Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent
Background Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmen...
Gespeichert in:
| Veröffentlicht in: | PLoS Medicine 2016, Vol.13 (8) |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Report |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 8 |
| container_start_page | |
| container_title | PLoS Medicine |
| container_volume | 13 |
| creator | Guo, Yan Warren Andersen, Shaneda Michailidou, Kyriaki Bolla, Manjeet K Wang, Qin Garcia-Closas, Montserrat Milne, Roger L Schmidt, Marjanka K Chang-Claude, Jenny Dunning, Allison Bojesen, Stig E Ahsan, Habibul Aittomäki, Kristiina Andrulis, Irene L Arndt, Volker Beckmann, Matthias W Beeghly-Fadiel, Alicia Benitez, Javier Bonanni, Bernardo Børresen-Dale, Anne-Lise Brand, Judith Brauch, Hiltrud Brenner, Hermann Brüning, Thomas Burwinkel, Barbara Casey, Graham Chenevix-Trench, Georgia Cox, Angela Cross, Simon S Czene, Kamila Devilee, Peter Dörk, Thilo Dumont, Ma Fasching, Peter A Figueroa, Jonine Flesch-Janys, Dieter Fletcher, Olivia Flyger, Henrik Fostira, Florentia Gammon, Marilie Giles, Graham G Guénel, Pascal Haiman, Christopher A Hamann, Ute Hooning, Maartje J Hopper, John L Jakubowska, Anna Jasmine, Farzana Jenkins, Mark John, Esther M Johnson, Nichola Jones, Michael E Kabisch, Maria Kibriya, Muhammad Knight, Julia A Koppert, Linetta B Kristensen, Vessela Le Marchand, Loic Lee, Eunjung Li, Jingmei Lindblom, Annika Luben, Robert Malone, Kathi E Mannermaa, Arto Margolin, Sara Marme, Frederik McLean, Catriona Meijers-Heijboer, Hanne Meindl, Alfons Neuhausen, Susan L Nevanlinna, Heli Neven, Patrick Perez, Jose I. A Perkins, Barbara Peterlongo, Paolo Phillips, Kelly-Anne Pylkäs, Katri Rudolph, Anja Sawyer, Elinor J Schmutzler, Rita K Seynaeve, Caroline Shah, Mitul Shrubsole, Martha J Southey, Melissa C Swerdlow, Anthony J Tomlinson, Ian Torres, Diana Truong, Thérèse Ursin, Giske Van Der Luijt, Rob B Verhoef, Senno Whittemore, Alice S Winqvist, Robert Zhao, Shilin Hall, Per Simard, Jacques Kraft, Peter Pharoah, Paul Hunter, David Zheng, Wei |
| description | Background Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. Methods We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. Results In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m.sup.2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 x 10.sup.-10). The associations were similar for both premenopausal (OR = 0.44, 95% CI:0.31-0.62, p = 9.91 x 10.sup.-8) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46-0.71, p = 1.88 x 10.sup.-8). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60-0.84, p = 1.64 x 10.sup.-7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p < 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. Conclusions BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship |
| doi_str_mv | 10.1371/journal.pmed.1002105 |
| format | Report |
| fullrecord | <record><control><sourceid>gale</sourceid><recordid>TN_cdi_gale_infotracacademiconefile_A479413889</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A479413889</galeid><sourcerecordid>A479413889</sourcerecordid><originalsourceid>FETCH-gale_infotracacademiconefile_A4794138893</originalsourceid><addsrcrecordid>eNqVjs1KAzEUhbNQsP68gYv7AHZMOjNM4662tbooSBFcyiW5I6mZm5Kk4PgOvrMRfAE5iwPfOQeOENdKVqru1O0-HCOjrw4D2UpJOVOyPRET1TZ6qmZddybOU9oXrqWWE_G9IabsDHo_wnMk60wmC_fBjrDFlOCJLX0CcmGRMGVYIhuKsHPp4w62VGLvkGFXKmFwX5hdYFiUC2OiBKGHFWaEPoYBVNPeSCnhNQzEv9H6GMOBynpFyRDnS3Hao0909ecXonpYvywfp-_o6c1xH3JEU2RpcCYw9a7wRdPpRtXzua7_PfgBtI5ixQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>report</recordtype></control><display><type>report</type><title>Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent</title><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Public Library of Science (PLoS)</source><creator>Guo, Yan ; Warren Andersen, Shaneda ; Michailidou, Kyriaki ; Bolla, Manjeet K ; Wang, Qin ; Garcia-Closas, Montserrat ; Milne, Roger L ; Schmidt, Marjanka K ; Chang-Claude, Jenny ; Dunning, Allison ; Bojesen, Stig E ; Ahsan, Habibul ; Aittomäki, Kristiina ; Andrulis, Irene L ; Arndt, Volker ; Beckmann, Matthias W ; Beeghly-Fadiel, Alicia ; Benitez, Javier ; Bonanni, Bernardo ; Børresen-Dale, Anne-Lise ; Brand, Judith ; Brauch, Hiltrud ; Brenner, Hermann ; Brüning, Thomas ; Burwinkel, Barbara ; Casey, Graham ; Chenevix-Trench, Georgia ; Cox, Angela ; Cross, Simon S ; Czene, Kamila ; Devilee, Peter ; Dörk, Thilo ; Dumont, Ma ; Fasching, Peter A ; Figueroa, Jonine ; Flesch-Janys, Dieter ; Fletcher, Olivia ; Flyger, Henrik ; Fostira, Florentia ; Gammon, Marilie ; Giles, Graham G ; Guénel, Pascal ; Haiman, Christopher A ; Hamann, Ute ; Hooning, Maartje J ; Hopper, John L ; Jakubowska, Anna ; Jasmine, Farzana ; Jenkins, Mark ; John, Esther M ; Johnson, Nichola ; Jones, Michael E ; Kabisch, Maria ; Kibriya, Muhammad ; Knight, Julia A ; Koppert, Linetta B ; Kristensen, Vessela ; Le Marchand, Loic ; Lee, Eunjung ; Li, Jingmei ; Lindblom, Annika ; Luben, Robert ; Malone, Kathi E ; Mannermaa, Arto ; Margolin, Sara ; Marme, Frederik ; McLean, Catriona ; Meijers-Heijboer, Hanne ; Meindl, Alfons ; Neuhausen, Susan L ; Nevanlinna, Heli ; Neven, Patrick ; Perez, Jose I. A ; Perkins, Barbara ; Peterlongo, Paolo ; Phillips, Kelly-Anne ; Pylkäs, Katri ; Rudolph, Anja ; Sawyer, Elinor J ; Schmutzler, Rita K ; Seynaeve, Caroline ; Shah, Mitul ; Shrubsole, Martha J ; Southey, Melissa C ; Swerdlow, Anthony J ; Tomlinson, Ian ; Torres, Diana ; Truong, Thérèse ; Ursin, Giske ; Van Der Luijt, Rob B ; Verhoef, Senno ; Whittemore, Alice S ; Winqvist, Robert ; Zhao, Shilin ; Hall, Per ; Simard, Jacques ; Kraft, Peter ; Pharoah, Paul ; Hunter, David ; Zheng, Wei</creator><creatorcontrib>Guo, Yan ; Warren Andersen, Shaneda ; Michailidou, Kyriaki ; Bolla, Manjeet K ; Wang, Qin ; Garcia-Closas, Montserrat ; Milne, Roger L ; Schmidt, Marjanka K ; Chang-Claude, Jenny ; Dunning, Allison ; Bojesen, Stig E ; Ahsan, Habibul ; Aittomäki, Kristiina ; Andrulis, Irene L ; Arndt, Volker ; Beckmann, Matthias W ; Beeghly-Fadiel, Alicia ; Benitez, Javier ; Bonanni, Bernardo ; Børresen-Dale, Anne-Lise ; Brand, Judith ; Brauch, Hiltrud ; Brenner, Hermann ; Brüning, Thomas ; Burwinkel, Barbara ; Casey, Graham ; Chenevix-Trench, Georgia ; Cox, Angela ; Cross, Simon S ; Czene, Kamila ; Devilee, Peter ; Dörk, Thilo ; Dumont, Ma ; Fasching, Peter A ; Figueroa, Jonine ; Flesch-Janys, Dieter ; Fletcher, Olivia ; Flyger, Henrik ; Fostira, Florentia ; Gammon, Marilie ; Giles, Graham G ; Guénel, Pascal ; Haiman, Christopher A ; Hamann, Ute ; Hooning, Maartje J ; Hopper, John L ; Jakubowska, Anna ; Jasmine, Farzana ; Jenkins, Mark ; John, Esther M ; Johnson, Nichola ; Jones, Michael E ; Kabisch, Maria ; Kibriya, Muhammad ; Knight, Julia A ; Koppert, Linetta B ; Kristensen, Vessela ; Le Marchand, Loic ; Lee, Eunjung ; Li, Jingmei ; Lindblom, Annika ; Luben, Robert ; Malone, Kathi E ; Mannermaa, Arto ; Margolin, Sara ; Marme, Frederik ; McLean, Catriona ; Meijers-Heijboer, Hanne ; Meindl, Alfons ; Neuhausen, Susan L ; Nevanlinna, Heli ; Neven, Patrick ; Perez, Jose I. A ; Perkins, Barbara ; Peterlongo, Paolo ; Phillips, Kelly-Anne ; Pylkäs, Katri ; Rudolph, Anja ; Sawyer, Elinor J ; Schmutzler, Rita K ; Seynaeve, Caroline ; Shah, Mitul ; Shrubsole, Martha J ; Southey, Melissa C ; Swerdlow, Anthony J ; Tomlinson, Ian ; Torres, Diana ; Truong, Thérèse ; Ursin, Giske ; Van Der Luijt, Rob B ; Verhoef, Senno ; Whittemore, Alice S ; Winqvist, Robert ; Zhao, Shilin ; Hall, Per ; Simard, Jacques ; Kraft, Peter ; Pharoah, Paul ; Hunter, David ; Zheng, Wei</creatorcontrib><description>Background Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. Methods We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. Results In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m.sup.2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 x 10.sup.