Details of Disease

Disease Name

Colorectal adenocarcinoma

large bowel adenocarcinoma; adenocarcinoma of large bowel; large intestine adenocarcinoma; adenocarcinoma of large intestine; adenocarcinoma of the large bowel; adenocarcinoma of the large intestine; colorectal (colon or rectal) adenocarcinoma; colorectal adenocarcinoma; colorectum adenocarcinoma

Definition

The most common type of colorectal carcinoma. It is characterized by the presence of malignant glandular epithelial cells invading through the muscularis mucosa into the submucosa. Histologic variants include mucinous adenocarcinoma, signet ring cell carcinoma, medullary carcinoma, serrated adenocarcinoma, cribriform comedo-type adenocarcinoma, and micropapillary adenocarcinoma.|Editor note: we follow NCIT in treating colorectal and large intestine as equivalent

Disease Hierarchy

DIS3IHTY: Adenocarcinoma

DIS5PYL0: Colorectal carcinoma

DISPQOUB: Colorectal adenocarcinoma

Disease Identifiers

MONDO ID

MONDO_0005008

UMLS CUI

C1319315

MedGen ID

230816

HPO ID

HP:0040275

SNOMED CT ID

408645001

General Information of Disease (ID: DISPQOUB)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 58 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
DSG3	TTEO4P8	Limited	Biomarker	[1]
EIF5A	TTIVCNR	Limited	Altered Expression	[2]
EIF5A2	TTH53G9	Limited	Biomarker	[2]
IMP3	TTEJA2R	Limited	Altered Expression	[3]
KDM2A	TT8XTY2	Limited	Altered Expression	[4]
LAMP2	TTULDG7	Limited	Biomarker	[5]
MMP16	TTNP4CU	Limited	Posttranslational Modification	[6]
RTN4R	TTVRZUO	Limited	Biomarker	[7]
S100A3	TTCDFR1	Limited	Biomarker	[8]
S100A6	TT716MY	Limited	Biomarker	[9]
SLC25A1	TTTD730	Limited	Altered Expression	[10]
BAX	TTQ57WJ	moderate	Altered Expression	[11]
FBXW7	TT29KY7	moderate	Genetic Variation	[12]
KISS1R	TT3KBZY	moderate	Altered Expression	[13]
MDM2	TT9TE0O	moderate	Altered Expression	[14]
MET	TTNDSF4	moderate	Altered Expression	[15]
MLH1	TTISG27	moderate	Biomarker	[16]
MSH2	TTCAWRT	moderate	Altered Expression	[17]
TYMS	TTP1UKZ	moderate	Altered Expression	[18]
BMP4	TTD3BSX	Strong	Genetic Variation	[19]
BRAF	TT0EOB8	Strong	Biomarker	[20]
CDH1	TTLAWO6	Strong	Genetic Variation	[21]
CDH3	TTARMD9	Strong	Genetic Variation	[19]
CRHR2	TTIY658	Strong	Altered Expression	[22]
CUBN	TT9YLCR	Strong	Genetic Variation	[23]
CYP17A1	TTRA5BZ	Strong	Genetic Variation	[24]
DDC	TTN451K	Strong	Altered Expression	[25]
EPHA5	TTV9KOD	Strong	Genetic Variation	[26]
ERAP1	TT60XFL	Strong	Genetic Variation	[23]
F2RL2	TTVSEBF	Strong	Altered Expression	[27]
FADS2	TTT2VDU	Strong	Genetic Variation	[28]
FKBP5	TT0J5KQ	Strong	Genetic Variation	[19]
FSCN1	TTTRS9B	Strong	Altered Expression	[29]
GATA3	TT45KOB	Strong	Genetic Variation	[30]
GREM1	TTOUZN5	Strong	Genetic Variation	[28]
HRAS	TT28ZON	Strong	Altered Expression	[31]
IGFBP6	TTLAYV8	Strong	Altered Expression	[32]
KCNH1	TT9XKUC	Strong	Genetic Variation	[33]
KISS1	TTU2O6T	Strong	Altered Expression	[13]
LPAR1	TTQ6S1K	Strong	Genetic Variation	[19]
LRP1	TTF2V7I	Strong	Genetic Variation	[19]
NOTCH4	TTXDIK2	Strong	Genetic Variation	[34]
PIGU	TT2LHI6	Strong	Genetic Variation	[19]
PRKCZ	TTBSN0L	Strong	Altered Expression	[27]
RET	TT4DXQT	Strong	Altered Expression	[35]
ROS1	TTSZ6Y3	Strong	Altered Expression	[36]
SH2B3	TT36N7Z	Strong	Genetic Variation	[28]
SLC22A16	TTITAVR	Strong	Genetic Variation	[37]
SLC22A3	TTG2UMS	Strong	Genetic Variation	[38]
SLCO2A1	TTKVTQO	Strong	Genetic Variation	[34]
SMAD6	TTON5JB	Strong	Genetic Variation	[19]
SMAD7	TT0J32Z	Strong	Genetic Variation	[28]
SMAD9	TTX8EBV	Strong	Genetic Variation	[19]
TCF7L2	TT80QAL	Strong	Genetic Variation	[34]
TDP2	TTYF26D	Strong	Genetic Variation	[39]
TRPC6	TTRBT3W	Strong	Genetic Variation	[19]
ERBB2	TTR5TV4	Definitive	Biomarker	[40]
HSPE1	TTWYMFE	Definitive	Altered Expression	[41]
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⏷ Show the Full List of 58 DTT(s)

