Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study

Australian Ovarian Cancer Study Group

doi:10.1038/s41416-018-0011-3

Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study

Australian Ovarian Cancer Study Group

Department of Clinical Medicine

6 Citations (Scopus)

27 Downloads (Pure)

Abstract

BACKGROUND: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias.

METHODS: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis.

RESULTS: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours.

CONCLUSIONS: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.

Original language	English
Journal	British Journal of Cancer
Volume	118
Issue number	8
Pages (from-to)	1123-1129
Number of pages	7
ISSN	0007-0920
DOIs	https://doi.org/10.1038/s41416-018-0011-3
Publication status	Published - 1 Apr 2018

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Body Height/genetics
Carcinoma, Ovarian Epithelial/epidemiology
Case-Control Studies
Female
Genetic Predisposition to Disease
Geography
Humans
Mendelian Randomization Analysis
Middle Aged
Ovarian Neoplasms/epidemiology
Risk Factors
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

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title = "Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study",

abstract = "BACKGROUND: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias.METHODS: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis.RESULTS: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours.CONCLUSIONS: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Body Height/genetics, Carcinoma, Ovarian Epithelial/epidemiology, Case-Control Studies, Female, Genetic Predisposition to Disease, Geography, Humans, Mendelian Randomization Analysis, Middle Aged, Ovarian Neoplasms/epidemiology, Risk Factors, Young Adult",

author = "Dixon-Suen, {Suzanne C} and Nagle, {Christina M} and Thrift, {Aaron P} and Pharoah, {Paul D P} and Ailith Ewing and Pearce, {Celeste Leigh} and Wei Zheng and Georgia Chenevix-Trench and Fasching, {Peter A} and Beckmann, {Matthias W} and Diether Lambrechts and Ignace Vergote and Sandrina Lambrechts and {Van Nieuwenhuysen}, Els and Rossing, {Mary Anne} and Doherty, {Jennifer A} and Wicklund, {Kristine G} and Jenny Chang-Claude and Jung, {Audrey Y} and Moysich, {Kirsten B} and Kunle Odunsi and Goodman, {Marc T} and Wilkens, {Lynne R} and Thompson, {Pamela J} and Shvetsov, {Yurii B} and Thilo D{\"o}rk and Tjoung-Won Park-Simon and Peter Hillemanns and Natalia Bogdanova and Ralf Butzow and Heli Nevanlinna and Pelttari, {Liisa M} and Arto Leminen and Francesmary Modugno and Ness, {Roberta B} and Edwards, {Robert P} and Kelley, {Joseph L} and Florian Heitz and {du Bois}, Andreas and Philipp Harter and Ira Schwaab and Karlan, {Beth Y} and Jenny Lester and Sandra Orsulic and Rimel, {Bobbie J} and Kj{\ae}r, {Susanne K} and Estrid H{\o}gdall and Allan Jensen and H{\o}gdall, {Claus K} and Lene Lundvall and {Australian Ovarian Cancer Study Group}",

year = "2018",

month = apr,

day = "1",

doi = "10.1038/s41416-018-0011-3",

language = "English",

volume = "118",

pages = "1123--1129",

journal = "The British journal of cancer. Supplement",

issn = "0007-0920",

publisher = "nature publishing group",

number = "8",

}

TY - JOUR

T1 - Adult height is associated with increased risk of ovarian cancer

T2 - a Mendelian randomisation study

AU - Dixon-Suen, Suzanne C

AU - Nagle, Christina M

AU - Thrift, Aaron P

AU - Pharoah, Paul D P

AU - Ewing, Ailith

AU - Pearce, Celeste Leigh

AU - Zheng, Wei

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 - Jung, Audrey Y

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 - du Bois, Andreas

AU - Harter, Philipp

AU - Schwaab, Ira

AU - Karlan, Beth Y

AU - Lester, Jenny

AU - Orsulic, Sandra

AU - Rimel, Bobbie J

AU - Kjær, Susanne K

AU - Høgdall, Estrid

AU - Jensen, Allan

AU - Høgdall, Claus K

AU - Lundvall, Lene

AU - Australian Ovarian Cancer Study Group

PY - 2018/4/1

Y1 - 2018/4/1

N2 - BACKGROUND: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias.METHODS: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis.RESULTS: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours.CONCLUSIONS: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.

AB - BACKGROUND: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias.METHODS: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis.RESULTS: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours.CONCLUSIONS: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Body Height/genetics

KW - Carcinoma, Ovarian Epithelial/epidemiology

KW - Case-Control Studies

KW - Female

KW - Genetic Predisposition to Disease

KW - Geography

KW - Humans

KW - Mendelian Randomization Analysis

KW - Middle Aged

KW - Ovarian Neoplasms/epidemiology

KW - Risk Factors

KW - Young Adult

U2 - 10.1038/s41416-018-0011-3

DO - 10.1038/s41416-018-0011-3

M3 - Journal article

C2 - 29555990

SN - 0007-0920

VL - 118

SP - 1123

EP - 1129

JO - The British journal of cancer. Supplement

JF - The British journal of cancer. Supplement

IS - 8

ER -

Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study

Abstract

Keywords

UN SDGs

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