-10). The associations were similar for both premenopausal (OR = 0.44, 95% CI:0.31-0.62, p = 9.91 x 10.sup.-8) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46-0.71, p = 1.88 x 10.sup.-8). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60-0.84, p = 1.64 x 10.sup.-7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p < 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. Conclusions BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.</description><identifier>ISSN: 1549-1277</identifier><identifier>DOI: 10.1371/journal.pmed.1002105</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Body mass index ; Breast cancer ; Genetic aspects ; Health aspects ; Postmenopausal women ; Risk factors ; Single nucleotide polymorphisms</subject><ispartof>PLoS Medicine, 2016, Vol.13 (8)</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>776,780,860,4476,27902</link.rule.ids></links><search><creatorcontrib>Guo, Yan</creatorcontrib><creatorcontrib>Warren Andersen, Shaneda</creatorcontrib><creatorcontrib>Michailidou, Kyriaki</creatorcontrib><creatorcontrib>Bolla, Manjeet K</creatorcontrib><creatorcontrib>Wang, Qin</creatorcontrib><creatorcontrib>Garcia-Closas, Montserrat</creatorcontrib><creatorcontrib>Milne, Roger L</creatorcontrib><creatorcontrib>Schmidt, Marjanka K</creatorcontrib><creatorcontrib>Chang-Claude, Jenny</creatorcontrib><creatorcontrib>Dunning, Allison</creatorcontrib><creatorcontrib>Bojesen, Stig E</creatorcontrib><creatorcontrib>Ahsan, Habibul</creatorcontrib><creatorcontrib>Aittomäki, Kristiina</creatorcontrib><creatorcontrib>Andrulis, Irene L</creatorcontrib><creatorcontrib>Arndt, Volker</creatorcontrib><creatorcontrib>Beckmann, Matthias W</creatorcontrib><creatorcontrib>Beeghly-Fadiel, Alicia</creatorcontrib><creatorcontrib>Benitez, Javier</creatorcontrib><creatorcontrib>Bonanni, Bernardo</creatorcontrib><creatorcontrib>Børresen-Dale, Anne-Lise</creatorcontrib><creatorcontrib>Brand, Judith</creatorcontrib><creatorcontrib>Brauch, Hiltrud</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Brüning, Thomas</creatorcontrib><creatorcontrib>Burwinkel, Barbara</creatorcontrib><creatorcontrib>Casey, Graham</creatorcontrib><creatorcontrib>Chenevix-Trench, Georgia</creatorcontrib><creatorcontrib>Cox, Angela</creatorcontrib><creatorcontrib>Cross, Simon S</creatorcontrib><creatorcontrib>Czene, Kamila</creatorcontrib><creatorcontrib>Devilee, Peter</creatorcontrib><creatorcontrib>Dörk, Thilo</creatorcontrib><creatorcontrib>Dumont, Ma</creatorcontrib><creatorcontrib>Fasching, Peter A</creatorcontrib><creatorcontrib>Figueroa, Jonine</creatorcontrib><creatorcontrib>Flesch-Janys, Dieter</creatorcontrib><creatorcontrib>Fletcher, Olivia</creatorcontrib><creatorcontrib>Flyger, Henrik</creatorcontrib><creatorcontrib>Fostira, Florentia</creatorcontrib><creatorcontrib>Gammon, Marilie</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Guénel, Pascal</creatorcontrib><creatorcontrib>Haiman, Christopher A</creatorcontrib><creatorcontrib>Hamann, Ute</creatorcontrib><creatorcontrib>Hooning, Maartje J</creatorcontrib><creatorcontrib>Hopper, John L</creatorcontrib><creatorcontrib>Jakubowska, Anna</creatorcontrib><creatorcontrib>Jasmine, Farzana</creatorcontrib><creatorcontrib>Jenkins, Mark</creatorcontrib><creatorcontrib>John, Esther M</creatorcontrib><creatorcontrib>Johnson, Nichola</creatorcontrib><creatorcontrib>Jones, Michael E</creatorcontrib><creatorcontrib>Kabisch, Maria</creatorcontrib><creatorcontrib>Kibriya, Muhammad</creatorcontrib><creatorcontrib>Knight, Julia