The human leukocyte antigen region and colorectal cancer risk.
OBJECTIVE
Recently, we found a certain haplotype in the human leukocyte antigen Class III subregion to be associated with breast cancer. Epidemiologic studies have shown that breast cancer and colorectal cancer have several risk factors in common. In view of these studies and because polymorphisms located in the human leukocyte antigen III region have been found to be associated with colorectal cancer, we wondered whether the same region also is involved in colorectal cancer susceptibility.


METHODS
The human leukocyte antigen region was genotyped with 14 microsatellite markers in germline DNA from 643 colorectal cancer patients and 841 family-based controls. Association analyses and the Haplotype Sharing Statistic were used to search for differences between patients and controls. Subgroup analyses were performed for gender, age at diagnosis, and localization of the tumor.


RESULTS
The Haplotype Sharing Statistic analysis revealed neither a difference in mean haplotype sharing between all patients and controls, nor in any of the subgroups. The single allele, genotype, and two-locus association analyses for all patients and for the different subgroups did not show an association with colorectal cancer for the 14 microsatellite markers. Also, no association was observed between the tumor necrosis factor-beta polymorphism and colorectal cancer.


CONCLUSIONS
No association was observed between commonly occurring haplotypes and alleles in the human leukocyte antigen region and colorectal cancer risk.
de Jong
Mirjam M
MM
Department of Gastroenterology, University Hospital Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Niens
Marijke
M
Nolte
Ilja M
IM
te Meerman
Gerard J
GJ
van der Graaf
Winette T A
WT
Mulder
Marcel J
MJ
van der Steege
Gerrit
G
Bruinenberg
Marcel
M
Schaapveld
Michael
M
Sijmons
Rolf H
RH
Hofstra
Robert M W
RM
de Vries
Elisabeth G E
EG
Kleibeuker
Jan H
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009426:Netherlands; D012042:Registries; D012307:Risk Factors
D005819:Genetic Markers; D006680:HLA Antigens