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A26	DT8HR5O	Strong	Genetic Variation	[19]
SLC6A18	DTGQ7FH	Strong	Genetic Variation	[19]
------------------------------------------------------------------------------------

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
SMOX	DEOH5V3	Limited	Biomarker	[42]
UPP1	DEFZWAX	Limited	Altered Expression	[43]
------------------------------------------------------------------------------------

This Disease Is Related to 129 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BNIP2	OTVZD4H6	Limited	Biomarker	[44]
CDH17	OT9EV2XK	Limited	Biomarker	[45]
E2F4	OTB3JFH4	Limited	Altered Expression	[46]
EMX2	OT0V8OYK	Limited	Altered Expression	[47]
FABP6	OTIRQWLW	Limited	Altered Expression	[48]
GOLGA5	OTG6HB6U	Limited	Biomarker	[49]
KLK11	OT5PKX7Y	Limited	Biomarker	[50]
LETM1	OT8N4MRU	Limited	Altered Expression	[51]
MACC1	OTV3DLX0	Limited	Altered Expression	[52]
MSH6	OT46FP09	Limited	Genetic Variation	[53]
NBEAL2	OTMCAXWR	Limited	Biomarker	[54]
NEURL1	OT2C4P70	Limited	Biomarker	[55]
PARP6	OTWSXW4O	Limited	Altered Expression	[56]
PDHX	OTG7O271	Limited	Altered Expression	[57]
PIWIL1	OT7CRGZ3	Limited	Biomarker	[58]
PIWIL4	OTDA9MY0	Limited	Biomarker	[58]
RPH3AL	OT9VFJEL	Limited	Genetic Variation	[59]
SH3GLB1	OTAZ5OP8	Limited	Altered Expression	[60]
TSPAN1	OTZQPIYK	Limited	Altered Expression	[61]
PKHD1	OTAH8SMF	Disputed	Biomarker	[62]
CFHR1	OT72R16T	moderate	Biomarker	[63]
CTTNBP2	OT4CL1EW	moderate	Altered Expression	[64]
PMS2	OTNLWTMI	moderate	Biomarker	[65]
RETREG1	OTYOSLZX	moderate	Altered Expression	[66]
SPINK1	OTSUVAL2	moderate	Genetic Variation	[67]
ACOXL	OTW680HT	Strong	Genetic Variation	[30]
ACTR1B	OTGBCKLO	Strong	Genetic Variation	[21]
ACTRT3	OT2U08K8	Strong	Genetic Variation	[21]
APC	OTKV0TIK	Strong	Genetic Variation	[19]
APOC1	OTA58CED	Strong	Biomarker	[68]
ATF1	OT251CI0	Strong	Genetic Variation	[19]
ATOH1	OTBZYG2R	Strong	Biomarker	[69]
BAALC	OTUZSRVF	Strong	Genetic Variation	[70]
BABAM1	OTCFPER6	Strong	Genetic Variation	[33]
BICC1	OTYRKIJ1	Strong	Genetic Variation	[24]
BMP5	OTC0Y6E0	Strong	Genetic Variation	[19]
BOC	OTXBCY9W	Strong	Genetic Variation	[19]
