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Published in: Breast Cancer Research and Treatment 3/2019

01-08-2019 | Breast Cancer | Epidemiology

Breast cancer risk in relation to plasma metabolites among Hispanic and African American women

Authors: Hua Zhao, Jie Shen, Steven C. Moore, Yuanqing Ye, Xifeng Wu, Francisco J. Esteva, Debasish Tripathy, Wong-Ho Chow

Published in: Breast Cancer Research and Treatment | Issue 3/2019

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Abstract

Purpose

The metabolic etiology of breast cancer has been explored in the past several years using metabolomics. However, most of these studies only included non-Hispanic White individuals.

Methods

To fill this gap, we performed a two-step (discovery and validation) metabolomics profiling in plasma samples from 358 breast cancer patients and 138 healthy controls. All study subjects were either Hispanics or non-Hispanic African Americans.

Results

A panel of 14 identified metabolites significantly differed between breast cancer cases and healthy controls in both the discovery and validation sets. Most of these identified metabolites were lipids. In the pathway analysis, citrate cycle (TCA cycle), arginine and proline metabolism, and linoleic acid metabolism pathways were observed, and they significantly differed between breast cancer cases and healthy controls in both sets. From those 14 metabolites, we selected 9 non-correlated metabolites to generate a metabolic risk score. Increased metabolites risk score was associated with a 1.87- and 1.63-fold increased risk of breast cancer in the discovery and validation sets, respectively (Odds ratio (OR) 1.87, 95% Confidence interval (CI) 1.50, 2.32; OR 1.63, 95% CI 1.36, 1.95).

