Chronic shoulder pain/disability is a significant cause of morbidity among breast cancer survivors, which can persist for several years postsurgery, thus markedly impacting their quality of life. The condition is a multifactorial and polygenic trait. In this overarching context, we report here on the polygenic effects through polymorphisms in opioid signaling and pain pathways, specifically, the (1) ATP-binding cassette subfamily B, member 1 gene–catechol-O-methyltransferase (ABCB1-COMT) and (2) ABCB1-opioid receptor Mu 1 (OPRM1)-COMT genes. Using TaqMan™ assays, we genotyped the polymorphisms in the candidate genes in a sample of South African breast cancer survivors (N = 252) reporting chronic shoulder pain/disability. The Shoulder Pain and Disability Index was used to evaluate pain/disability symptoms, with total scores converted to percentages and participants categorized as no-low (< 30%) or moderate-high (≥ 30%). The ABCB1 (rs1128503)-COMT (rs4680) G–A allele combination was significantly associated with increased pain (p = 0.005, odds ratio [OR]: 2.08, 95% confidence interval [CI]: 1.12–3.84) and combined (p = 0.008, OR: 1.94, 95% CI: 1.02–3.69) symptoms. Furthermore, the ABCB1 (rs1045642)-OPRM1 (rs1799971)-COMT (rs4680) G–A–A allele combination was associated with increased pain (p < 0.001, OR: 1.93, 95% CI: 1.01–3.69) and combined (p < 0.001, OR: 1.60, 95% CI: 0.81–3.19) symptoms. Collectively, these findings suggest that chronic shoulder pain/disability in breast cancer survivors in this sample of South African patients is influenced by the combined effects of polymorphisms within the ABCB1-OPRM1-COMT genes. These observations present the potential for further translational research, personalized medicine, and pain management strategies to improve the long-term quality of life in breast cancer patients.
Abrahams-OctoberZ, JohnsonR, BenjeddouM, et al.The determination of the effect(s) of solute carrier family 22-member 2 (SLC22A2) haplotype variants on drug binding via molecular dynamic simulation systems. Sci Rep, 2022; 12(1):16936; doi: 10.1038/s41598-022-21291-4
2.
AdamczykK, ZuzdaK, JankowskiM, et al.Effects of opioids in cancer pain: An interplay among genetic factors, immune response, and clinical outcomes-a scoping review. Cancers (Basel), 2025; 17(5):863; doi: 10.3390/cancers17050863
3.
AdzhubeiI, JordanDM, SunyaevSR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet, 2013;Chapter 7(1):Unit7 20; doi: 10.1002/0471142905.hg0720s76
4.
AdzhubeiIA, SchmidtS, PeshkinL, et al.A method and server for predicting damaging missense mutations. Nat Methods, 2010; 7(4):248–249; doi: 10.1038/nmeth0410-248
5.
AllemaniC, MatsudaT, Di CarloV, et al.; CONCORD Working Group. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): Analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018; 391(10125):1023–1075; doi: 10.1016/S0140-6736(17)33326-3
6.
AllemaniC, WeirHK, CarreiraH, et al.; CONCORD Working Group. Global surveillance of cancer survival 1995-2009: Analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet, 2015; 385(9972):977–1010; doi: 10.1016/S0140-6736(14)62038-9
7.
AubrunF, ZahrN, LangeronO, et al.Opioid-related genetic polymorphisms do not influence postoperative opioid requirement: A prospective observational study. Eur J Anaesthesiol, 2018; 35(7):496–504; doi: 10.1097/EJA.0000000000000793
8.
BaberM, ChaudhryS, KellyL, et al.The pharmacogenetics of codeine pain relief in the postpartum period. Pharmacogenomics J, 2015; 15(5):430–435; doi: 10.1038/tpj.2015.3
9.
BarrattDT, CollerJK, HallinanR, et al.ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics. Pharmgenomics Pers Med, 2012; 5:53–62; doi: 10.2147/PGPM.S29272
10.
BastamiS, GuptaA, ZackrissonAL, et al.Influence of UGT2B7, OPRM1 and ABCB1 gene polymorphisms on postoperative morphine consumption. Basic Clin Pharmacol Toxicol, 2014; 115(5):423–431; doi: 10.1111/bcpt.12248
11.
BelliniMI, LoriE, ForteF, et al.Thyroid and renal cancers: A bidirectional association. Front Oncol, 2022; 12:951976; doi: 10.3389/fonc.2022.951976
12.