A</creatorcontrib><creatorcontrib>Koppert, Linetta B</creatorcontrib><creatorcontrib>Kristensen, Vessela</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Lee, Eunjung</creatorcontrib><creatorcontrib>Li, Jingmei</creatorcontrib><creatorcontrib>Lindblom, Annika</creatorcontrib><creatorcontrib>Luben, Robert</creatorcontrib><creatorcontrib>Malone, Kathi E</creatorcontrib><creatorcontrib>Mannermaa, Arto</creatorcontrib><creatorcontrib>Margolin, Sara</creatorcontrib><creatorcontrib>Marme, Frederik</creatorcontrib><creatorcontrib>McLean, Catriona</creatorcontrib><creatorcontrib>Meijers-Heijboer, Hanne</creatorcontrib><creatorcontrib>Meindl, Alfons</creatorcontrib><creatorcontrib>Neuhausen, Susan L</creatorcontrib><creatorcontrib>Nevanlinna, Heli</creatorcontrib><creatorcontrib>Neven, Patrick</creatorcontrib><creatorcontrib>Perez, Jose I. A</creatorcontrib><creatorcontrib>Perkins, Barbara</creatorcontrib><creatorcontrib>Peterlongo, Paolo</creatorcontrib><creatorcontrib>Phillips, Kelly-Anne</creatorcontrib><creatorcontrib>Pylkäs, Katri</creatorcontrib><creatorcontrib>Rudolph, Anja</creatorcontrib><creatorcontrib>Sawyer, Elinor J</creatorcontrib><creatorcontrib>Schmutzler, Rita K</creatorcontrib><creatorcontrib>Seynaeve, Caroline</creatorcontrib><creatorcontrib>Shah, Mitul</creatorcontrib><creatorcontrib>Shrubsole, Martha J</creatorcontrib><creatorcontrib>Southey, Melissa C</creatorcontrib><creatorcontrib>Swerdlow, Anthony J</creatorcontrib><creatorcontrib>Tomlinson, Ian</creatorcontrib><creatorcontrib>Torres, Diana</creatorcontrib><creatorcontrib>Truong, Thérèse</creatorcontrib><creatorcontrib>Ursin, Giske</creatorcontrib><creatorcontrib>Van Der Luijt, Rob B</creatorcontrib><creatorcontrib>Verhoef, Senno</creatorcontrib><creatorcontrib>Whittemore, Alice S</creatorcontrib><creatorcontrib>Winqvist, Robert</creatorcontrib><creatorcontrib>Zhao, Shilin</creatorcontrib><creatorcontrib>Hall, Per</creatorcontrib><creatorcontrib>Simard, Jacques</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Pharoah, Paul</creatorcontrib><creatorcontrib>Hunter, David</creatorcontrib><creatorcontrib>Zheng, Wei</creatorcontrib><title>Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent</title><title>PLoS Medicine</title><description>Background Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. Methods We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. Results In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m.sup.2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 x 10.sup.-10). The associations were similar for both premenopausal (OR = 0.44, 95% CI:0.31-0.62, p = 9.91 x 10.sup.-8) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46-0.71, p = 1.88 x 10.sup.-8). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60-0.84, p = 1.64 x 10.sup.-7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p < 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. Conclusions BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.</description><subject>Body mass index</subject><subject>Breast cancer</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Postmenopausal women</subject><subject>Risk factors</subject><subject>Single nucleotide polymorphisms</subject><issn>1549-1277</issn><fulltext>true</fulltext><rsrctype>report</rsrctype><creationdate>2016</creationdate><recordtype>report</recordtype><sourceid/><recordid>eNqVjs1KAzEUhbNQsP68gYv7AHZMOjNM4662tbooSBFcyiW5I6mZm5Kk4PgOvrMRfAE5iwPfOQeOENdKVqru1O0-HCOjrw4D2UpJOVOyPRET1TZ6qmZddybOU9oXrqWWE_G9IabsDHo_wnMk60wmC_fBjrDFlOCJLX0CcmGRMGVYIhuKsHPp4w62VGLvkGFXKmFwX5hdYFiUC2OiBKGHFWaEPoYBVNPeSCnhNQzEv9H6GMOBynpFyRDnS3Hao0909ecXonpYvywfp-_o6c1xH3JEU2RpcCYw9a7wRdPpRtXzua7_PfgBtI5ixQ</recordid><startdate>20160823</startdate><enddate>20160823</enddate><creator>Guo, Yan</creator><creator>Warren