The 8.1 ancestral MHC haplotype is strongly associatied with colorectal cancer

Abstract

10548 Background: The immune system is believed to play an important role in sufficiently or insufficiently inhibiting the multistep process of tumour development. The so-called 8.1 ancestral haplotype (8.1AH) in the main histocompatibility complex is associated with alterations of the immune response characterized by an increase in antibodies, circulating immune complexes and TNF-a, and lack of a complement protein component (C4A). Methods: To study the possible association of the 8.1AH with colorectal cancer the DNA samples of 183 hungarian patients (average age 67.99 ys; 63–74 ys) with colorectal cancer and 129 healthy hungarian controls (average age 66.5 ys; 60–73.5 ys) were genotyped for member alleles of the 8.1 AH: AGER -429C, HSP70–2 -1267G (HSP70–2G), TNF- a -308A (TNF2) and LTA+252G by SSP-PCR and PCR-RFLP. Simultaneous carriage of the four member alleles was considered carriage of the 8.1AH. Results: We found the frequency of the 8.1AH to be significantly higher in patients with colorectal cancer than in healthy controls (19.1% vs. 7%, P=0.002). After adjustment to age and gender individuals carrying the 8.1AH had a 2.81 (1.23–6.22, P=0.011) fold risk to develop colorectal cancer compared with non-carriers of the haplotype. None of the member alleles alone showed association with colorectal cancer (PAGER-429C=0.486; PHSP70–2G=0.898; PTNF2=0.140; PLTA=0.376.) Conclusions: The 8.1AH by the genetically encoded alterations of the immune response may affect the development of colorectal cancer. The frequency of the 8.1AH is 5–10% in Hungary/Central Europe but, for instance, approx. 20–25% in the populations with Celtic origin. Our novel observation might contribute to cancer research and therapy when more information is available on which key components of the altered immune response encoded by the 8.1AH are not effective enough against tumor development. No significant financial relationships to disclose.