BenavidesR, VsevolozhskayaO, CattaneoS, et al.A functional polymorphism in the ATP-Binding Cassette B1 transporter predicts pharmacologic response to combination of nortriptyline and morphine in neuropathic pain patients. Pain, 2020; 161(3):619–629; doi: 10.1097/j.pain.0000000000001750
13.
BoujelbeneN, CosinschiA, BoujelbeneN, et al.Pure seminoma: A review and update. Radiat Oncol, 2011; 6(1):90; doi: 10.1186/1748-717X-6-90
14.
CacabelosR, TorrellasC. Pharmacoepigenomics. In: Medical Epigenetics. (TollefsbolTO, ed.) Academic Press: Boston, 2016; pp. 585–617.
15.
CampbellCM, EdwardsRR. Ethnic differences in pain and pain management. Pain Manag, 2012; 2(3):219–230; doi: 10.2217/pmt.12.7
16.
CandiottiK, YangZ, XueL, et al.Single-nucleotide polymorphism C3435T in the ABCB1 gene is associated with opioid consumption in postoperative pain. Pain Med, 2013; 14(12):1977–1984; doi: 10.1111/pme.12226
17.
ChenX, GaoB, PonnusamyM, et al.MEF2 signaling and human diseases. Oncotarget, 2017; 8(67):112152–112165; doi: 10.18632/oncotarget.22899
18.
ChiuYH, HsuCY, LuML, et al.Augmentation strategies for clozapine-resistant patients with schizophrenia. Curr Pharm Des, 2020; 26(2):218–227; doi: 10.2174/1381612826666200110102254
19.
ChrischillesEA, RileyD, LetuchyE, et al.Upper extremity disability and quality of life after breast cancer treatment in the Greater Plains Collaborative clinical research network. Breast Cancer Res Treat, 2019; 175(3):675–689; doi: 10.1007/s10549-019-05184-1
20.
CockburnDM. Tuberous sclerosis (Bourneville’s disease): An illustrated review. Clinical and Experimental Optometry, 1991; 74(2):49–50; doi: 10.1111/j.1444-0938.1991.tb04608.x
21.
ColuzziF, ScerpaMS, RoccoM, et al.The impact of P-glycoprotein on opioid analgesics: What’s the real meaning in pain management and palliative care? Int J Mol Sci, 2022; 23(22):14125; doi: 10.3390/ijms232214125
22.
CordellHJ. Detecting gene-gene interactions that underlie human diseases. Nat Rev Genet, 2009; 10(6):392–404; doi: 10.1038/nrg2579
23.
CrawfordDC, NickersonDA. Definition and clinical importance of haplotypes. Annu Rev Med, 2005; 56:303–320; doi: 10.1146/annurev.med.56.082103.104540
De GregoriM, DiatchenkoL, IngelmoPM, et al.Human genetic variability contributes to postoperative morphine consumption. J Pain, 2016; 17(5):628–636; doi: 10.1016/j.jpain.2016.02.003
26.
de WitE, DelportW, RugamikaCE, et al.Genome-wide analysis of the structure of the South African Coloured Population in the Western Cape. Hum Genet, 2010; 128(2):145–153; doi: 10.1007/s00439-010-0836-1
27.
DiatchenkoL, SladeGD, NackleyAG, et al.Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet, 2005; 14(1):135–143; doi: 10.1093/hmg/ddi013
28.
DuffyA, VerbanckM, DobbynA, et al.Tissue-specific genetic features inform prediction of drug side effects in clinical trials. Sci Adv, 2020; 6(37):eabb6242; doi: 10.1126/sciadv.abb6242
29.
DurhamJT, BrandOM, ArnoldM, et al.Myospryn is a direct transcriptional target for MEF2A that encodes a striated muscle, alpha-actinin-interacting, costamere-localized protein. J Biol Chem, 2006; 281(10):6841–6849; doi: 10.1074/jbc.M510499200
30.
ErbiI, CiantelliM, FarinellaR, et al.Role of OPRM1, clinical and anthropometric variants in neonatal pain reduction. Sci Rep, 2020; 10(1):7091; doi: 10.1038/s41598-020-63790-2
31.