Andersen, Shaneda</creator><creator>Michailidou, Kyriaki</creator><creator>Bolla, Manjeet K</creator><creator>Wang, Qin</creator><creator>Garcia-Closas, Montserrat</creator><creator>Milne, Roger L</creator><creator>Schmidt, Marjanka K</creator><creator>Chang-Claude, Jenny</creator><creator>Dunning, Allison</creator><creator>Bojesen, Stig E</creator><creator>Ahsan, Habibul</creator><creator>Aittomäki, Kristiina</creator><creator>Andrulis, Irene L</creator><creator>Arndt, Volker</creator><creator>Beckmann, Matthias W</creator><creator>Beeghly-Fadiel, Alicia</creator><creator>Benitez, Javier</creator><creator>Bonanni, Bernardo</creator><creator>Børresen-Dale, Anne-Lise</creator><creator>Brand, Judith</creator><creator>Brauch, Hiltrud</creator><creator>Brenner, Hermann</creator><creator>Brüning, Thomas</creator><creator>Burwinkel, Barbara</creator><creator>Casey, Graham</creator><creator>Chenevix-Trench, Georgia</creator><creator>Cox, Angela</creator><creator>Cross, Simon S</creator><creator>Czene, Kamila</creator><creator>Devilee, Peter</creator><creator>Dörk, Thilo</creator><creator>Dumont, Ma</creator><creator>Fasching, Peter A</creator><creator>Figueroa, Jonine</creator><creator>Flesch-Janys, Dieter</creator><creator>Fletcher, Olivia</creator><creator>Flyger, Henrik</creator><creator>Fostira, Florentia</creator><creator>Gammon, Marilie</creator><creator>Giles, Graham G</creator><creator>Guénel, Pascal</creator><creator>Haiman, Christopher A</creator><creator>Hamann, Ute</creator><creator>Hooning, Maartje J</creator><creator>Hopper, John L</creator><creator>Jakubowska, Anna</creator><creator>Jasmine, Farzana</creator><creator>Jenkins, Mark</creator><creator>John, Esther M</creator><creator>Johnson, Nichola</creator><creator>Jones, Michael E</creator><creator>Kabisch, Maria</creator><creator>Kibriya, Muhammad</creator><creator>Knight, Julia A</creator><creator>Koppert, Linetta B</creator><creator>Kristensen, Vessela</creator><creator>Le Marchand, Loic</creator><creator>Lee, Eunjung</creator><creator>Li, Jingmei</creator><creator>Lindblom, Annika</creator><creator>Luben, Robert</creator><creator>Malone, Kathi E</creator><creator>Mannermaa, Arto</creator><creator>Margolin, Sara</creator><creator>Marme, Frederik</creator><creator>McLean, Catriona</creator><creator>Meijers-Heijboer, Hanne</creator><creator>Meindl, Alfons</creator><creator>Neuhausen, Susan L</creator><creator>Nevanlinna, Heli</creator><creator>Neven, Patrick</creator><creator>Perez, Jose I. A</creator><creator>Perkins, Barbara</creator><creator>Peterlongo, Paolo</creator><creator>Phillips, Kelly-Anne</creator><creator>Pylkäs, Katri</creator><creator>Rudolph, Anja</creator><creator>Sawyer, Elinor J</creator><creator>Schmutzler, Rita K</creator><creator>Seynaeve, Caroline</creator><creator>Shah, Mitul</creator><creator>Shrubsole, Martha J</creator><creator>Southey, Melissa C</creator><creator>Swerdlow, Anthony J</creator><creator>Tomlinson, Ian</creator><creator>Torres, Diana</creator><creator>Truong, Thérèse</creator><creator>Ursin, Giske</creator><creator>Van Der Luijt, Rob B</creator><creator>Verhoef, Senno</creator><creator>Whittemore, Alice S</creator><creator>Winqvist, Robert</creator><creator>Zhao, Shilin</creator><creator>Hall, Per</creator><creator>Simard, Jacques</creator><creator>Kraft, Peter</creator><creator>Pharoah, Paul</creator><creator>Hunter, David</creator><creator>Zheng, Wei</creator><general>Public Library of Science</general><scope/></search><sort><creationdate>20160823</creationdate><title>Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent</title><author>Guo, Yan ; Warren Andersen, Shaneda ; Michailidou, Kyriaki ; Bolla, Manjeet K ; Wang, Qin ; Garcia-Closas, Montserrat ; Milne, Roger L ; Schmidt, Marjanka K ; Chang-Claude, Jenny ; Dunning, Allison ; Bojesen, Stig E ; Ahsan, Habibul ; Aittomäki, Kristiina ; Andrulis, Irene L ; Arndt, Volker ; Beckmann, Matthias W ; Beeghly-Fadiel, Alicia ; Benitez, Javier ; Bonanni, Bernardo ; Børresen-Dale, Anne-Lise ; Brand, Judith ; Brauch, Hiltrud ; Brenner, Hermann ; Brüning, Thomas ; Burwinkel, Barbara ; Casey, Graham ; Chenevix-Trench, Georgia ; Cox, Angela ; Cross, Simon S ; Czene, Kamila ; Devilee, Peter ; Dörk, Thilo ; Dumont, Ma ; Fasching, Peter A ; Figueroa, Jonine ; Flesch-Janys, Dieter ; Fletcher, Olivia ; Flyger, Henrik ; Fostira, Florentia ; Gammon, Marilie ; Giles, Graham G ; Guénel, Pascal ; Haiman, Christopher A ; Hamann, Ute ; Hooning, Maartje J ; Hopper, John L ; Jakubowska, Anna ; Jasmine, Farzana ; Jenkins, Mark ; John, Esther M ; Johnson, Nichola ; Jones, Michael E ; Kabisch, Maria ; Kibriya, Muhammad ; Knight, Julia A ; Koppert, Linetta B ; Kristensen, Vessela ; Le Marchand, Loic ; Lee, Eunjung ; Li, Jingmei ; Lindblom, Annika ; Luben, Robert ; Malone, Kathi E ; Mannermaa, Arto ; Margolin, Sara ; Marme, Frederik ; McLean, Catriona ; Meijers-Heijboer, Hanne ; Meindl, Alfons ; Neuhausen, Susan L ; Nevanlinna, Heli ; Neven, Patrick ; Perez, Jose I. A ; Perkins, Barbara ; Peterlongo, Paolo ; Phillips, Kelly-Anne ; Pylkäs, Katri ; Rudolph, Anja ; Sawyer, Elinor J ; Schmutzler, Rita K ; Seynaeve, Caroline ; Shah, Mitul ; Shrubsole, Martha J ; Southey, Melissa C ; Swerdlow, Anthony J ; Tomlinson, Ian ; Torres, Diana ; Truong, Thérèse ; Ursin, Giske ; Van Der Luijt, Rob B ; Verhoef, Senno ; Whittemore, Alice S ; Winqvist, Robert ; Zhao, Shilin ; Hall, Per ; Simard, Jacques ; Kraft, Peter ; Pharoah, Paul ; Hunter, David ; Zheng, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-gale_infotracacademiconefile_A4794138893</frbrgroupid><rsrctype>reports</rsrctype><prefilter>reports</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Body mass index</topic><topic>Breast cancer</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Postmenopausal women</topic><topic>Risk factors</topic><topic>Single nucleotide polymorphisms</topic><toplevel>online_resources</toplevel><creatorcontrib>Guo, Yan</creatorcontrib><creatorcontrib>Warren Andersen, Shaneda</creatorcontrib><creatorcontrib>Michailidou, Kyriaki</creatorcontrib><creatorcontrib>Bolla, Manjeet K</creatorcontrib><creatorcontrib>Wang, Qin</creatorcontrib><creatorcontrib>Garcia-Closas, Montserrat</creatorcontrib><creatorcontrib>Milne, Roger L</creatorcontrib><creatorcontrib>Schmidt, Marjanka K</creatorcontrib><creatorcontrib>Chang-Claude, Jenny</creatorcontrib><creatorcontrib>Dunning, Allison</creatorcontrib><creatorcontrib>Bojesen, Stig E</creatorcontrib><creatorcontrib>Ahsan, Habibul</creatorcontrib><creatorcontrib>Aittomäki, Kristiina</creatorcontrib><creatorcontrib>Andrulis, Irene L</creatorcontrib><creatorcontrib>Arndt, Volker</creatorcontrib><creatorcontrib>Beckmann, Matthias W</creatorcontrib><creatorcontrib>Beeghly-Fadiel, Alicia</creatorcontrib><creatorcontrib>Benitez, Javier</creatorcontrib><creatorcontrib>Bonanni, Bernardo</creatorcontrib><creatorcontrib>Børresen-Dale, Anne-Lise</creatorcontrib><creatorcontrib>Brand, Judith</creatorcontrib><creatorcontrib>Brauch, Hiltrud</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Brüning, Thomas</creatorcontrib><creatorcontrib>Burwinkel, Barbara</creatorcontrib><creatorcontrib>Casey, Graham</creatorcontrib><creatorcontrib>Chenevix-Trench, Georgia</creatorcontrib><creatorcontrib>Cox, Angela</creatorcontrib><creatorcontrib>Cross, Simon S</creatorcontrib><creatorcontrib>Czene, Kamila</creatorcontrib><creatorcontrib>Devilee, Peter</creatorcontrib><creatorcontrib>Dörk, Thilo</creatorcontrib><creatorcontrib>Dumont, Ma</creatorcontrib><creatorcontrib>Fasching, Peter