Mendelian randomisation study of smoking exposure in relation to breast cancer risk

NBCS Collaborators; Paul Cohen

doi:10.1038/s41416-021-01432-8

Mendelian randomisation study of smoking exposure in relation to breast cancer risk

NBCS Collaborators, Paul Cohen

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

BACKGROUND: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.

METHODS: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.

RESULTS: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.

CONCLUSION: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

Original language	English
Pages (from-to)	1135-1145
Number of pages	11
Journal	British Journal of Cancer
Volume	125
Issue number	8
DOIs	https://doi.org/10.1038/s41416-021-01432-8
Publication status	Published - 12 Oct 2021
Externally published	Yes

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@article{cfd519459fdb4c4fa2d1b93e2dc71a86,

title = "Mendelian randomisation study of smoking exposure in relation to breast cancer risk",

abstract = "BACKGROUND: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.METHODS: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.RESULTS: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.CONCLUSION: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.",

author = "{NBCS Collaborators} and Park, {Hanla A} and Sonja Neumeyer and Kyriaki Michailidou and Bolla, {Manjeet K} and Qin Wang and Joe Dennis and Ahearn, {Thomas U} and Andrulis, {Irene L} and Hoda Anton-Culver and Antonenkova, {Natalia N} and Volker Arndt and Aronson, {Kristan J} and Annelie Augustinsson and Adinda Baten and {Beane Freeman}, {Laura E} and Heiko Becher and Beckmann, {Matthias W} and Sabine Behrens and Javier Benitez and Marina Bermisheva and Bogdanova, {Natalia V} and Bojesen, {Stig E} and Hiltrud Brauch and Hermann Brenner and Brucker, {Sara Y} and Barbara Burwinkel and Daniele Campa and Federico Canzian and Castelao, {Jose E} and Chanock, {Stephen J} and Georgia Chenevix-Trench and Clarke, {Christine L} and Conroy, {Don M} and Couch, {Fergus J} and Angela Cox and Cross, {Simon S} and Kamila Czene and Daly, {Mary B} and Peter Devilee and Thilo D{\"o}rk and Isabel Dos-Santos-Silva and Miriam Dwek and Eccles, {Diana M} and Eliassen, {A Heather} and Christoph Engel and Mikael Eriksson and Evans, {D Gareth} and Fasching, {Peter A} and Henrik Flyger and Lin Fritschi and Montserrat Garc{\'i}a-Closas and Garc{\'i}a-S{\'a}enz, {Jos{\'e} A} and Gaudet, {Mia M} and Giles, {Graham G} and Gord Glendon and Goldberg, {Mark S} and Goldgar, {David E} and Anna Gonz{\'a}lez-Neira and Mervi Grip and Pascal Gu{\'e}nel and Eric Hahnen and Haiman, {Christopher A} and Niclas H{\aa}kansson and Per Hall and Ute Hamann and Sileny Han and Harkness, {Elaine F} and Hart, {Steven N} and Wei He and Heemskerk-Gerritsen, {Bernadette A M} and Hopper, {John L} and Hunter, {David J} and Agnes Jager and Anna Jakubowska and John, {Esther M} and Audrey Jung and Rudolf Kaaks and Kapoor, {Pooja Middha} and Renske Keeman and Elza Khusnutdinova and Kitahara, {Cari M} and Koppert, {Linetta B} and Stella Koutros and Kristensen, {Vessela N} and Kurian, {Allison W} and James Lacey and Diether Lambrechts and {Le Marchand}, Loic and Wing-Yee Lo and Jan Lubi{\'n}ski and Arto Mannermaa and Mehdi Manoochehri and Sara Margolin and Martinez, {Maria Elena} and Dimitrios Mavroudis and Alfons Meindl and Usha Menon and Milne, {Roger L} and Muranen, {Taru A} and Heli Nevanlinna and Newman, {William G} and Nordestgaard, {B{\o}rge G} and Kenneth Offit and Olshan, {Andrew F} and H{\aa}kan Olsson and Tjoung-Won Park-Simon and Paolo Peterlongo and Julian Peto and Dijana Plaseska-Karanfilska and Nadege Presneau and Paolo Radice and Gad Rennert and Rennert, {Hedy S} and Atocha Romero and Emmanouil Saloustros and Sawyer, {Elinor J} and Schmidt, {Marjanka K} and Schmutzler, {Rita K} and Schoemaker, {Minouk J} and Lukas Schwentner and Christopher Scott and Mitul Shah and Xiao-Ou Shu and Jacques Simard and Ann Smeets and Southey, {Melissa C} and Spinelli, {John J} and Victoria Stevens and Swerdlow, {Anthony J} and Tamimi, {Rulla M} and Tapper, {William J} and Taylor, {Jack A} and Terry, {Mary Beth} and Ian Tomlinson and Troester, {Melissa A} and Th{\'e}r{\`e}se Truong and Vachon, {Celine M} and {van Veen}, {Elke M} and Joseph Vijai and Sophia Wang and Camilla Wendt and Robert Winqvist and Alicja Wolk and Argyrios Ziogas and Dunning, {Alison M} and Pharoah, {Paul D P} and Easton, {Douglas F} and Wei Zheng and Peter Kraft and Jenny Chang-Claude and Paul Cohen",

year = "2021",

month = oct,

day = "12",

doi = "10.1038/s41416-021-01432-8",

language = "English",

volume = "125",

pages = "1135--1145",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "8",

}

TY - JOUR

T1 - Mendelian randomisation study of smoking exposure in relation to breast cancer risk