FatumoS, ChikoworeT, KalyesubulaR, et al.Discovery and fine-mapping of kidney function loci in first genome-wide association study in Africans. Hum Mol Genet, 2021; 30(16):1559–1568; doi: 10.1093/hmg/ddab088
32.
FillingimRB. Individual differences in pain: Understanding the mosaic that makes pain personal. Pain, 2017; 158(Suppl 1):S11–S18; doi: 10.1097/j.pain.0000000000000775
33.
FirfireyF. The Relationship Between Genes Associated With The Pain Pathways And The Development Of Chronic Shoulder Pain And Disability In South African Breast Cancer Survivors In: Department of Human Biology. University of Cape Town: University of Cape Town Library, , 2024; p. 442.
34.
FirfireyF, SeptemberAV, ShamleyD. ABCB1 and OPRM1 single-nucleotide polymorphisms collectively modulate chronic shoulder pain and dysfunction in South African breast cancer survivors. Pharmacogenomics, 2022; 23(9):513–530; doi: 10.2217/pgs-2022-0020
35.
FirfireyF, ShamleyD, SeptemberAV. Polymorphisms in COMT and OPRM1 collectively contribute to chronic shoulder pain and disability in South African breast cancer survivor’s. Genes (Basel), 2023; 14(1):9; doi: 10.3390/genes14010009
GongXD, WangJY, LiuF, et al.Gene polymorphisms of OPRM1 A118G and ABCB1 C3435T may influence opioid requirements in Chinese patients with cancer pain. Asian Pac J Cancer Prev, 2013; 14(5):2937–2943; doi: 10.7314/apjcp.2013.14.5.2937
38.
GonzálezJ, ArmengolL, GuinóE, et al.SNPassoc: SNPs-based whole genome association studies. R Package Version, 2014; 1:2–9; doi: 10.1093/bioinformatics/btm025
39.
GrayK, AdhikarySD, JanickiP. Pharmacogenomics of analgesics in anesthesia practice: A current update of literature. J Anaesthesiol Clin Pharmacol, 2018; 34(2):155–160; doi: 10.4103/joacp.JOACP_319_17
40.
HamidovicA, HahnK, KolesarJ. Clinical significance of ABCB1 genotyping in oncology. J Oncol Pharm Pract, 2010; 16(1):39–44; doi: 10.1177/1078155209104380
41.
HiddingJT, BeurskensCH, van der WeesPJ, et al.Treatment related impairments in arm and shoulder in patients with breast cancer: A systematic review. PLoS One, 2014; 9(5):e96748; doi: 10.1371/journal.pone.0096748
42.
HigginbothamJA, MarkovicT, MassalyN, et al.Endogenous opioid systems alterations in pain and opioid use disorder. Front Syst Neurosci, 2022; 16:1014768; doi: 10.3389/fnsys.2022.1014768
43.
HoffmeyerS, BurkO, von RichterO, et al.Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A, 2000; 97(7):3473–3478; doi: 10.1073/pnas.97.7.3473
44.
HoofwijkDM, van ReijRR, RuttenBP, et al.Genetic polymorphisms and their association with the prevalence and severity of chronic postsurgical pain: A systematic review. Br J Anaesth, 2016; 117(6):708–719; doi: 10.1093/bja/aew378
45.
HoumesRJ, VoetsMA, VerkaaikA, et al.Efficacy and safety of tramadol versus morphine for moderate and severe postoperative pain with special regard to respiratory depression. Anesth Analg, 1992; 74(4):510–514; doi: 10.1213/00000539-199204000-00007
46.
HwangY, OhJ. The relationship between shoulder pain and shoulder disability in women: The mediating role of sleep quality and psychological disorders. Medicine (Baltimore), 2022; 101(41):e31118; doi: 10.1097/MD.0000000000031118
47.
IkediobiO, AouizeratB, XiaoY, et al.Analysis of pharmacogenetic traits in two distinct South African populations. Hum Genomics, 2011; 5(4):265–282; doi: 10.1186/1479-7364-5-4-265
48.
KhalilH, SereikaSM, DaiF, et al.OPRM1 and COMT gene-gene interaction is associated with postoperative pain and opioid consumption after orthopedic trauma. Biol Res Nurs, 2017; 19(2):170–179; doi: 10.1177/1099800416680474
49.
KlepstadP. Genetic variability and opioid efficacy. Current Anaesthesia & Critical Care, 2007; 18(3):149–156; doi: 10.1016/j.cacc.2007.06.001
50.