A</creatorcontrib><creatorcontrib>Figueroa, Jonine</creatorcontrib><creatorcontrib>Flesch-Janys, Dieter</creatorcontrib><creatorcontrib>Fletcher, Olivia</creatorcontrib><creatorcontrib>Flyger, Henrik</creatorcontrib><creatorcontrib>Fostira, Florentia</creatorcontrib><creatorcontrib>Gammon, Marilie</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Guénel, Pascal</creatorcontrib><creatorcontrib>Haiman, Christopher A</creatorcontrib><creatorcontrib>Hamann, Ute</creatorcontrib><creatorcontrib>Hooning, Maartje J</creatorcontrib><creatorcontrib>Hopper, John L</creatorcontrib><creatorcontrib>Jakubowska, Anna</creatorcontrib><creatorcontrib>Jasmine, Farzana</creatorcontrib><creatorcontrib>Jenkins, Mark</creatorcontrib><creatorcontrib>John, Esther M</creatorcontrib><creatorcontrib>Johnson, Nichola</creatorcontrib><creatorcontrib>Jones, Michael E</creatorcontrib><creatorcontrib>Kabisch, Maria</creatorcontrib><creatorcontrib>Kibriya, Muhammad</creatorcontrib><creatorcontrib>Knight, Julia A</creatorcontrib><creatorcontrib>Koppert, Linetta B</creatorcontrib><creatorcontrib>Kristensen, Vessela</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Lee, Eunjung</creatorcontrib><creatorcontrib>Li, Jingmei</creatorcontrib><creatorcontrib>Lindblom, Annika</creatorcontrib><creatorcontrib>Luben, Robert</creatorcontrib><creatorcontrib>Malone, Kathi E</creatorcontrib><creatorcontrib>Mannermaa, Arto</creatorcontrib><creatorcontrib>Margolin, Sara</creatorcontrib><creatorcontrib>Marme, Frederik</creatorcontrib><creatorcontrib>McLean, Catriona</creatorcontrib><creatorcontrib>Meijers-Heijboer, Hanne</creatorcontrib><creatorcontrib>Meindl, Alfons</creatorcontrib><creatorcontrib>Neuhausen, Susan L</creatorcontrib><creatorcontrib>Nevanlinna, Heli</creatorcontrib><creatorcontrib>Neven, Patrick</creatorcontrib><creatorcontrib>Perez, Jose I. A</creatorcontrib><creatorcontrib>Perkins, Barbara</creatorcontrib><creatorcontrib>Peterlongo, Paolo</creatorcontrib><creatorcontrib>Phillips, Kelly-Anne</creatorcontrib><creatorcontrib>Pylkäs, Katri</creatorcontrib><creatorcontrib>Rudolph, Anja</creatorcontrib><creatorcontrib>Sawyer, Elinor J</creatorcontrib><creatorcontrib>Schmutzler, Rita K</creatorcontrib><creatorcontrib>Seynaeve, Caroline</creatorcontrib><creatorcontrib>Shah, Mitul</creatorcontrib><creatorcontrib>Shrubsole, Martha J</creatorcontrib><creatorcontrib>Southey, Melissa C</creatorcontrib><creatorcontrib>Swerdlow, Anthony J</creatorcontrib><creatorcontrib>Tomlinson, Ian</creatorcontrib><creatorcontrib>Torres, Diana</creatorcontrib><creatorcontrib>Truong, Thérèse</creatorcontrib><creatorcontrib>Ursin, Giske</creatorcontrib><creatorcontrib>Van Der Luijt, Rob B</creatorcontrib><creatorcontrib>Verhoef, Senno</creatorcontrib><creatorcontrib>Whittemore, Alice S</creatorcontrib><creatorcontrib>Winqvist, Robert</creatorcontrib><creatorcontrib>Zhao, Shilin</creatorcontrib><creatorcontrib>Hall, Per</creatorcontrib><creatorcontrib>Simard, Jacques</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Pharoah, Paul</creatorcontrib><creatorcontrib>Hunter, David</creatorcontrib><creatorcontrib>Zheng, Wei</creatorcontrib></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Yan</au><au>Warren Andersen, Shaneda</au><au>Michailidou, Kyriaki</au><au>Bolla, Manjeet K</au><au>Wang, Qin</au><au>Garcia-Closas, Montserrat</au><au>Milne, Roger L</au><au>Schmidt, Marjanka K</au><au>Chang-Claude, Jenny</au><au>Dunning, Allison</au><au>Bojesen, Stig E</au><au>Ahsan, Habibul</au><au>Aittomäki, Kristiina</au><au>Andrulis, Irene L</au><au>Arndt, Volker</au><au>Beckmann, Matthias W</au><au>Beeghly-Fadiel, Alicia</au><au>Benitez, Javier</au><au>Bonanni, Bernardo</au><au>Børresen-Dale, Anne-Lise</au><au>Brand, Judith</au><au>Brauch, Hiltrud</au><au>Brenner, Hermann</au><au>Brüning, Thomas</au><au>Burwinkel, Barbara</au><au>Casey, Graham</au><au>Chenevix-Trench, Georgia</au><au>Cox, Angela</au><au>Cross, Simon