AU - NBCS Collaborators

AU - Park, Hanla A

AU - Neumeyer, Sonja

AU - Michailidou, Kyriaki

AU - Bolla, Manjeet K

AU - Wang, Qin

AU - Dennis, Joe

AU - Ahearn, Thomas U

AU - Andrulis, Irene L

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N

AU - Arndt, Volker

AU - Aronson, Kristan J

AU - Augustinsson, Annelie

AU - Baten, Adinda

AU - Beane Freeman, Laura E

AU - Becher, Heiko

AU - Beckmann, Matthias W

AU - Behrens, Sabine

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Bogdanova, Natalia V

AU - Bojesen, Stig E

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Brucker, Sara Y

AU - Burwinkel, Barbara

AU - Campa, Daniele

AU - Canzian, Federico

AU - Castelao, Jose E

AU - Chanock, Stephen J

AU - Chenevix-Trench, Georgia

AU - Clarke, Christine L

AU - Conroy, Don M

AU - Couch, Fergus J

AU - Cox, Angela

AU - Cross, Simon S

AU - Czene, Kamila

AU - Daly, Mary B

AU - Devilee, Peter

AU - Dörk, Thilo

AU - Dos-Santos-Silva, Isabel

AU - Dwek, Miriam

AU - Eccles, Diana M

AU - Eliassen, A Heather

AU - Engel, Christoph

AU - Eriksson, Mikael

AU - Evans, D Gareth

AU - Fasching, Peter A

AU - Flyger, Henrik

AU - Fritschi, Lin

AU - García-Closas, Montserrat

AU - García-Sáenz, José A

AU - Gaudet, Mia M

AU - Giles, Graham G

AU - Glendon, Gord

AU - Goldberg, Mark S

AU - Goldgar, David E

AU - González-Neira, Anna

AU - Grip, Mervi

AU - Guénel, Pascal

AU - Hahnen, Eric

AU - Haiman, Christopher A

AU - Håkansson, Niclas

AU - Hall, Per

AU - Hamann, Ute

AU - Han, Sileny

AU - Harkness, Elaine F

AU - Hart, Steven N

AU - He, Wei

AU - Heemskerk-Gerritsen, Bernadette A M

AU - Hopper, John L

AU - Hunter, David J

AU - Jager, Agnes

AU - Jakubowska, Anna

AU - John, Esther M

AU - Jung, Audrey

AU - Kaaks, Rudolf

AU - Kapoor, Pooja Middha

AU - Keeman, Renske

AU - Khusnutdinova, Elza

AU - Kitahara, Cari M

AU - Koppert, Linetta B

AU - Koutros, Stella

AU - Kristensen, Vessela N

AU - Kurian, Allison W

AU - Lacey, James

AU - Lambrechts, Diether

AU - Le Marchand, Loic

AU - Lo, Wing-Yee

AU - Lubiński, Jan

AU - Mannermaa, Arto

AU - Manoochehri, Mehdi

AU - Margolin, Sara

AU - Martinez, Maria Elena

AU - Mavroudis, Dimitrios

AU - Meindl, Alfons

AU - Menon, Usha

AU - Milne, Roger L

AU - Muranen, Taru A

AU - Nevanlinna, Heli

AU - Newman, William G

AU - Nordestgaard, Børge G

AU - Offit, Kenneth

AU - Olshan, Andrew F

AU - Olsson, Håkan

AU - Park-Simon, Tjoung-Won

AU - Peterlongo, Paolo

AU - Peto, Julian

AU - Plaseska-Karanfilska, Dijana

AU - Presneau, Nadege

AU - Radice, Paolo

AU - Rennert, Gad

AU - Rennert, Hedy S

AU - Romero, Atocha

AU - Saloustros, Emmanouil

AU - Sawyer, Elinor J

AU - Schmidt, Marjanka K

AU - Schmutzler, Rita K

AU - Schoemaker, Minouk J

AU - Schwentner, Lukas

AU - Scott, Christopher

AU - Shah, Mitul

AU - Shu, Xiao-Ou

AU - Simard, Jacques

AU - Smeets, Ann

AU - Southey, Melissa C

AU - Spinelli, John J

AU - Stevens, Victoria

AU - Swerdlow, Anthony J

AU - Tamimi, Rulla M

AU - Tapper, William J

AU - Taylor, Jack A

AU - Terry, Mary Beth

AU - Tomlinson, Ian

AU - Troester, Melissa A

AU - Truong, Thérèse

AU - Vachon, Celine M

AU - van Veen, Elke M

AU - Vijai, Joseph

AU - Wang, Sophia

AU - Wendt, Camilla

AU - Winqvist, Robert

AU - Wolk, Alicja

AU - Ziogas, Argyrios

AU - Dunning, Alison M

AU - Pharoah, Paul D P

AU - Easton, Douglas F

AU - Zheng, Wei

AU - Kraft, Peter

AU - Chang-Claude, Jenny

AU - Cohen, Paul

PY - 2021/10/12

Y1 - 2021/10/12

N2 - BACKGROUND: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.METHODS: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.RESULTS: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.CONCLUSION: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

AB - BACKGROUND: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.METHODS: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.RESULTS: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.CONCLUSION: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

UR - http://www.scopus.com/inward/record.url?scp= 85112658433&partnerID=8YFLogxK

U2 - 10.1038/s41416-021-01432-8

DO - 10.1038/s41416-021-01432-8

M3 - Article

C2 - 34341517

SN - 0007-0920

VL - 125

SP - 1135

EP - 1145

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 8

ER -

Mendelian randomisation study of smoking exposure in relation to breast cancer risk

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