KniselyMR, ConleyYP, SmootB, et al.Associations Between Catecholaminergic and Serotonergic Genes and Persistent Arm Pain Severity Following Breast Cancer Surgery. J Pain, 2019; 20(9):1100–1111; doi: 10.1016/j.jpain.2019.03.008
51.
KoboriT, FujiwaraS, MiyagiK, et al.Involvement of moesin in the development of morphine analgesic tolerance through P-glycoprotein at the blood-brain barrier. Drug Metab Pharmacokinet, 2014; 29(6):482–489; doi: 10.2133/dmpk.DMPK-14-RG-042
52.
KolesnikovY, GabovitsB, LevinA, et al.Chronic pain after lower abdominal surgery: Do catechol-O-methyl transferase/opioid receptor mu-1 polymorphisms contribute? Mol Pain, 2013; 9:19; doi: 10.1186/1744-8069-9-19
53.
KowarikMC, EinhauserJ, JochimB, et al.Impact of the COMT Val(108/158)Met polymorphism on the mu-opioid receptor system in the human brain: Mu-opioid receptor, met-enkephalin and beta-endorphin expression. Neurosci Lett, 2012; 506(2):214–219; doi: 10.1016/j.neulet.2011.11.008
54.
KramerN, RamjithJ, ShamleyD. Prevalence of shoulder morbidity after treatment for breast Cancer in South Africa. Support Care Cancer, 2019; 27(7):2591–2598; doi: 10.1007/s00520-018-4540-3
55.
LeeMG, KimHJ, LeeKH, et al.The influence of genotype polymorphism on morphine analgesic effect for postoperative pain in children. Korean J Pain, 2016; 29(1):34–39; doi: 10.3344/kjp.2016.29.1.34
56.
LeeTS, KilbreathSL, RefshaugeKM, et al.Prognosis of the upper limb following surgery and radiation for breast cancer. Breast Cancer Res Treat, 2008; 110(1):19–37; doi: 10.1007/s10549-007-9710-9
57.
LevranO, O’HaraK, PelesE, et al.ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence. Hum Mol Genet, 2008; 17(14):2219–2227; doi: 10.1093/hmg/ddn122
58.
LittleJ, HigginsJP, IoannidisJP, et al.Strengthening the reporting of genetic association studies (STREGA)—An extension of the STROBE statement. Genet Epidemiol, 2009; 33(7):581–598; doi: 10.1002/gepi.20410
59.
LiuB, OuWC, FangL, et al.Myocyte enhancer factor 2A plays a central role in the regulatory networks of cellular physiopathology. Aging Dis, 2023; 14(2):331–349; doi: 10.14336/AD.2022.0825
60.
LiuN, NelsonBR, BezprozvannayaS, et al.Requirement of MEF2A, C, and D for skeletal muscle regeneration. Proc Natl Acad Sci U S A, 2014; 111(11):4109–4114; doi: 10.1073/pnas.1401732111
61.
LloydRA, HothamE, HallC, et al.Pharmacogenomics and patient treatment parameters to opioid treatment in chronic pain: A focus on morphine, oxycodone, tramadol, and fentanyl. Pain Med, 2017; 18(12):2369–2387; doi: 10.1093/pm/pnw317
62.
Lopez SotoEJ, CatanesiCI. Human population genetic structure detected by pain-related mu opioid receptor gene polymorphisms. Genet Mol Biol, 2015; 38(2):152–155; doi: 10.1590/S1415-4757382220140299
63.
LuL, ZhangJ, FanW, et al.Deregulated 14-3-3zeta and methionine adenosyltransferase alpha1 interplay promotes liver cancer tumorigenesis in mice and humans. Oncogene, 2021; 40(39):5866–5879; doi: 10.1038/s41388-021-01980-6
64.
MacDermidJC, SolomonP, PrkachinK. The Shoulder Pain and Disability Index demonstrates factor, construct and longitudinal validity. BMC Musculoskelet Disord, 2006; 7(1):12; doi: 10.1186/1471-2474-7-12
65.
ManworrenRC. Multimodal pain management and the future of a personalized medicine approach to pain. Aorn J, 2015; 101(3):308–314; quiz 315–308; doi: 10.1016/j.aorn.2014.12.009
66.
