Serum methylmalonic acid concentrations at breast cancer diagnosis significantly correlate with clinical frailty.
Breast cancer
Clinical frailty
Methylmalonic acid
Mobility
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
26 Aug 2023
26 Aug 2023
Historique:
received:
11
05
2023
accepted:
04
08
2023
medline:
27
8
2023
pubmed:
27
8
2023
entrez:
26
8
2023
Statut:
aheadofprint
Résumé
Methylmalonic acid (MMA), a by-product of propionate metabolism, is known to increase with age. This study investigates the potential of serum MMA concentrations as a biomarker for age-related clinical frailty in older patients with breast cancer. One hundred nineteen patients ≥ 70 years old with early-stage breast cancer were included (median age 76 years). G8 screening, full geriatric assessment, clinical parameters (i.e., estimated glomerular filtration rate (eGFR) and body mass index (BMI)), and serum sample collection were collected at breast cancer diagnosis before any therapy was administered. MMA concentrations were measured via liquid chromatography with tandem mass spectrometry. MMA concentrations significantly increased with age and eGFR (all P < 0.001) in this older population. The group with an abnormal G8 (≤ 14, 51% of patients) had significantly higher MMA levels than the group with normal G8 (> 14, 49%): 260 nmol/L vs. 188 nmol/L, respectively (P = 0.0004), even after correcting for age and eGFR (P = 0.001). Furthermore, in the detailed assessment, MMA concentrations correlated most with mobility (Eastern Cooperative Oncology Group (ECOG) Performance Status and Activities of Daily Living (ADL) tools, all P ≤ 0.02), comorbidity (Charlson Comorbidity Index (CCI) tool, P = 0.005), and polypharmacy (P < 0.001), whereas no significant associations were noted for instrumental ADL (IADL), Mini-Mental State Examination (MMSE), Geriatric Depression Scale-15 (GDS15), Mini Nutritional Assessment-Short Form (MNA-SF), and pain (all P > 0.1). In addition, our results showed that higher MMA levels correlate with poor overall survival in breast cancer patients (P = 0.003). Elevated serum MMA concentrations at initial diagnosis are significantly associated, not only with age but also independently with clinical frailty, suggesting a possible influence of MMA on clinical frailty in older patients with early-stage breast cancer.
Identifiants
pubmed: 37632634
doi: 10.1007/s11357-023-00908-0
pii: 10.1007/s11357-023-00908-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s), under exclusive licence to American Aging Association.
Références
Forny P, et al. Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: first revision. J Inherit Metab Dis. 2021;44:566.
doi: 10.1002/jimd.12370
pubmed: 33595124
pmcid: 8252715
O’Shea CJ, et al. Neurocognitive phenotype of isolated methylmalonic acidemia. Pediatrics. 2012;129:e1541-51.
doi: 10.1542/peds.2011-1715
pubmed: 22614770
pmcid: 3362903
Cosson MA, et al. Long-term outcome in methylmalonic aciduria: a series of 30 French patients. Mol Genet Metab. 2009;97:172–8.
doi: 10.1016/j.ymgme.2009.03.006
pubmed: 19375370
Sun S, Jin H, Rong Y, Song W, Li Q. Methylmalonic acid levels in serum, exosomes, and urine and its association with cblC type methylmalonic acidemia-induced cognitive impairment. Front Neurol. 2022;13:1090958.
doi: 10.3389/fneur.2022.1090958
pubmed: 36582607
pmcid: 9792485
Jiang YZ, Sun LY. The value of liver transplantation for methylmalonic acidemia. Front Pediatr. 2019;7:87.
doi: 10.3389/fped.2019.00087
pubmed: 30949461
pmcid: 6437036
Manoli I, Sloan JL, Venditti CP. Isolated methylmalonic acidemia. GeneReviews® (University of Washington, Seattle, 1993).
van der Meer SB, et al. Clinical outcome of long-term management of patients with vitamin B12-unresponsive methylmalonic acidemia. J Pediatr. 1994;125:903–8.
doi: 10.1016/S0022-3476(05)82005-0
pubmed: 7996362
Vogiatzoglou A, et al. Determinants of plasma methylmalonic acid in a large population: implications for assessment of vitamin B12 status. Clin Chem. 2009;55:2198–206.
doi: 10.1373/clinchem.2009.128678
pubmed: 19833840
Ganji V, Kafai MR. Population reference values for serum methylmalonic acid concentrations and its relationship with age, sex, race-ethnicity, supplement use, kidney function and serum vitamin B12 in the post-folic acid fortification period. Nutrients. 2018;10:74.
doi: 10.3390/nu10010074
pubmed: 29329201
pmcid: 5793302
Song X, Mitnitski A, Rockwood K. Prevalence and 10-year outcomes of frailty in older adults in relation to deficit accumulation. J Am Geriatr Soc. 2010;58:681–7.
