title: The 8.1 ancestral MHC haplotype is strongly associated with colorectal cancer risk.
abstract: Many recent data indicate that some alleles encoded in the central major histocompatibility complex (MHC) region (Class III) of short arm of chromosome 6 may modify the risk of cancer development. Therefore we determined 4 single nucleotide polymorphisms (SNPs) of this region (TNF-alpha -308 G > A, RAGE -429 T > C, HSP70-2 -1267 A > G, LTA 252 A > G) in genomic DNA samples from 183 Hungarian patients with colorectal cancer and 141 age matched control subjects representing the Hungarian population of the same age and gender. No significant differences were found in either SNP tested. When, however, three- or four-locus haplotypes consisting of known constituents of the so-called 8.1 ancestral haplotype (8.1AH) were considered, marked differences were observed. Frequency of TNF-alpha -308A, RAGE -429C, HSP70-2 -1267G, LTA 252G (8.1AH) haplotype was significantly (p = 0.006) more frequent (19.1%) among patients than in the controls (7.7%). Age- and gender-adjusted ratio of the 8.1AH carriers vs. non-carriers to have colorectal cancer was 2.514 (1.130-5.594). This risk was higher in <or=67 years old subjects (4.073 (1.317-12.596)) and in females (3.771 (1.302-10.927). These findings-consistent with similar recent results with ovarian cancer-indicate that carriers of the 8.1AH, encoding for an altered immune response and known to be associated with alterations of several immune functions and autoimmune diseases have an increased risk for some cancer types. These findings may contribute to better understanding how the defense mechanisms against tumors could be enhanced/strengthened.
authors.affiliation: 3rd Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Eva Katalin
authors.initials: EK
authors.lastname: Tóth
authors.forename: Judit
authors.initials: J
authors.lastname: Kocsis
authors.forename: Balázs
authors.initials: B
authors.lastname: Madaras
authors.forename: Adrienn
authors.initials: A
authors.lastname: Bíró
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Pocsai
authors.forename: George
authors.initials: G
authors.lastname: Fust
authors.forename: Bernadett
authors.initials: B
authors.lastname: Blaskó
authors.forename: István
authors.initials: I
authors.lastname: Karádi
authors.forename: Róza
authors.initials: R
authors.lastname: Adány
authors.forename: Judit
authors.initials: J
authors.lastname: Laki
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D037102:Lectins / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D037102:Lectins; D014409:Tumor Necrosis Factor-alpha; C027112:fucose-binding lectin