MartinKA, HumNR, SebastianA, et al.Methionine Adenosyltransferase 1a (MAT1A) enhances cell survival during chemotherapy treatment and is associated with drug resistance in bladder cancer PDX mice. Int J Mol Sci, 2019; 20(20):4983; doi: 10.3390/ijms20204983
67.
MatteiJ, ParnellLD, LaiCQ, et al.Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and non-Hispanic whites. BMC Genet, 2009; 10(1):45; doi: 10.1186/1471-2156-10-45
68.
MercerSL, CoopA. Opioid analgesics and P-glycoprotein efflux transporters: A potential systems-level contribution to analgesic tolerance. Curr Top Med Chem, 2011; 11(9):1157–1164; doi: 10.2174/156802611795371288
69.
MuraE, GovoniS, RacchiM, et al.Consequences of the 118A>G polymorphism in the OPRM1 gene: Translation from bench to bedside? J Pain Res, 2013; 6:331–353; doi: 10.2147/JPR.S42040
70.
NackleyAG, ShabalinaSA, TchivilevaIE, et al.Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science, 2006; 314(5807):1930–1933; doi: 10.1126/science.1131262
71.
NackleyAG, TanKS, FechoK, et al.Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors. Pain, 2007; 128(3):199–208; doi: 10.1016/j.pain.2006.09.022
NgPC, HenikoffS. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res, 2003; 31(13):3812–3814; doi: 10.1093/nar/gkg509
74.
NishiokaM, BundoM, KoikeS, et al.Comprehensive DNA methylation analysis of peripheral blood cells derived from patients with first-episode schizophrenia. J Hum Genet, 2013; 58(2):91–97; doi: 10.1038/jhg.2012.140
OertelBG, KettnerM, ScholichK, et al.A common human μ-opioid receptor genetic variant diminishes the receptor signaling efficacy in brain regions processing the sensory information of pain. J Biol Chem, 2009; 284(10):6530–6535; doi: 10.1074/jbc.M807030200
77.
PangGS, IthninF, WongYY, et al.A non-synonymous single nucleotide polymorphism in an OPRM1 splice variant is associated with fentanyl-induced emesis in women undergoing minor gynaecological surgery. PLoS One, 2012; 7(11):e48416; doi: 10.1371/journal.pone.0048416
78.
PeuckmannV, EkholmO, RasmussenNK, et al.Chronic pain and other sequelae in long-term breast cancer survivors: Nationwide survey in Denmark. Eur J Pain, 2009; 13(5):478–485; doi: 10.1016/j.ejpain.2008.05.015
79.
PfaffCL, ParraEJ, BonillaC, et al.Population structure in admixed populations: Effect of admixture dynamics on the pattern of linkage disequilibrium. Am J Hum Genet, 2001; 68(1):198–207; doi: 10.1086/316935
QianQJ, YangL, WangYF, et al.Gene-gene interaction between COMT and MAOA potentially predicts the intelligence of attention-deficit hyperactivity disorder boys in China. Behav Genet, 2010; 40(3):357–365; doi: 10.1007/s10519-009-9314-8
82.
QiuD, FriligkouE, HeJ, et al.Understanding the comorbidities among psychiatric disorders, chronic low back pain, and spinal degenerative disease using observational and genetically informed analyses. Biol Psychiatry Glob Open Sci, 2025; 5(6):100588; doi: 10.1016/j.bpsgos.2025.100588
83.
RajagopalVM, RajkumarAP, JacobKS, et al.Gene-gene interaction between DRD4 and COMT modulates clinical response to clozapine in treatment-resistant schizophrenia. Pharmacogenet Genomics, 2018; 28(1):31–35; doi: 10.1097/FPC.0000000000000314
84.
RajmanI, KnappL, HannaI. Genetic diversity in drug transporters: Impact in African populations. Clin Transl Sci, 2020; 13(5):848–860; doi: 10.1111/cts.12769
85.
ReganPM, SariyerIK, LangfordTD, et al.Morphine-induced MOR-1X and ASF/SF2 expressions are independent of transcriptional regulation: Implications for MOR-1X signaling. J Cell Physiol, 2016; 231(7):1542–1553; doi: 10.1002/jcp.25246
86.
Reyes-GibbyCC, SheteS, RakvagT, et al.Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene. Pain, 2007; 130(1–2):25–30; doi: 10.1016/j.pain.2006.10.023
87.
