Multi-Trait Body Shape Phenotypes and Breast Cancer Risk in Postmenopausal Women: A Causal Mediation Analysis in the UK Biobank Cohort.
Anthropometry
Biomarker
Body shape
Breast cancer
Interaction
Mediation
Journal
Journal of epidemiology and global health
ISSN: 2210-6014
Titre abrégé: J Epidemiol Glob Health
Pays: Switzerland
ID NLM: 101592084
Informations de publication
Date de publication:
10 Apr 2024
10 Apr 2024
Historique:
received:
10
01
2024
accepted:
01
04
2024
medline:
10
4
2024
pubmed:
10
4
2024
entrez:
10
4
2024
Statut:
aheadofprint
Résumé
Body shape phenotypes combining multiple anthropometric traits have been linked to postmenopausal breast cancer (BC). However, underlying biological pathways remain poorly understood. This study investigated to what extent the associations of body shapes with postmenopausal BC risk is mediated by biochemical markers. The study included 176,686 postmenopausal women from UK Biobank. Four body shape phenotypes were derived from principal component (PC) analysis of height, weight, body mass index, waist and hip circumferences, and waist-to-hip ratio (WHR). The four-way decomposition of the total effect was used to estimate mediation and interaction effects simultaneously as well as the mediated proportions. After 10.9 years median follow-up, 6,396 incident postmenopausal BC were diagnosed. There was strong evidence of positive associations between PC1 (general obesity) and PC2 (tall, low WHR), and BC risk. The association of PC1 with BC risk was positively mediated by testosterone and negatively by insulin-like growth factor-1 (IGF-1), with the overall proportion mediated (sum of the mediated interaction and pure indirect effect (PIE)) accounting for 11.4% (95% confidence intervals: 5.1 to 17.8%) and -12.2% (-20.5% to -4.0%) of the total effect, respectively. Small proportions of the association between PC2 and BC were mediated by IGF-1 (PIE: 2.8% (0.6 to 4.9%)), and sex hormone-binding globulin (SHBG) (PIE: -6.1% (-10.9% to -1.3%)). Our findings are consistent with differential pathways linking different body shapes with BC risk, with a suggestive mediation through testosterone and IGF-1 in the relationship of a generally obese body shape and BC risk, while IGF-1 and SHBG may mediate a tall/lean body shape-BC risk association.
Identifiants
pubmed: 38598163
doi: 10.1007/s44197-024-00226-4
pii: 10.1007/s44197-024-00226-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Institut National Du Cancer
ID : INCA_14108
Informations de copyright
© 2024. The Author(s).
Références
Argolo DF, Hudis CA, Iyengar NM. The impact of obesity on breast Cancer. Curr Oncol Rep. 2018;20:47. https://doi.org/10.1007/s11912-018-0688-8 .
doi: 10.1007/s11912-018-0688-8
pubmed: 29644507
Lee K, Kruper L, Dieli-Conwright CM, Mortimer JE. The impact of obesity on breast Cancer diagnosis and treatment. Curr Oncol Rep. 2019;21:41. https://doi.org/10.1007/s11912-019-0787-1 .
doi: 10.1007/s11912-019-0787-1
pubmed: 30919143
pmcid: 6437123
Freisling H, Arnold M, Soerjomataram I, O’Doherty MG, Ordonez-Mena JM, Bamia C, et al. Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe. Br J Cancer. 2017;116:1486–97. https://doi.org/10.1038/bjc.2017.106 .
doi: 10.1038/bjc.2017.106
pubmed: 28441380
pmcid: 5520086
Amadou A, Hainaut P, Romieu I. Role of obesity in the risk of breast cancer: lessons from anthropometry. J Oncol. 2013;2013:906495. https://doi.org/10.1155/2013/906495 .
doi: 10.1155/2013/906495
pubmed: 23431300
pmcid: 3575614
Engin A. Obesity-associated breast Cancer: analysis of risk factors. Adv Exp Med Biol. 2017;960:571–606. https://doi.org/10.1007/978-3-319-48382-5_25 .
doi: 10.1007/978-3-319-48382-5_25
pubmed: 28585217
Fortner RT, Katzke V, Kühn T, Kaaks R. Obesity and breast Cancer. Recent Results Cancer Res. 2016;208:43–65. https://doi.org/10.1007/978-3-319-42542-9_3 .
doi: 10.1007/978-3-319-42542-9_3
pubmed: 27909901
Yung RL, Ligibel JA. Obesity and breast cancer: risk, outcomes, and future considerations. Clin Adv Hematol Oncol. 2016;14:790–7.
pubmed: 27930630
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA: A Cancer. J Clin. 2021;71:209–49. https://doi.org/10.3322/caac.21660 .