BRD8	OTIKS3PC	Strong	ModifyingMutation	[71]
BTBD9	OTWQ6GA3	Strong	Genetic Variation	[72]
CABLES2	OTGD9A2A	Strong	Genetic Variation	[28]
CBLN2	OT29SSBE	Strong	Genetic Variation	[72]
CCND2	OTDULQF9	Strong	Genetic Variation	[28]
CFAP44	OT1273MD	Strong	Genetic Variation	[72]
CHD1	OT9R9G0H	Strong	Genetic Variation	[19]
CHRDL2	OTJU2I5H	Strong	Genetic Variation	[19]
CLEC3A	OTTOAEGT	Strong	Genetic Variation	[39]
COL4A2	OTJK1LKN	Strong	Genetic Variation	[19]
COLCA1	OT8BP6UD	Strong	Genetic Variation	[28]
CRTC3	OTVIGVUW	Strong	Genetic Variation	[21]
DCBLD1	OTA702JK	Strong	Genetic Variation	[73]
DCC	OT2C1SHW	Strong	Altered Expression	[74]
DENND5B	OTNDJJUR	Strong	Genetic Variation	[34]
DIP2B	OTP6KH82	Strong	Genetic Variation	[23]
DOCK3	OTF3YS2W	Strong	Genetic Variation	[72]
DRG1	OTIFYMI3	Strong	Genetic Variation	[72]
ECT2L	OTOSDMGV	Strong	Genetic Variation	[39]
EFCAB2	OTXEFI4O	Strong	Genetic Variation	[34]
EIF4ENIF1	OTZWDB2X	Strong	Genetic Variation	[72]
ELOVL5	OT375W1Z	Strong	Genetic Variation	[75]
ETV6	OTCZMG61	Strong	Genetic Variation	[76]
FAM193A	OTT0W53G	Strong	Genetic Variation	[72]
FBXL20	OTVTR1KY	Strong	Biomarker	[77]
FEN1	OT6QGG7O	Strong	Genetic Variation	[21]
FMN1	OT9CID5R	Strong	Genetic Variation	[19]
FRY	OT74IAG2	Strong	Genetic Variation	[33]
GNAS	OTMH8BKJ	Strong	Genetic Variation	[34]
GNG12	OTOGF42G	Strong	Genetic Variation	[72]
GPATCH1	OTQRDBY6	Strong	Genetic Variation	[78]
GPR143	OTWUA2AV	Strong	Genetic Variation	[79]
HERC2	OTNQYKOB	Strong	Genetic Variation	[72]
HHIP	OT77RQYS	Strong	Genetic Variation	[19]
HLA-F	OT76CM19	Strong	Genetic Variation	[72]
HNF1B	OTSYIC3T	Strong	Genetic Variation	[33]
HSPA12A	OTFOCDD6	Strong	Genetic Variation	[80]
KCNIP4	OTB1BS0X	Strong	Genetic Variation	[72]
KLF5	OT1ABI9N	Strong	Genetic Variation	[19]
KRT8	OTTM4X11	Strong	Genetic Variation	[33]
L1TD1	OTB2W20Y	Strong	Genetic Variation	[34]
LAMA5	OTIIXE4M	Strong	Genetic Variation	[19]
LAMC1	OTIG527N	Strong	Genetic Variation	[28]
LIMA1	OTONPC9R	Strong	Genetic Variation	[81]
LRIG1	OTY5HZN5	Strong	Genetic Variation	[28]
LSAMP	OTYXVQX2	Strong	Genetic Variation	[39]
MACF1	OTVIHD77	Strong	Genetic Variation	[82]