RiedererP, MullerT. Monoamine oxidase-B inhibitors in the treatment of Parkinson’s disease: Clinical-pharmacological aspects. J Neural Transm (Vienna), 2018; 125(11):1751–1757; doi: 10.1007/s00702-018-1876-2
88.
RoachKE, Budiman-MakE, SongsiridejN, et al.Development of a shoulder pain and disability index. Arthritis Care Res, 1991; 4(4):143–149.
89.
RoeckelLA, Le CozGM, Gaveriaux-RuffC, et al.Opioid-induced hyperalgesia: Cellular and molecular mechanisms. Neuroscience, 2016; 338:160–182; doi: 10.1016/j.neuroscience.2016.06.029
90.
SchaeferCP, TomeME, DavisTP. The opioid epidemic: A central role for the blood brain barrier in opioid analgesia and abuse. Fluids Barriers CNS, 2017; 14(1):32; doi: 10.1186/s12987-017-0080-3
91.
SchaidDJ, RowlandCM, TinesDE, et al.Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet, 2002; 70(2):425–434; doi: 10.1086/338688
92.
SchmackK, RosslerH, SekutowiczM, et al.Linking unfounded beliefs to genetic dopamine availability. Front Hum Neurosci, 2015; 9:521; doi: 10.3389/fnhum.2015.00521
93.
SerohijosAW, YinS, DingF, et al.Structural basis for mu-opioid receptor binding and activation. Structure, 2011; 19(11):1683–1690; doi: 10.1016/j.str.2011.08.003
94.
ShabalinaSA, ZaykinDV, GrisP, et al.Expansion of the human mu-opioid receptor gene architecture: Novel functional variants. Hum Mol Genet, 2009; 18(6):1037–1051; doi: 10.1093/hmg/ddn439
95.
ShabanguN, ThebeT, CaseyM, et al.Chronic pain in female breast cancer survivors–prevalence, characteristics and contributing factors: A cross-sectional pilot study. BMC Womens Health, 2023; 23(1):613; doi: 10.1186/s12905-023-02766-6
96.
ShamleyD, Lascurain-AguirrebenaI, OskrochiR, et al.Shoulder morbidity after treatment for breast cancer is bilateral and greater after mastectomy. Acta Oncol, 2012; 51(8):1045–1053; doi: 10.3109/0284186X.2012.695087
97.
ShamleyD, Lascurain-AguirrebenaI, OskrochiR. Clinical anatomy of the shoulder after treatment for breast cancer. Clin Anat, 2014; 27(3):467–477; doi: 10.1002/ca.22267
98.
ShamleyD. A cross-disciplinary look at shoulder pain and dysfunction after treatment for breast cancer. Int J Cancer Clin Res, 2015; 2(1); doi: 10.23937/2378-3419/2/1/1009
99.
ShihabHA, GoughJ, CooperDN, et al.Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models. Hum Mutat, 2013; 34(1):57–65; doi: 10.1002/humu.22225
100.
ShihabHA, RogersMF, GoughJ, et al.An integrative approach to predicting the functional effects of non-coding and coding sequence variation. Bioinformatics, 2015; 31(10):1536–1543; doi: 10.1093/bioinformatics/btv009
101.
SinghalP, VermaSS, RitchieMD. Gene interactions in human disease studies-evidence is mounting. Annu Rev Biomed Data Sci, 2023; 6:377–395; doi: 10.1146/annurev-biodatasci-102022-120818
SkorpenF, LaugsandEA, KlepstadP, et al.Variable response to opioid treatment: Any genetic predictors within sight? Palliat Med, 2008; 22(4):310–327; doi: 10.1177/0269216308089302
104.
SmartKM, BlakeC, StainesA, et al.Self-reported pain severity, quality of life, disability, anxiety and depression in patients classified with ‘nociceptive’, ‘peripheral neuropathic’ and ‘central sensitisation’ pain. The discriminant validity of mechanisms-based classifications of low back (+/−leg) pain. Man Ther, 2012; 17(2):119–125; doi: 10.1016/j.math.2011.10.002
TammimakiA, MannistoPT. Catechol-O-methyltransferase gene polymorphism and chronic human pain: a systematic review and meta-analysis. Pharmacogenet Genomics, 2012; 22(9):673–691; doi: 10.1097/FPC.0b013e3283560c46
108.
Team RdC. R: A language and environment for statistical computing. Team RdC; 2013.
109.