doi: 10.3322/caac.21660
Al-Ajmi K, Lophatananon A, Ollier W, Muir KR. Risk of breast cancer in the UK biobank female cohort and its relationship to anthropometric and reproductive factors. PLoS ONE. 2018;13:e0201097. https://doi.org/10.1371/journal.pone.0201097 .
doi: 10.1371/journal.pone.0201097
pubmed: 30048498
pmcid: 6062099
Sedlmeier A, Viallon V, Ferrari P, Peruchet-Noray L, Fontvieille E, Amadou A, et al. Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study. Br J Cancer. 2022. https://doi.org/10.1038/s41416-022-02071-3 .
doi: 10.1038/s41416-022-02071-3
pubmed: 36460776
pmcid: 9938222
Ried JS, Jeff JM, Chu AY, Bragg-Gresham JL, van Dongen J, Huffman JE, et al. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape. Nat Commun. 2016;7:1–11. https://doi.org/10.1038/ncomms13357 .
doi: 10.1038/ncomms13357
Brown KA. Metabolic pathways in obesity-related breast cancer. Nat Rev Endocrinol. 2021;17:350–63. https://doi.org/10.1038/s41574-021-00487-0 .
doi: 10.1038/s41574-021-00487-0
pubmed: 33927368
pmcid: 10410950
Devericks EN, Carson MS, McCullough LE, Coleman MF, Hursting SD. The obesity-breast cancer link: a multidisciplinary perspective. Cancer Metastasis Rev. 2022;41:607–25. https://doi.org/10.1007/s10555-022-10043-5 .
doi: 10.1007/s10555-022-10043-5
pubmed: 35752704
pmcid: 9470704
Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. Obesity and Cancer mechanisms: Tumor Microenvironment and inflammation. J Clin Oncol. 2016;34:4270–6. https://doi.org/10.1200/JCO.2016.67.4283 .
doi: 10.1200/JCO.2016.67.4283
pubmed: 27903155
pmcid: 5562428
Watts EL, Perez-Cornago A, Knuppel A, Tsilidis KK, Key TJ, Travis RC. Prospective analyses of testosterone and sex hormone-binding globulin with the risk of 19 types of cancer in men and postmenopausal women in UK Biobank. Int J Cancer. 2021;149:573–84. https://doi.org/10.1002/ijc.33555 .
doi: 10.1002/ijc.33555
pubmed: 33720423
Tin Tin S, Key TJ, Reeves GK. Alcohol intake and endogenous hormones in pre- and Postmenopausal women: findings from the UK Biobank. Cancer Epidemiol Biomarkers Prev. 2021;30:2294–301. https://doi.org/10.1158/1055-9965.EPI-21-0789 .
doi: 10.1158/1055-9965.EPI-21-0789
pubmed: 34607837
pmcid: 9398104
Arthur RS, Dannenberg AJ, Rohan TE. The association of prediagnostic circulating levels of cardiometabolic markers, testosterone and sex hormone-binding globulin with risk of breast cancer among normal weight postmenopausal women in the UK Biobank. Int J Cancer. 2021;149:42–57. https://doi.org/10.1002/ijc.33508 .
doi: 10.1002/ijc.33508
pubmed: 33567105
Guo W, Fensom GK, Reeves GK, Key TJ. Physical activity and breast cancer risk: results from the UK Biobank prospective cohort. Br J Cancer. 2020;122:726–32. https://doi.org/10.1038/s41416-019-0700-6 .
doi: 10.1038/s41416-019-0700-6
pubmed: 31919405
pmcid: 7054300
Menopause. NhsUk. 2017. https://www.nhs.uk/conditions/menopause/ (accessed February 1, 2023).
Conroy MC, Lacey B, Bešević J, Omiyale W, Feng Q, Effingham M et al. UK Biobank: a globally important resource for cancer research. Br J Cancer 2022:1–9. https://doi.org/10.1038/s41416-022-02053-5 .
Christakoudi S, Tsilidis KK, Evangelou E, Riboli E. A body shape index (ABSI), hip index, and risk of cancer in the UK Biobank cohort. Cancer Med. 2021;10:5614–28. https://doi.org/10.1002/cam4.4097 .
doi: 10.1002/cam4.4097
pubmed: 34196490
pmcid: 8366087
Category 17518 n.d. https://biobank.ndph.ox.ac.uk/ukb/label.cgi?id=17518 (accessed April 3, 2023).