Conclusions

In summary, our study identified metabolic profiles and pathways that significantly differed between breast cancer cases and healthy controls in Hispanic or non-Hispanic African American women. The results from our study might provide new insights on the metabolic etiology of breast cancer.
Literature
9.
go back to reference Tenori L, Oakman C, Morris PG, Gralka E, Turner N, Cappadona S, Fornier M, Hudis C, Norton L, Luchinat C, Di Leo A (2015) Serum metabolomic profiles evaluated after surgery may identify patients with oestrogen receptor negative early breast cancer at increased risk of disease recurrence. Results from a retrospective study. Mol Oncol 9(1):128–139. https://doi.org/10.1016/j.molonc.2014.07.012 CrossRefPubMed Tenori L, Oakman C, Morris PG, Gralka E, Turner N, Cappadona S, Fornier M, Hudis C, Norton L, Luchinat C, Di Leo A (2015) Serum metabolomic profiles evaluated after surgery may identify patients with oestrogen receptor negative early breast cancer at increased risk of disease recurrence. Results from a retrospective study. Mol Oncol 9(1):128–139. https://​doi.​org/​10.​1016/​j.​molonc.​2014.​07.​012 CrossRefPubMed
10.
go back to reference Oakman C, Tenori L, Claudino WM, Cappadona S, Nepi S, Battaglia A, Bernini P, Zafarana E, Saccenti E, Fornier M, Morris PG, Biganzoli L, Luchinat C, Bertini I, Di Leo A (2011) Identification of a serum-detectable metabolomic fingerprint potentially correlated with the presence of micrometastatic disease in early breast cancer patients at varying risks of disease relapse by traditional prognostic methods. Ann Oncol 22(6):1295–1301. https://doi.org/10.1093/annonc/mdq606 CrossRefPubMed Oakman C, Tenori L, Claudino WM, Cappadona S, Nepi S, Battaglia A, Bernini P, Zafarana E, Saccenti E, Fornier M, Morris PG, Biganzoli L, Luchinat C, Bertini I, Di Leo A (2011) Identification of a serum-detectable metabolomic fingerprint potentially correlated with the presence of micrometastatic disease in early breast cancer patients at varying risks of disease relapse by traditional prognostic methods. Ann Oncol 22(6):1295–1301. https://​doi.​org/​10.​1093/​annonc/​mdq606 CrossRefPubMed
15.
go back to reference Evans AM, DeHaven CD, Barrett T, Mitchell M, Milgram E (2009) Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems. Anal Chem 81(16):6656–6667. https://doi.org/10.1021/ac901536h CrossRefPubMed Evans AM, DeHaven CD, Barrett T, Mitchell M, Milgram E (2009) Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems. Anal Chem 81(16):6656–6667. https://​doi.​org/​10.​1021/​ac901536h CrossRefPubMed
17.
go back to reference Sampson JN, Boca SM, Shu XO, Stolzenberg-Solomon RZ, Matthews CE, Hsing AW, Tan YT, Ji BT, Chow WH, Cai QY, Liu DK, Yang G, Xiang YB, Zheng W, Sinha R, Cross AJ, Moore SC (2013) Metabolomics in epidemiology: sources of variability in metabolite measurements and implications. Cancer Epidem Biomar 22(4):631–640. https://doi.org/10.1158/1055-9965.Epi-12-1109 CrossRef Sampson JN, Boca SM, Shu XO, Stolzenberg-Solomon RZ, Matthews CE, Hsing AW, Tan YT, Ji BT, Chow WH, Cai QY, Liu DK, Yang G, Xiang YB, Zheng W, Sinha R, Cross AJ, Moore SC (2013) Metabolomics in epidemiology: sources of variability in metabolite measurements and implications. Cancer Epidem Biomar 22(4):631–640. https://​doi.​org/​10.​1158/​1055-9965.​Epi-12-1109 CrossRef
19.
go back to reference Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, Bouatra S, Sinelnikov I, Arndt D, Xia J, Liu P, Yallou F, Bjorndahl T, Perez-Pineiro R, Eisner R, Allen F, Neveu V, Greiner R, Scalbert A (2013) HMDB 3.0—the human metabolome database in 2013. Nucleic Acids Res 41(Database issue):D801–D807. https://doi.org/10.1093/nar/gks1065 CrossRefPubMed Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, Bouatra S, Sinelnikov I, Arndt D, Xia J, Liu P, Yallou F, Bjorndahl T, Perez-Pineiro R, Eisner R, Allen F, Neveu V, Greiner R, Scalbert A (2013) HMDB 3.0—the human metabolome database in 2013. Nucleic Acids Res 41(Database issue):D801–D807. https://​doi.​org/​10.​1093/​nar/​gks1065 CrossRefPubMed
23.
go back to reference Rodriguez-Enriquez S, Hernandez-Esquivel L, Marin-Hernandez A, El Hafidi M, Gallardo-Perez JC, Hernandez-Resendiz I, Rodriguez-Zavala JS, Pacheco-Velazquez SC, Moreno-Sanchez R (2015) Mitochondrial free fatty acid beta-oxidation supports oxidative phosphorylation and proliferation in cancer cells. Int J Biochem Cell B 65:209–221. https://doi.org/10.1016/j.biocel.2015.06.010 CrossRef Rodriguez-Enriquez S, Hernandez-Esquivel L, Marin-Hernandez A, El Hafidi M, Gallardo-Perez JC, Hernandez-Resendiz I, Rodriguez-Zavala JS, Pacheco-Velazquez SC, Moreno-Sanchez R (2015) Mitochondrial free fatty acid beta-oxidation supports oxidative phosphorylation and proliferation in cancer cells. Int J Biochem Cell B 65:209–221. https://​doi.​org/​10.​1016/​j.​biocel.​2015.​06.​010 CrossRef
30.
go back to reference Li J, Humphreys K, Heikkinen T, Aittomaki K, Blomqvist C, Pharoah PD, Dunning AM, Ahmed S, Hooning MJ, Martens JW, van den Ouweland AM, Alfredsson L, Palotie A, Peltonen-Palotie L, Irwanto A, Low HQ, Teoh GH, Thalamuthu A, Easton DF, Nevanlinna H, Liu J, Czene K, Hall P (2011) A combined analysis of genome-wide association studies in breast cancer. Breast Cancer Res Treat 126(3):717–727. https://doi.org/10.1007/s10549-010-1172-9 CrossRefPubMed Li J, Humphreys K, Heikkinen T, Aittomaki K, Blomqvist C, Pharoah PD, Dunning AM, Ahmed S, Hooning MJ, Martens JW, van den Ouweland AM, Alfredsson L, Palotie A, Peltonen-Palotie L, Irwanto A, Low HQ, Teoh GH, Thalamuthu A, Easton DF, Nevanlinna H, Liu J, Czene K, Hall P (2011) A combined analysis of genome-wide association studies in breast cancer. Breast Cancer Res Treat 126(3):717–727. https://​doi.​org/​10.​1007/​s10549-010-1172-9 CrossRefPubMed
