Polymorphisms of the apoptosis-associated gene DP1L1 (deleted in polyposis 1-like 1) in colon cancer and inflammatory bowel disease.
OBJECTIVE
The deleted-in-polyposis1-like1 (DP1L1) gene displays pro-apoptotic activity and was proposed to be a tumor suppressor. It locates on chromosome 19p13.3, which harbors the locus for Peutz-Jeghers-Syndrome and is deleted in various tumors. We analyzed the association of DP1L1 polymorphisms with colon cancer, and cancer-associated Ulcerative colitis and Crohn's disease.


METHODS
Fifty-eight patients with colon cancer, 18 with Ulcerative colitis, 18 with Crohn's disease, and 70 control individuals were genotyped for SNPs at positions 992 and 996 of DP1L1 cDNA.


RESULTS
Homozygous carriers of 992A alleles comprised 16% of the control group but were significantly increased in colon cancer with a frequency of 36% (P = 0.013 cancer vs control). Homozygous 991-A was also elevated in Ulcerative colitis (N = 18) with a frequency of 33%. In contrast, 18 patients with Crohn's disease showed no difference in frequency of 992AA (22%) compared to control. The A-allele of the adjacent C996A polymorphism has a low frequency (3.5%) in the control population, but significantly increased frequency of 13% in colon cancer (P = 0.0149 for allele frequency, Fisher's exact). 996-A allele frequency is also increased in inflammatory bowel disease (IBD): 22% of Ulcerative colitis- and 50% of Crohn's disease-patients were heterozygous carriers of 996-A (P = 0.052 for CU and P < 0.0001 for MC vs controls).


CONCLUSIONS
DP1L1 polymorphisms are associated with colon cancer and IBD. This indicates that DP1L1 plays a functional role in these conditions. Thus DP1L1 may be a diagnostic and therapeutic target for colon cancer and IBD.
Wellmann
Axel
A
Institute of Pathology Celle, Wittingerstrasse 14, 29223 Celle, Germany. axel_wellmann@yahoo.com
Fogt
Franz
F
Hollerbach
Stephan
S
Hahne
Jens
J
Koenig-Hoffmann
Kerstin
K
Smeets
Daniela
D
Brinkmann
Ulrich
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D002470:Cell Survival; D003093:Colitis, Ulcerative / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics; D053938:DNA Fragmentation; D018076:DNA, Complementary / Q000032:analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010957:Plasmids; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics; D055815:Young Adult
D018076:DNA, Complementary; D005136:Eye Proteins