doi: 10.1111/j.1532-5415.2010.02764.x
pubmed: 20345864
Giaquinto AN, et al. Breast cancer statistics, 2022. CA Cancer J Clin. 2022;72:524–41.
doi: 10.3322/caac.21754
pubmed: 36190501
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33.
doi: 10.3322/caac.21708
pubmed: 35020204
Wolff AC, et al. Human epidermal growth factor receptor 2 testing in breast cancer: american society of clinical oncology/college of american pathologists clinical practice guideline focused update. J Clin Oncol. 2018;36:2105–22.
doi: 10.1200/JCO.2018.77.8738
pubmed: 29846122
Kenis C, et al. Adherence to geriatric assessment-based recommendations in older patients with cancer: a multicenter prospective cohort study in Belgium. Ann Oncol. 2018;29:1987–94.
doi: 10.1093/annonc/mdy210
pubmed: 29905766
Bellera CA, et al. Screening older cancer patients: first evaluation of the G-8 geriatric screening tool. Ann Oncol. 2012;23:2166–72.
doi: 10.1093/annonc/mdr587
pubmed: 22250183
Inker LA, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021;385:1737–49.
doi: 10.1056/NEJMoa2102953
pubmed: 34554658
pmcid: 8822996
Mineva EM, et al. Age-specific reference ranges are needed to interpret serum methylmalonic acid concentrations in the US population. Am J Clin Nutr. 2019;110:158–68.
doi: 10.1093/ajcn/nqz045
pubmed: 31127807
Kameda M, Teruya T, Yanagida M, Kondoh H. Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility. Proc Natl Acad Sci U S A. 2020;117:9483–9.
doi: 10.1073/pnas.1920795117
pubmed: 32295884
pmcid: 7196897
Rattray NJW, et al. Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty. Nat Commun. 2019;10:5027.
doi: 10.1038/s41467-019-12716-2
pubmed: 31690722
pmcid: 6831565
Marron MM, et al. A metabolite composite score attenuated a substantial portion of the higher mortality risk associated with frailty among community-dwelling older adults. J Gerontol Ser A. 2021;76:378–84.
doi: 10.1093/gerona/glaa112
Chandler RJ, et al. Metabolic phenotype of methylmalonic acidemia in mice and humans: the role of skeletal muscle. BMC Med Genet. 2007;8:1–11.
doi: 10.1186/1471-2350-8-64
Dutra JC, et al. Inhibition of succinate dehydrogenase and β-hydroxybutyrate dehydrogenase activities by methylmalonate in brain and liver of developing rats. J Inherit Metab Dis. 1993;16:147–53.
doi: 10.1007/BF00711328
pubmed: 8487494
Østergaard E, Wibrand F, Ørngreen MC, Vissing J, Horn N. Impaired energy metabolism and abnormal muscle histology in mut– methylmalonic aciduria. Neurology. 2005;65:931–3.
doi: 10.1212/01.wnl.0000176065.80560.26
pubmed: 16186538
Costa RT, Santos MB, Alberto-Silva C, Carrettiero DC, Ribeiro CAJ. Methylmalonic acid impairs cell respiration and glutamate uptake in C6 rat glioma cells: implications for methylmalonic acidemia. Cell Mol Neurobiol. 2022. https://doi.org/10.1007/s10571-022-01236-1 .
doi: 10.1007/s10571-022-01236-1
pubmed: 35674974
de Souza Almeida RR, et al. Methylmalonic acid induces inflammatory response and redox homeostasis disruption in C6 astroglial cells: potential glioprotective roles of melatonin and resveratrol. Amino Acids. 2022;54:1505–17.
doi: 10.1007/s00726-022-03191-z
pubmed: 35927507
Decker Y, et al. Decreased pH in the aging brain and Alzheimer’s disease. Neurobiol Aging. 2021;101:40–9.
doi: 10.1016/j.neurobiolaging.2020.12.007
pubmed: 33578193
Wang C, et al. Association between methylmalonic acid and cognition: a systematic review and meta-analysis. Front Pediatr. 2022;10:901956.
doi: 10.3389/fped.2022.901956
pubmed: 35844735
pmcid: 9276928
Brown RT, et al. Association of functional impairment in middle age with hospitalization, nursing home admission, and death. JAMA Intern Med. 2019;179:668–75.
doi: 10.1001/jamainternmed.2019.0008
pubmed: 30958504
pmcid: 6503566
López-Gómez JJ, et al. Malnutrition at diagnosis in amyotrophic lateral sclerosis (als) and its influence on survival: using glim criteria. Clin Nutr. 2021;40:237–44.
doi: 10.1016/j.clnu.2020.05.014
pubmed: 32507583
Hshieh TT, et al. Prevalence of cognitive impairment and association with survival among older patients with hematologic cancers. JAMA Oncol. 2018;4:686–93.
doi: 10.1001/jamaoncol.2017.5674
pubmed: 29494732
pmcid: 5885202