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 |
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Pages (from-to) | 1123-1129 |
Number of pages | 7 |
Journal | British Journal of Cancer |
Volume | 118 |
Issue number | 8 |
DOIs | |
Publication status | Published - 1 Apr 2018 |
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Adult height is associated with increased risk of ovarian cancer : A Mendelian randomisation study. / Dixon-Suen, Suzanne C.; Nagle, Christina M.; Thrift, Aaron P.; Pharoah, Paul D.P.; Ewing, Ailith; Pearce, Celeste Leigh; Zheng, Wei; 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; Jung, Audrey Y.; 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; Du Bois, Andreas; Harter, Philipp; Schwaab, Ira; Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Rimel, Bobbie J.; Kjær, Susanne K.; Høgdall, Estrid; Jensen, Allan; Goode, Ellen L.; Fridley, Brooke L.; Cunningham, Julie M.; Winham, Stacey J.; Giles, Graham G.; Bruinsma, Fiona; Milne, Roger L.; Southey, Melissa C.; Hildebrandt, Michelle A.T.; Wu, Xifeng; Lu, Karen H.; Liang, Dong; Levine, Douglas A.; Bisogna, Maria; Schildkraut, Joellen M.; Berchuck, Andrew; Cramer, Daniel W.; Terry, Kathryn L.; Bandera, Elisa V.; Olson, Sara H.; Salvesen, Helga B.; Thomsen, Liv Cecilie Vestrheim; Kopperud, Reidun K.; Bjorge, Line; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Pejovic, Tanja; Bruegl, Amanda; Cook, Linda S.; Le, Nhu D.; Swenerton, Kenneth D.; Brooks-Wilson, Angela; Kelemen, Linda E.; Lubiński, Jan; Huzarski, Tomasz; Gronwald, Jacek; Menkiszak, Janusz; Wentzensen, Nicolas; Brinton, Louise; Yang, Hannah; Lissowska, Jolanta; Høgdall, Claus K.; Lundvall, Lene; Song, Honglin; Tyrer, Jonathan P.; Campbell, Ian; Eccles, Diana; Paul, James; Glasspool, Rosalind; Siddiqui, Nadeem; Whittemore, Alice S.; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Narod, Steven A.; Phelan, Catherine; Risch, Harvey A.; McLaughlin, John R.; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Wu, Anna H.; Pike, Malcolm C.; Tseng, Chiu Chen; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Budzilowska, Agnieszka; Rzepecka, Iwona K.; Webb, Penelope M.; on behalf of the Ovarian Cancer Association Consortium.
In: British Journal of Cancer, Vol. 118, No. 8, 01.04.2018, p. 1123-1129.Research output: Contribution to journal › Article › Research › peer-review
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 - 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 - Southey, Melissa C.
AU - Hildebrandt, Michelle A.T.
AU - Wu, Xifeng
AU - Lu, Karen H.
AU - Liang, Dong
AU - Levine, Douglas A.
AU - Bisogna, Maria
AU - Schildkraut, Joellen M.
AU - Berchuck, Andrew
AU - Cramer, Daniel W.
AU - Terry, Kathryn L.
AU - Bandera, Elisa V.
AU - Olson, Sara H.
AU - Salvesen, Helga B.
AU - Thomsen, Liv Cecilie Vestrheim
AU - Kopperud, Reidun K.
AU - Bjorge, Line
AU - Kiemeney, Lambertus A.
AU - Massuger, Leon F.A.G.
AU - Pejovic, Tanja
AU - Bruegl, Amanda
AU - Cook, Linda S.
AU - Le, Nhu D.
AU - Swenerton, Kenneth D.
AU - Brooks-Wilson, Angela
AU - Kelemen, Linda E.
AU - Lubiński, Jan
AU - Huzarski, Tomasz
AU - Gronwald, Jacek
AU - Menkiszak, Janusz
AU - Wentzensen, Nicolas
AU - Brinton, Louise
AU - Yang, Hannah
AU - Lissowska, Jolanta
AU - Høgdall, Claus K.
AU - Lundvall, Lene
AU - Song, Honglin
AU - Tyrer, Jonathan P.
AU - Campbell, Ian
AU - Eccles, Diana
AU - Paul, James
AU - Glasspool, Rosalind
AU - Siddiqui, Nadeem
AU - Whittemore, Alice S.
AU - Sieh, Weiva
AU - McGuire, Valerie
AU - Rothstein, Joseph H.
AU - Narod, Steven A.
AU - Phelan, Catherine
AU - Risch, Harvey A.
AU - McLaughlin, John R.
AU - Anton-Culver, Hoda
AU - Ziogas, Argyrios
AU - Menon, Usha
AU - Gayther, Simon A.
AU - Ramus, Susan J.
AU - Gentry-Maharaj, Aleksandra
AU - Wu, Anna H.
AU - Pike, Malcolm C.
AU - Tseng, Chiu Chen
AU - Kupryjanczyk, Jolanta
AU - Dansonka-Mieszkowska, Agnieszka
AU - Budzilowska, Agnieszka
AU - Rzepecka, Iwona K.
AU - Webb, Penelope M.
AU - on behalf of the Ovarian Cancer Association Consortium
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.
UR - http://www.scopus.com/inward/record.url?scp=85044249910&partnerID=8YFLogxK
U2 - 10.1038/s41416-018-0011-3
DO - 10.1038/s41416-018-0011-3
M3 - Article
AN - SCOPUS:85044249910
VL - 118
SP - 1123
EP - 1129
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 8
ER -