MHC Class II alleles in ulcerative colitis-associated colorectal cancer

Garrity‐Park, Megan; Loftus, Edward V.; Sandborn, William J.; Bryant, Sandra C.; Smyrk, Thomas C.

doi:10.1136/gut.2008.166686

Cited by 31 publications

(29 citation statements)

References 43 publications

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“…Therefore, the data presented herein suggest that the presence of HLA-DR13 alleles can also be associated with an increased susceptibility to develop CRC in patients with no signs of ulcerative colitis, indicating that HLA-DR13 alleles are linked to CRC tumors developed in colonic tissues with 13 and without IBDs. The choice to use the SBT methodology, for DRB1*13 typing, has provided more detailed information than that achieved by the sequence-specific oligonucleotides-PCR methodology used by Garrity-Park et al in the detection of alleles associated with CRC tumors.…”

Section: Discussionmentioning

confidence: 97%

“…[13][14][15] This information has provided the rationale to investigate the role of DRB1 alleles on the susceptibility to develop CRC tumors in patients with no history of IBDs. In our study, using the SBT methodology, DRB1*13 polymorphisms were analyzed in 53 CRC patients without a history of IBDs and in 57 sex-and agematched healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…12 Garrity-Park et al showed that the presence of particular HLA-DRB1 alleles may also reduce or increase the risk of developing ulcerative colitis-associated colorectal cancer (CRC). 13 However, the link between HLA-DRB1 allele frequency (AF) and CRC tumor, developed in the absence of IBDs, is unknown. The aim of our study was to determine whether there is an association between CRC tumors developed in the absence of an IBD background and HLA-DRB1 alleles.…”

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confidence: 99%

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HLA‐DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma

Aureli

Canossi

Beato

et al. 2014

Intl Journal of Cancer

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Increasing evidence suggests that HLA-DRB1 alleles reduce or increase the risk of developing ulcerative colitis-associated colorectal carcinoma (CRC) tumors. However, the role of HLA-DRB1 locus on the susceptibility to develop CRC tumor, in the absence of a history of inflammatory bowel diseases (IBDs), is unclear. The aim of our study was to determine whether HLA-DRB1 alleles are associated with IBD-independent CRC tumor. HLA-DRB1 allele polymorphisms were identified by sequence-based typing method in 53 CRC patients and 57 sex-and age-matched healthy Caucasian controls. Pearson's chisquared analysis with Yate's correction or Fisher's exact test with Bonferroni's correction, as appropriate, were used to compare the allele frequency (AF) differences of HLA-DRB1 in patients and controls. A total of 29 HLA-DRB1 alleles were recognized. A detailed study of these alleles allowed to identify DRB1*13:01 and DRB1*11:01 alleles that were significantly associated with an increased and reduced risk to develop CRC tumor, respectively. AF of DRB1*13:01, in CRC patients, was significantly higher than that of healthy controls, even following Bonferroni's correction (p 5 0.029). In contrast, the presence of the DRB1*11:01 allele was negatively associated with CRC tumor as evidenced by the significantly lower AF in CRC patients than that of healthy controls (p 5 0.005). However, following Bonferroni's correction, the AF of DRB*11:01 lost its statistical significance. These results suggest that HLA-DRB1*13:01 allele could be a potential marker for predicting genetic susceptibility to CRC tumor. In contrast, the protective role of DRB1*11:01 remains unclear.HLA-class II antigens (HLA-DR, DQ and DP) are key players of the immune response. They present extracellular antigen peptides to CD41 T cells.1 HLA class II antigens are expressed on the cell surface of immune cells such as B lymphocytes, activated CD41T cells, antigen-presenting cells including Langerhans and dendritic cells, macrophages and vascular endothelial cells, but not on connective and epithelial cells. 3-5 Importantly, HLA class II antigen expression in solid tumor cells has been associated with favorable and unfavorable prognosis of CRC patients.6-9 The reason(s) why that happens is (are) uncertain.8 HLA class II antigen polymorphisms have been also implicated in conferring genetic susceptibility to immune-mediated diseases and tumors.For example, the presence of HLA class II alleles DRB3*02/03 (DR52), DRB1*13 and DRB1*03 (DR17) was associated with an increased risk to develop cervical cancer, while DRB1*09:01:02 and DRB5*01/02 (DR51) were protective alleles.10 Lin et al. showed that DRB1*07 and DRB1*12 are associated with an increased risk to develop hepatocellular carcinoma.11 Conversely, Chaudhuri et al. found that HLA DQB1*03:03:02 and DRB1*11 alleles are instead associated with a reduced risk of breast cancer.12 Garrity-Park et al. showed that the presence of particular HLA-DRB1 alleles may also reduce or increase the risk of developing