31.
go back to reference Maddocks ODK, Athineos D, Cheung EC, Lee P, Zhang T, van den Broek NJF, Mackay GM, Labuschagne CF, Gay D, Kruiswijk F, Blagih J, Vincent DF, Campbell KJ, Ceteci F, Sansom OJ, Blyth K, Vousden KH (2017) Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature 544(7650):372–376. https://doi.org/10.1038/nature22056 CrossRefPubMed Maddocks ODK, Athineos D, Cheung EC, Lee P, Zhang T, van den Broek NJF, Mackay GM, Labuschagne CF, Gay D, Kruiswijk F, Blagih J, Vincent DF, Campbell KJ, Ceteci F, Sansom OJ, Blyth K, Vousden KH (2017) Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature 544(7650):372–376. https://​doi.​org/​10.​1038/​nature22056 CrossRefPubMed
32.
go back to reference Heber D, Byerly LO, Chlebowski RT (1985) Metabolic abnormalities in the cancer patient. Cancer 55 (1):225–229CrossRefPubMed Heber D, Byerly LO, Chlebowski RT (1985) Metabolic abnormalities in the cancer patient. Cancer 55 (1):225–229CrossRefPubMed
34.
go back to reference Miyagi Y, Higashiyama M, Gochi A, Akaike M, Ishikawa T, Miura T, Saruki N, Bando E, Kimura H, Imamura F, Moriyama M, Ikeda I, Chiba A, Oshita F, Imaizumi A, Yamamoto H, Miyano H, Horimoto K, Tochikubo O, Mitsushima T, Yamakado M, Okamoto N (2011) Plasma free amino acid profiling of five types of cancer patients and its application for early detection. PLoS ONE 6(9):e24143. https://doi.org/10.1371/journal.pone.0024143 CrossRefPubMedPubMedCentral Miyagi Y, Higashiyama M, Gochi A, Akaike M, Ishikawa T, Miura T, Saruki N, Bando E, Kimura H, Imamura F, Moriyama M, Ikeda I, Chiba A, Oshita F, Imaizumi A, Yamamoto H, Miyano H, Horimoto K, Tochikubo O, Mitsushima T, Yamakado M, Okamoto N (2011) Plasma free amino acid profiling of five types of cancer patients and its application for early detection. PLoS ONE 6(9):e24143. https://​doi.​org/​10.​1371/​journal.​pone.​0024143 CrossRefPubMedPubMedCentral
35.
go back to reference Quevedo-Coli S, Crespi C, Benito E, Palou A, Roca P (1997) Alterations in circulating fatty acids and the compartmentation of selected metabolites in women with breast cancer. Biochem Mol Biol Int 41(1):1–10PubMed Quevedo-Coli S, Crespi C, Benito E, Palou A, Roca P (1997) Alterations in circulating fatty acids and the compartmentation of selected metabolites in women with breast cancer. Biochem Mol Biol Int 41(1):1–10PubMed
40.
go back to reference Wen CP, Zhang FM, Liang D, Wen C, Gu J, Skinner H, Chow WH, Ye YQ, Pu X, Hildebrandt MAT, Huang MS, Chen CH, Hsiung CA, Tsai MK, Tsao CK, Lippman SM, Wu XF (2015) The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling. Clin Cancer Res 21(1):193–200. https://doi.org/10.1158/1078-0432.Ccr-14-0748 CrossRefPubMed Wen CP, Zhang FM, Liang D, Wen C, Gu J, Skinner H, Chow WH, Ye YQ, Pu X, Hildebrandt MAT, Huang MS, Chen CH, Hsiung CA, Tsai MK, Tsao CK, Lippman SM, Wu XF (2015) The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling. Clin Cancer Res 21(1):193–200. https://​doi.​org/​10.​1158/​1078-0432.​Ccr-14-0748 CrossRefPubMed
41.
go back to reference Temme EHM, Zhang JJ, Schouten EG, Kesteloot H (2001) Serum bilirubin and 10-year mortality risk in a Belgian population. Cancer Cause Control 12(10):887–894. doi:Doi 10.1023/A:1013794407325CrossRef Temme EHM, Zhang JJ, Schouten EG, Kesteloot H (2001) Serum bilirubin and 10-year mortality risk in a Belgian population. Cancer Cause Control 12(10):887–894. doi:Doi 10.1023/A:1013794407325CrossRef
44.
go back to reference Grzybowska-Szatkowska L, Rzymowska J, Slaska B (2016) Oxidative phosphorylation genes in breast cancer cells. Int J Mol Med 38:S78–S78 Grzybowska-Szatkowska L, Rzymowska J, Slaska B (2016) Oxidative phosphorylation genes in breast cancer cells. Int J Mol Med 38:S78–S78
45.
go back to reference Marini C, Bianchi G, Buschiazzo A, Ravera S, Martella R, Bottoni G, Petretto A, Emionite L, Monteverde E, Capitanio S, Inglese E, Fabbi M, Bongioanni F, Garaboldi L, Bruzzi P, Orengo AM, Raffaghello L, Sambuceti G (2016) Divergent targets of glycolysis and oxidative phosphorylation result in additive effects of metformin and starvation in colon and breast cancer. Sci Rep. https://doi.org/10.1038/srep19569 CrossRefPubMedPubMedCentral Marini C, Bianchi G, Buschiazzo A, Ravera S, Martella R, Bottoni G, Petretto A, Emionite L, Monteverde E, Capitanio S, Inglese E, Fabbi M, Bongioanni F, Garaboldi L, Bruzzi P, Orengo AM, Raffaghello L, Sambuceti G (2016) Divergent targets of glycolysis and oxidative phosphorylation result in additive effects of metformin and starvation in colon and breast cancer. Sci Rep. https://​doi.​org/​10.​1038/​srep19569 CrossRefPubMedPubMedCentral
50.
Metadata
Title
Breast cancer risk in relation to plasma metabolites among Hispanic and African American women
Authors
Hua Zhao
Jie Shen
Steven C. Moore
Yuanqing Ye
Xifeng Wu
Francisco J. Esteva
Debasish Tripathy
Wong-Ho Chow
Publication date
01-08-2019
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05165-4

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