbane, Qld, Australia

[11] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA

[12] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen Nuremberg, Dept Gynecol & Obstet, Univ Hosp Erlangen, Erlangen, Germany

[13] VIB, Vesalius Res Ctr, Leuven, Belgium

[14] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium

[15] Univ Hosp Leuven, Dept Obstet & Gynaecol, Div Gynecol Oncol, Leuven, Belgium

[16] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium

[17] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA

[18] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[19] Geisel Sch Med Dartmouth, Dept Epidemiol, Hanover, NH USA

[20] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[21] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA

[22] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA

[23] Cedars Sinai Med Ctr, Canc Prevent & Control, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA

[24] Cedars Sinai Med Ctr, Dept Biomed Sci, Community & Populat Hlth Res Inst, Los Angeles, CA 90048 USA

[25] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA

[26] Hannover Med Sch, Clin Obstet, Hannover, Germany

[27] Hannover Med Sch, Clin Gynaecol, Hannover, Germany

[28] Hannover Med Sch, Radiat Oncol Res Unit, Hannover, Germany

[29] Univ Helsinki, Dept Pathol, Helsinki, Finland

[30] Helsinki Univ Hosp, Helsinki, Finland

[31] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland

[32] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA

[33] Magee Womens Res Inst, Womens Canc Res Program, Ovarian Canc Ctr Excellence, Pittsburgh, PA USA

[34] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA

[35] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA

[36] Univ Texas Sch Publ Hlth, Houston, TX USA

[37] Knappschaft GmbH, Evang Huyssens Stiftung, Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, Essen, Germany

[38] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany

[39] Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA

[40] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark

[41] Univ Copenhagen, Rigshosp, Dept Gynaecol, Copenhagen, Denmark

[42] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark

[43] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA

[44] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA

[45] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[46] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA

[47] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

[48] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia

[49] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia

[50] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia

来源：

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY | 2016年 / 45卷 / 03期

基金：

英国医学研究理事会; 美国国家卫生研究院; 加拿大健康研究院;

关键词：

Body mass index; obesity; ovarian neoplasms; Mendelian randomization analysis; CAUSAL INFERENCE; METAANALYSIS; REGRESSION; OBESITY; SUSCEPTIBILITY; INSTRUMENTS;

D O I：

10.1093/ije/dyw158

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

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 metaanalysis. 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.

引用

页码：884 / 895

页数：12

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