MAMSTR	OT4J6Z7G	Strong	Genetic Variation	[21]
MTX1	OTLSDNZO	Strong	Genetic Variation	[83]
MUC2	OT3X4QVX	Strong	Altered Expression	[84]
MYNN	OT61R1HP	Strong	Genetic Variation	[85]
MYO16	OTMS3D8W	Strong	Genetic Variation	[72]
MYRF	OTKF6AEB	Strong	Genetic Variation	[34]
MZF1	OTMVZCPW	Strong	Genetic Variation	[19]
NEK10	OTN0JAYL	Strong	Genetic Variation	[33]
NXN	OT35N40G	Strong	Genetic Variation	[19]
OR1J2	OTIQTQHU	Strong	Genetic Variation	[72]
PARD3	OTH5BPLO	Strong	Altered Expression	[27]
PCNX1	OTFP8XHC	Strong	Genetic Variation	[82]
PLCH1	OT6Z1L2E	Strong	Genetic Variation	[86]
PLEKHG6	OTZWA27A	Strong	Genetic Variation	[19]
PNKD	OT6G9UXN	Strong	Genetic Variation	[28]
POLD3	OTEQEFQ2	Strong	Genetic Variation	[28]
POU5F1B	OT0FKQ51	Strong	Genetic Variation	[28]
PPP1R21	OTWN6N7T	Strong	Genetic Variation	[34]
PREX1	OTUTPVA9	Strong	Genetic Variation	[34]
RAD51B	OTCJVRMY	Strong	Genetic Variation	[33]
RALY	OT78NNWY	Strong	Genetic Variation	[33]
RETREG3	OTEUQ2MI	Strong	Genetic Variation	[39]
RHPN2	OTTYWMF6	Strong	Genetic Variation	[28]
RIPOR3	OTHZ4RKK	Strong	Genetic Variation	[19]
RNF4	OTCMXQRE	Strong	Genetic Variation	[72]
RNGTT	OT59E0KX	Strong	Genetic Variation	[39]
RTEL1	OTI3PJCT	Strong	Genetic Variation	[19]
SATB2	OT2W80XC	Strong	Biomarker	[87]
SBF2	OTBB8NO8	Strong	Genetic Variation	[21]
SCAF8	OTSCFMK3	Strong	Genetic Variation	[39]
SHROOM2	OTZ2FJ7Q	Strong	Genetic Variation	[21]
SPINT1	OT1CLR5L	Strong	Altered Expression	[88]
SPSB2	OT7ZVT8R	Strong	Genetic Variation	[24]
SYMPK	OTYAUDXV	Strong	Genetic Variation	[78]
TANC1	OTF6TZ8E	Strong	Genetic Variation	[19]
TBX3	OTM64N7K	Strong	Genetic Variation	[89]
TET2	OTKKT03T	Strong	Genetic Variation	[19]
TFEB	OTJUJJQY	Strong	Genetic Variation	[21]
TMBIM1	OTE47B57	Strong	Genetic Variation	[28]
TMEM258	OTXSDU14	Strong	Genetic Variation	[34]
TMTC1	OTZ7NW96	Strong	Genetic Variation	[39]
TNS3	OTPG2D8Z	Strong	Genetic Variation	[21]
TOX2	OT7RZRVK	Strong	Genetic Variation	[19]
TTC22	OTFNNLI1	Strong	Genetic Variation	[19]
DLD	OT378CU9	Definitive	Biomarker	[90]
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⏷ Show the Full List of 129 DOT(s)