Patterson RE, Rock CL, Kerr J, Natarajan L, Marshall SJ, Pakiz B, et al. Metabolism and breast cancer risk: frontiers in research and practice. J Acad Nutr Diet. 2013;113:288–96. https://doi.org/10.1016/j.jand.2012.08.015 .
doi: 10.1016/j.jand.2012.08.015
pubmed: 23127511
Durrleman S, Simon R. Flexible regression models with cubic splines. Stat Med. 1989;8:551–61.
doi: 10.1002/sim.4780080504
pubmed: 2657958
Harrell F. Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. Regression modeling strategies. New York: Springer; 2001.
doi: 10.1007/978-1-4757-3462-1
Discacciati A, Bellavia A, Lee JJ, Mazumdar M, Valeri L. Med4way: a Stata command to investigate mediating and interactive mechanisms using the four-way effect decomposition. Int J Epidemiol. 2018. https://doi.org/10.1093/ije/dyy236 .
doi: 10.1093/ije/dyy236
pubmed: 30452641
VanderWeele TJ. A unification of mediation and interaction: a 4-way decomposition. Epidemiology. 2014;25:749–61. https://doi.org/10.1097/EDE.0000000000000121 .
doi: 10.1097/EDE.0000000000000121
pubmed: 25000145
pmcid: 4220271
Hepsomali P, Groeger JA. Diet, Sleep, and Mental Health: insights from the UK Biobank Study. Nutrients. 2021;13:2573. https://doi.org/10.3390/nu13082573 .
doi: 10.3390/nu13082573
pubmed: 34444731
pmcid: 8398967
Sterne JAC, White IR, Carlin JB, Spratt M, Royston P, Kenward MG, et al. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ. 2009;338:b2393. https://doi.org/10.1136/bmj.b2393 .
doi: 10.1136/bmj.b2393
pubmed: 19564179
pmcid: 2714692
Peruchet-Noray L, Sedlmeier AM, Dimou N, Baurecht H, Fervers B, Fontvieille E et al. Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer. Sci Adv, 2024, in Press n.d.
Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer. 2015;15:484–98. https://doi.org/10.1038/nrc3967 .
doi: 10.1038/nrc3967
pubmed: 26205341
Nimptsch K, Pischon T. Obesity biomarkers, metabolism and risk of Cancer: an epidemiological perspective. Recent Results Cancer Res. 2016;208:199–217. https://doi.org/10.1007/978-3-319-42542-9_11 .
doi: 10.1007/978-3-319-42542-9_11
pubmed: 27909909
Murphy N, Knuppel A, Papadimitriou N, Martin RM, Tsilidis KK, Smith-Byrne K, et al. Insulin-like growth factor-1, insulin-like growth factor-binding protein-3, and breast cancer risk: observational and mendelian randomization analyses with ∼430 000 women. Ann Oncol. 2020;31:641–9. https://doi.org/10.1016/j.annonc.2020.01.066 .
doi: 10.1016/j.annonc.2020.01.066
pubmed: 32169310
Christopoulos PF, Msaouel P, Koutsilieris M. The role of the insulin-like growth factor-1 system in breast cancer. Mol Cancer. 2015;14:43. https://doi.org/10.1186/s12943-015-0291-7 .
doi: 10.1186/s12943-015-0291-7
pubmed: 25743390
pmcid: 4335664
Stefan N, Häring H-U, Hu FB, Schulze MB. Divergent associations of height with cardiometabolic disease and cancer: epidemiology, pathophysiology, and global implications. Lancet Diabetes Endocrinol. 2016;4:457–67. https://doi.org/10.1016/S2213-8587(15)00474-X .
doi: 10.1016/S2213-8587(15)00474-X
pubmed: 26827112
He XY, Liao YD, Yu S, Zhang Y, Wang R. Sex hormone binding globulin and risk of breast cancer in postmenopausal women: a meta-analysis of prospective studies. Horm Metab Res. 2015;47:485–90. https://doi.org/10.1055/s-0034-1395606 .
doi: 10.1055/s-0034-1395606
pubmed: 25565095
Hazelwood E, Sanderson E, Tan VY, Ruth KS, Frayling TM, Dimou N, et al. Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: a mendelian randomization analysis. BMC Med. 2022;20:125. https://doi.org/10.1186/s12916-022-02322-3 .
doi: 10.1186/s12916-022-02322-3
pubmed: 35436960
pmcid: 9017004
Assi N, Rinaldi S, Viallon V, Dashti SG, Dossus L, Fournier A, et al. Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort. Int J Cancer. 2020;146:759–68. https://doi.org/10.1002/ijc.32324 .
doi: 10.1002/ijc.32324
pubmed: 30968961
Bellavia A, Valeri L. Decomposition of the total effect in the Presence of multiple mediators and interactions. Am J Epidemiol. 2018;187:1311–8. https://doi.org/10.1093/aje/kwx355 .
doi: 10.1093/aje/kwx355
pubmed: 29140421