Dataset Information

A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.

ABSTRACT:

Background

Genome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer.

Methods

Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs.

Results

Assuming a 1 × 10^-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (OR_int = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (OR_int = 0.91, 95% CI 0.88-0.94).

Conclusions

Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer.

SUBMITTER: Middha P

PROVIDER: S-EPMC10411002 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.

Middha Pooja P Wang Xiaoliang X Behrens Sabine S Bolla Manjeet K MK Wang Qin Q Dennis Joe J Michailidou Kyriaki K Ahearn Thomas U TU Andrulis Irene L IL Anton-Culver Hoda H Arndt Volker V Aronson Kristan J KJ Auer Paul L PL Augustinsson Annelie A Baert Thaïs T Freeman Laura E Beane LEB Becher Heiko H Beckmann Matthias W MW Benitez Javier J Bojesen Stig E SE Brauch Hiltrud H Brenner Hermann H Brooks-Wilson Angela A Campa Daniele D Canzian Federico F Carracedo Angel A Castelao Jose E JE Chanock Stephen J SJ Chenevix-Trench Georgia G Cordina-Duverger Emilie E Couch Fergus J FJ Cox Angela A Cross Simon S SS Czene Kamila K Dossus Laure L Dugué Pierre-Antoine PA Eliassen A Heather AH Eriksson Mikael M Evans D Gareth DG Fasching Peter A PA Figueroa Jonine D JD Fletcher Olivia O Flyger Henrik H Gabrielson Marike M Gago-Dominguez Manuela M Giles Graham G GG González-Neira Anna A Grassmann Felix F Grundy Anne A Guénel Pascal P Haiman Christopher A CA Håkansson Niclas N Hall Per P Hamann Ute U Hankinson Susan E SE Harkness Elaine F EF Holleczek Bernd B Hoppe Reiner R Hopper John L JL Houlston Richard S RS Howell Anthony A Howell Anthony A Hunter David J DJ Ingvar Christian C Isaksson Karolin K Jernström Helena H John Esther M EM Jones Michael E ME Kaaks Rudolf R Keeman Renske R Kitahara Cari M CM Ko Yon-Dschun YD Koutros Stella S Kurian Allison W AW Lacey James V JV Lambrechts Diether D Larson Nicole L NL Larsson Susanna S Le Marchand Loic L Lejbkowicz Flavio F Li Shuai S Linet Martha M Lissowska Jolanta J Martinez Maria Elena ME Maurer Tabea T Mulligan Anna Marie AM Mulot Claire C Murphy Rachel A RA Newman William G WG Nielsen Sune F SF Nordestgaard Børge G BG Norman Aaron A O'Brien Katie M KM Olson Janet E JE Patel Alpa V AV Prentice Ross R Rees-Punia Erika E Rennert Gad G Rhenius Valerie V Ruddy Kathryn J KJ Sandler Dale P DP Scott Christopher G CG Shah Mitul M Shu Xiao-Ou XO Smeets Ann A Southey Melissa C MC Stone Jennifer J Tamimi Rulla M RM Taylor Jack A JA Teras Lauren R LR Tomczyk Katarzyna K Troester Melissa A MA Truong Thérèse T Vachon Celine M CM Wang Sophia S SS Weinberg Clarice R CR Wildiers Hans H Willett Walter W Winham Stacey J SJ Wolk Alicja A Yang Xiaohong R XR Zamora M Pilar MP Zheng Wei W Ziogas Argyrios A Dunning Alison M AM Pharoah Paul D P PDP García-Closas Montserrat M Schmidt Marjanka K MK Kraft Peter P Milne Roger L RL Lindström Sara S Easton Douglas F DF Chang-Claude Jenny J

Breast cancer research : BCR 20230809 1

<h4>Background</h4>Genome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer.<h4>Methods</h4>Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ance ...[more]

PMID: 37559094

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Project description:Obesity-insulin connections have been considered potential risk factors for postmenopausal breast cancer, and the association between insulin resistance (IR) genotypes and phenotypes can be modified by obesity-lifestyle factors, affecting breast cancer risk. In this study, we explored the role of IR in those pathways at the genome-wide level. We identified IR-genetic factors and selected lifestyles to generate risk profiles for postmenopausal breast cancer. Using large-scale cohort data from postmenopausal women in the Women's Health Initiative Database for Genotypes and Phenotypes Study, our previous genome-wide association gene-behavior interaction study identified 58 loci for associations with IR phenotypes (homeostatic model assessment-IR, hyperglycemia, and hyperinsulinemia). We evaluated those single-nucleotide polymorphisms (SNP) and additional 31 lifestyles in relation to breast cancer risk by conducting a two-stage multimodal random survival forest analysis. We identified the most predictive genetic and lifestyle variables in overall and subgroup analyses [stratified by body mass index (BMI), exercise, and dietary fat intake]. Two SNPs (LINC00460 rs17254590 and MKLN1 rs117911989), exogenous factors related to lifetime cumulative exposure to estrogen, BMI, and dietary alcohol consumption were the most common influential factors across the analyses. Individual SNPs did not have significant associations with breast cancer, but SNPs and lifestyles combined synergistically increased the risk of breast cancer in a gene-behavior, dose-dependent manner. These findings may contribute to more accurate predictions of breast cancer and suggest potential intervention strategies for women with specific genetic and lifestyle factors to reduce their breast cancer risk. SIGNIFICANCE: These findings identify insulin resistance SNPs in combination with lifestyle as synergistic factors for breast cancer risk, suggesting lifestyle changes can prevent breast cancer in women who carry the risk genotypes.

Dataset Information

A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.

Background

Methods

Results

Conclusions

Publications

A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.

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