TengrupI, Tennvall-NittbyL, ChristianssonI, et al.Arm morbidity after breast-conserving therapy for breast cancer. Acta Oncol, 2000; 39(3):393–397; doi: 10.1080/028418600750013177
110.
TournierN, DeclèvesX, SaubaméaB, et al.Opioid transport by ATP-binding cassette transporters at the blood-brain barrier: Implications for neuropsychopharmacology. Curr Pharm Des, 2011; 17(26):2829–2842.
111.
VaserR, AdusumalliS, LengSN, et al.SIFT missense predictions for genomes. Nat Protoc, 2016; 11(1):1–9; doi: 10.1038/nprot.2015.123
112.
VieiraCMP, FragosoRM, PereiraD, et al.Pain polymorphisms and opioids: An evidence based review. Mol Med Rep, 2019; 19(3):1423–1434; doi: 10.3892/mmr.2018.9792
113.
Vultaggio-PomaV, SartiAC, Di VirgilioF. Extracellular ATP: A feasible target for cancer therapy. Cells, 2020; 9(11):2496; doi: 10.3390/cells9112496
114.
WangH, AnJ, ZhongS, et al.The influence of COMT and ABCB1 gene polymorphisms on sufentanil analgesic effect for postoperative pain in children with fracture. Medicine (Baltimore), 2024; 103(17):e37980; doi: 10.1097/MD.0000000000037980
115.
WangYN, YangWC, LiPW, et al.Myocyte enhancer factor 2A promotes proliferation and its inhibition attenuates myogenic differentiation via myozenin 2 in bovine skeletal muscle myoblast. PLoS One, 2018; 13(4):e0196255; doi: 10.1371/journal.pone.0196255
116.
WarnesG, LeischF, ManM, et al.Package ‘genetics’. CRAN: Rochester, NY; 2012.
117.
WolfSJ, BachtiarM, WangJ, et al.An update on ABCB1 pharmacogenetics: Insights from a 3D model into the location and evolutionary conservation of residues corresponding to SNPs associated with drug pharmacokinetics. Pharmacogenomics J, 2011; 11(5):315–325; doi: 10.1038/tpj.2011.16
118.
WolkingS, SchaeffelerE, LercheH, et al.Impact of genetic polymorphisms of ABCB1 (MDR1, P-glycoprotein) on drug disposition and potential clinical implications: Update of the literature. Clin Pharmacokinet, 2015; 54(7):709–735; doi: 10.1007/s40262-015-0267-1
119.
WuR, WangJ, YaoJ, et al.MEF2A regulates Calpain 3 expression in L6 myoblasts. Gene, 2018; 668:204–210; doi: 10.1016/j.gene.2018.05.056
120.
XiongY, WangL, JiangW, et al.MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. BMC Mol Biol, 2019; 20(1):8; doi: 10.1186/s12867-019-0125-z
121.
YaoP, DingYY, WangZB, et al.Effect of gene polymorphism of COMT and OPRM1 on the preoperative pain sensitivity in patients with cancer. Int J Clin Exp Med, 2015; 8(6):10036–10039. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26309696
122.
YapFY, SkalskiMR, PatelDB, et al.Hypertrophic osteoarthropathy: Clinical and imaging features. Radiographics, 2017; 37(1):157–195; doi: 10.1148/rg.2017160052
123.
YoshidaK, MullerDJ. Pharmacogenetics of antipsychotic drug treatment: Update and clinical implications. Mol Neuropsychiatry, 2020; 5(Suppl 1):1–26; doi: 10.1159/000492332
124.
YousifS, SaubameaB, CisterninoS, et al.Effect of chronic exposure to morphine on the rat blood-brain barrier: Focus on the P-glycoprotein. J Neurochem, 2008; 107(3):647–657; doi: 10.1111/j.1471-4159.2008.05647.x
125.
ZappeK, Cichna-MarklM. Aberrant DNA methylation of ABC transporters in cancer. Cells, 2020; 9(10):2281; doi: 10.3390/cells9102281
126.
ZhuB, CarmichaelRE, Solabre ValoisL, et al.The transcription factor MEF2A plays a key role in the differentiation/maturation of rat neural stem cells into neurons. Biochem Biophys Res Commun, 2018; 500(3):645–649; doi: 10.1016/j.bbrc.2018.04.125
127.
ZubietaJK, HeitzegMM, SmithYR, et al.COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science, 2003; 299(5610):1240–1243; doi: 10.1126/science.1078546
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