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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HLA‐DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma

Aureli

Canossi

Beato

et al. 2014

Intl Journal of Cancer

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“…While the HLA DR17 gene was noted in a higher frequency in the ulcerative colitis-colorectal cancer patients, HLA-DR7, -DR1 or -DQ5 alleles were noted at a significantly higher frequency in ulcerative colitis "control" cases that did not develop colorectal cancer. 20 In another study, women carrying the HLA-DQB1*0301 allele exhibited an increased risk of developing cervical intraepithelial neoplasia when infected by HPV 16 and this allele was also overrepresented in cervical intraepithelial neoplasia grade III cases in comparison to cervical intraepithelial neoplasia grade II cases. 21 The HLA class I allele A*02 was associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV positive Hodgkin's lymphoma.…”

Section: History Of Hla and Prognosismentioning

confidence: 99%

Survival of the fittest or best adapted: HLA-dependent tumor development

Masucci¹,

Andersson²,

Villabona³

et al. 2010

J Nucleic Acids Invest

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The major histocompatibility complex (MHC) comprises a set of genes that are critical to immunity and surveillance against neoplastic transformation. There is increasing evidence that the MHC antigens not only regulate antitumor immune responses in experimental animal models but directly correlate with survival and prognosis of patients with diverse types of cancers. MHC antigens may in the future function as potential biomarkers for prognosis and allow selection of cancer patients for intensive therapy.

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“…To date, GWAS studies point to >30 genetic loci/genes for susceptibility to CD and UC, with several shared loci involved in the Th-17 response (NOD2, IL23R, IL12B, JAK2, STAT3) [12][13][14]. Allelic differences in the class II human leukocyte antigens (HLA) on chromosome 6 are associated with both increased and decreased risk of CA-CRC [15]. Interestingly, loss of heterozygosity (LOH) on chromosome 6 has been previously reported as a unique feature of CA-CRC, distinguishing it from sporadic CRC and UC [16].…”

Section: Introductionmentioning

confidence: 99%

A Two-Locus System Controls Susceptibility to Colitis-Associated Colon Cancer in Mice

et al. 2010

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AbstrAct:We have previously shown that the differential susceptibility of A/J (susceptible) and C57BL/6J (B6, resistant) mouse strains to azoxymethane (AOM)-induced colorectal cancer (CRC) is controlled by the chromosome 3 locus, Ccs3. We report that A/J and B6 mice also show differential susceptibility to colitis-associated colorectal cancer (CA-CRC) induced by combined administration of AOM and dextran sulfate. This differential susceptibility is not controlled by Ccs3, but is under distinct genetic control. Linkage analyses in (A/J x B6)F2 mice detected a major CA-CRC susceptibility locus on chromosome 9 (Ccs4) which controls tumor multiplicity and tumor surface area. Susceptibility alleles at Ccs4 are inherited in a recessive fashion, with A/J alleles being associated with susceptibility. We also detected a second locus on chromosome 14 that acts in an additive fashion with Ccs4. Strikingly, F2 mice homozygous for A/J alleles at both loci (Ccs4 and chromosome 14) are as susceptible to CA-CRC as the A/J controls while mice homozygous for B6 alleles are as resistant as the B6 controls, thus supporting the role of two interacting loci in this CA-CRC model. This indicates that susceptibility to chemically-induced CRC and susceptibility to CA-CRC are under distinct genetic control in mice, and probably involve distinct cellular pathways.

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MHC Class II alleles in ulcerative colitis-associated colorectal cancer

Abstract: We report a significant association between specific HLA alleles and either the risk for (DR17) or protection from (DR7, DQ5) UC-CRC. This suggests a possible genetic predisposition for increased UC-CRC risk. In addition, DQ2 and DR17 were associated with CIITA methylation.

Cited by 31 publications

References 43 publications

HLA‐DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma

HLA‐DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma

Survival of the fittest or best adapted: HLA-dependent tumor development

A Two-Locus System Controls Susceptibility to Colitis-Associated Colon Cancer in Mice

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