S</au><au>Czene, Kamila</au><au>Devilee, Peter</au><au>Dörk, Thilo</au><au>Dumont, Ma</au><au>Fasching, Peter A</au><au>Figueroa, Jonine</au><au>Flesch-Janys, Dieter</au><au>Fletcher, Olivia</au><au>Flyger, Henrik</au><au>Fostira, Florentia</au><au>Gammon, Marilie</au><au>Giles, Graham G</au><au>Guénel, Pascal</au><au>Haiman, Christopher A</au><au>Hamann, Ute</au><au>Hooning, Maartje J</au><au>Hopper, John L</au><au>Jakubowska, Anna</au><au>Jasmine, Farzana</au><au>Jenkins, Mark</au><au>John, Esther M</au><au>Johnson, Nichola</au><au>Jones, Michael E</au><au>Kabisch, Maria</au><au>Kibriya, Muhammad</au><au>Knight, Julia A</au><au>Koppert, Linetta B</au><au>Kristensen, Vessela</au><au>Le Marchand, Loic</au><au>Lee, Eunjung</au><au>Li, Jingmei</au><au>Lindblom, Annika</au><au>Luben, Robert</au><au>Malone, Kathi E</au><au>Mannermaa, Arto</au><au>Margolin, Sara</au><au>Marme, Frederik</au><au>McLean, Catriona</au><au>Meijers-Heijboer, Hanne</au><au>Meindl, Alfons</au><au>Neuhausen, Susan L</au><au>Nevanlinna, Heli</au><au>Neven, Patrick</au><au>Perez, Jose I. A</au><au>Perkins, Barbara</au><au>Peterlongo, Paolo</au><au>Phillips, Kelly-Anne</au><au>Pylkäs, Katri</au><au>Rudolph, Anja</au><au>Sawyer, Elinor J</au><au>Schmutzler, Rita K</au><au>Seynaeve, Caroline</au><au>Shah, Mitul</au><au>Shrubsole, Martha J</au><au>Southey, Melissa C</au><au>Swerdlow, Anthony J</au><au>Tomlinson, Ian</au><au>Torres, Diana</au><au>Truong, Thérèse</au><au>Ursin, Giske</au><au>Van Der Luijt, Rob B</au><au>Verhoef, Senno</au><au>Whittemore, Alice S</au><au>Winqvist, Robert</au><au>Zhao, Shilin</au><au>Hall, Per</au><au>Simard, Jacques</au><au>Kraft, Peter</au><au>Pharoah, Paul</au><au>Hunter, David</au><au>Zheng, Wei</au><format>book</format><genre>unknown</genre><ristype>RPRT</ristype><atitle>Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent</atitle><jtitle>PLoS Medicine</jtitle><date>2016-08-23</date><risdate>2016</risdate><volume>13</volume><issue>8</issue><issn>1549-1277</issn><abstract>Background Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. Methods We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. Results In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m.sup.2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 x 10.sup.-10). The associations were similar for both premenopausal (OR = 0.44, 95% CI:0.31-0.62, p = 9.91 x 10.sup.-8) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46-0.71, p = 1.88 x 10.sup.-8). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60-0.84, p = 1.64 x 10.sup.-7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p < 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. Conclusions BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pmed.1002105</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1549-1277 |
| ispartof | PLoS Medicine, 2016, Vol.13 (8) |
| issn | 1549-1277 |
| language | eng |
| recordid | cdi_gale_infotracacademiconefile_A479413889 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Public Library of Science (PLoS) |
| subjects | Body mass index Breast cancer Genetic aspects Health aspects Postmenopausal women Risk factors Single nucleotide polymorphisms |
| title | Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T17%3A54%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=unknown&rft.atitle=Genetically%20Predicted%20Body%20Mass%20Index%20and%20Breast%20Cancer%20Risk:%20Mendelian%20Randomization%20Analyses%20of%20Data%20from%20145,000%20Women%20of%20European%20Descent&rft.jtitle=PLoS%20Medicine&rft.au=Guo,%20Yan&rft.date=2016-08-23&rft.volume=13&rft.issue=8&rft.issn=1549-1277&rft_id=info:doi/10.1371/journal.pmed.1002105&rft_dat=%3Cgale%3EA479413889%3C/gale%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rft_galeid=A479413889&rfr_iscdi=true |