References

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12	FBXW7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma.Oncotarget. 2017 Jun 13;8(24):39268-39279. doi: 10.18632/oncotarget.16848.
13	KISS1 and KISS1R expression in primary and metastatic colorectal cancer.J BUON. 2018 May-Jun;23(3):598-603.
14	Expression of p53 and mdm2 mRNA and protein in colorectal carcinomas.Eur J Cancer. 1999 Jul;35(7):1083-8. doi: 10.1016/s0959-8049(99)00058-1.
15	MET amplification, expression, and exon 14 mutations in colorectal adenocarcinoma.Hum Pathol. 2018 Jul;77:108-115. doi: 10.1016/j.humpath.2018.03.024. Epub 2018 Apr 8.
16	Immunoexpression of TS, p53, COX2, EGFR, MSH6 and MLH1 biomarkers and its correlation with degree of differentiation, tumor staging and prognostic factors in colorectal adenocarcinoma: a retrospective longitudinal study.Sao Paulo Med J. 2019 May 8;137(1):33-38. doi: 10.1590/1516-3180.2018.0270071218.
17	HMSH2 and HMSH6 gene expression profiles in colorectal adenocarcinoma in patients up to 50 years of age.Biomed Pharmacother. 2016 Oct;83:602-606. doi: 10.1016/j.biopha.2016.07.015. Epub 2016 Jul 25.
18	Correlation between thymidylate synthase gene variants, RNA and protein levels in primary colorectal adenocarcinomas.J Int Med Res. 2010 Mar-Apr;38(2):484-97. doi: 10.1177/147323001003800212.
19	Discovery of common and rare genetic risk variants for colorectal cancer.Nat Genet. 2019 Jan;51(1):76-87. doi: 10.1038/s41588-018-0286-6. Epub 2018 Dec 3.
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21	Association analyses identify 31 new risk loci for colorectal cancer susceptibility.Nat Commun. 2019 May 14;10(1):2154. doi: 10.1038/s41467-019-09775-w.
22	Corticotropin-releasing factor receptor subtype 2 in human colonic mucosa: down-regulation in ulcerative colitis.World J Gastroenterol. 2013 Mar 7;19(9):1416-23. doi: 10.3748/wjg.v19.i9.1416.
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24	Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk.Gastroenterology. 2016 Jun;150(7):1633-1645. doi: 10.1053/j.gastro.2016.02.076. Epub 2016 Mar 8.
25	L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study.BMC Cancer. 2012 Oct 20;12:484. doi: 10.1186/1471-2407-12-484.
26	Genome wide association study to identify predictors for severe skin toxicity in colorectal cancer patients treated with cetuximab.PLoS One. 2018 Dec 17;13(12):e0208080. doi: 10.1371/journal.pone.0208080. eCollection 2018.
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29	Overexpression of fascin-1 in advanced colorectal adenocarcinoma: tissue microarray analysis of immunostaining scores with clinicopathological parameters.Dis Markers. 2007;23(3):153-60. doi: 10.1155/2007/685163.
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32	Association of IGFBP-6 Expression with Metabolic Syndrome and Adiponectin and IGF-IR Receptor Levels in Colorectal Cancer.Asian Pac J Cancer Prev. 2016;17(8):3963-9.
33	Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.Cancer Res. 2016 Sep 1;76(17):5103-14. doi: 10.1158/0008-5472.CAN-15-2980. Epub 2016 Apr 20.
34	Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.Gastroenterology. 2019 Apr;156(5):1455-1466. doi: 10.1053/j.gastro.2018.11.066. Epub 2018 Dec 6.
35	RET fusions in solid tumors.Cancer Treat Rev. 2019 Dec;81:101911. doi: 10.1016/j.ctrv.2019.101911. Epub 2019 Oct 30.
36	ALK and ROS1 overexpression is very rare in colorectal adenocarcinoma.Appl Immunohistochem Mol Morphol. 2015 Feb;23(2):134-8. doi: 10.1097/PAI.0000000000000025.
37	Associations of single nucleotide polymorphisms with mucinous colorectal cancer: genome-wide common variant and gene-based rare variant analyses.Biomark Res. 2018 Jun 13;6:17. doi: 10.1186/s40364-018-0133-z. eCollection 2018.
38	Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population.Gut. 2011 Jun;60(6):799-805. doi: 10.1136/gut.2010.215947. Epub 2011 Jan 17.
39	Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.Sci Rep. 2015 Dec 1;5:17369. doi: 10.1038/srep17369.
40	HER-2 inhibition in gastric and colorectal cancers: tangible achievements, novel acquisitions and future perspectives.Oncotarget. 2016 Oct 18;7(42):69060-69074. doi: 10.18632/oncotarget.11264.
41	Comparative analysis of Hsp10 and Hsp90 expression in healthy mucosa and adenocarcinoma of the large bowel.Anticancer Res. 2014 Aug;34(8):4153-9.
42	Extracellular Signals of a Human Epithelial Colorectal Adenocarcinoma (Caco-2) Cell Line Facilitate the Penetration of Pseudomonas aeruginosa PAO1 Strain through the Mucin Layer.Front Cell Infect Microbiol. 2017 Sep 21;7:415. doi: 10.3389/fcimb.2017.00415. eCollection 2017.
43	Gene expression of 5-fluorouracil metabolic enzymes in primary colorectal cancer and corresponding liver metastasis.Cancer Chemother Pharmacol. 2004 May;53(5):391-6. doi: 10.1007/s00280-003-0747-0. Epub 2004 Jan 20.
44	miR-20a targets BNIP2 and contributes chemotherapeutic resistance in colorectal adenocarcinoma SW480 and SW620 cell lines.Acta Biochim Biophys Sin (Shanghai). 2011 Mar;43(3):217-25. doi: 10.1093/abbs/gmq125. Epub 2011 Jan 17.
45	Combination of cadherin-17 and SATB homeobox 2 serves as potential optimal makers for the differential diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal adenocarcinoma.Oncotarget. 2017 Jun 28;8(38):63442-63452. doi: 10.18632/oncotarget.18828. eCollection 2017 Sep 8.
46	Expression of E2F-4 gene in colorectal adenocarcinoma and corresponding covering mucosa: an immunohistochemistry, image analysis, and immunoblot study.Appl Immunohistochem Mol Morphol. 2002 Sep;10(3):225-30. doi: 10.1097/00129039-200209000-00007.
47	EMX2 gene expression predicts liver metastasis and survival in colorectal cancer.BMC Cancer. 2017 Aug 22;17(1):555. doi: 10.1186/s12885-017-3556-2.
48	A novel variant of ileal bile acid binding protein is up-regulated through nuclear factor-kappaB activation in colorectal adenocarcinoma.Cancer Res. 2007 Oct 1;67(19):9039-46. doi: 10.1158/0008-5472.CAN-06-3690.
49	Site-specific gene expression profiles and novel molecular prognostic factors in patients with lower gastrointestinal adenocarcinoma diffusely metastatic to liver or peritoneum.Ann Surg Oncol. 2007 Dec;14(12):3460-71. doi: 10.1245/s10434-007-9557-7. Epub 2007 Sep 25.
50	KLK11 mRNA expression predicts poor disease-free and overall survival in colorectal adenocarcinoma patients.Biomark Med. 2014;8(5):671-85. doi: 10.2217/bmm.13.151.
51	LETM1 is a potential cancer stem-like cell marker and predicts poor prognosis in colorectal adenocarcinoma.Pathol Res Pract. 2019 Jul;215(7):152437. doi: 10.1016/j.prp.2019.152437. Epub 2019 May 5.
52	Heterogeneity analysis of Metastasis Associated in Colon Cancer 1 (MACC1) for survival prognosis of colorectal cancer patients: a retrospective cohort study.BMC Cancer. 2015 Mar 21;15:160. doi: 10.1186/s12885-015-1150-z.
53	MSH6 gene pathogenic variant identified in familial pancreatic cancer in the absence of colon cancer.Eur J Gastroenterol Hepatol. 2020 Mar;32(3):345-349. doi: 10.1097/MEG.0000000000001617.
54	A qualitative transcriptional signature for determining the grade of colorectal adenocarcinoma.Cancer Gene Ther. 2020 Sep;27(9):680-690. doi: 10.1038/s41417-019-0139-1. Epub 2019 Oct 9.
55	Clinicopathological relevance of HER2/neu and a related gene-protein cubic regression correlation in colorectal adenocarcinomas in Taiwan.Int J Oncol. 2005 Apr;26(4):933-43.
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