title: Decreased risk of colorectal cancer with the high natural killer cell activity NKG2D genotype in Japanese.
abstract: BACKGROUND
  NKG2D is an immune receptor on natural killer (NK) and other cells active in the immune system. It recognizes ligands expressed on mainly transformed cells and plays a role in their elimination through the so-called 'cancer immune surveillance'. It was reported that there are two haplotypes of NKG2D, HNK1 (high NK activity) and LNK1 (low NK activity). Harboring the HNK1 is reported to reduce the overall cancer risk. To elucidate its impact on colorectal cancer (CRC), we conducted the present case-control study.
  
  
  METHODS
  The subjects were 379 CRC patients and 1137 sex-age-matched non-cancer controls. Data on lifestyle factors including diet were obtained by self-administered questionnaire. The NKG2D genotypes (rs1049174: G-C, LNK1/LNK1:CC; LNK1/HNK1:CG and HNK1/HNK1:GG) were assessed by the TaqMan method. Associations were then assessed by multivariate logistic regression models, considering potential confounders. The measure of association was the odds ratio (OR) and its confidence intervals (CIs).
  
  
  RESULTS
  We found a reduced risk of CRC with the NKG2D HNK1. Adjusted ORs were 0.77 for LNK1/HNK1 (95% CI: 0.60-0.99) and 0.48 for HNK1/HNK1 (0.32-0.72) relative to LNK1/LNK1. The same association was consistently observed with stratified analyses across all confounders except regular exercise and body mass index (BMI). Thus, the impact of harboring HNK1 was more evident among those with BMI >/= 25 and those exercising regularly, suggesting possible interactions between NKG2D genotype and these factors.
  
  
  CONCLUSIONS
  We found that the HNK1 genotype, associated with high NK cell activity, might be an independent protective factor for CRC among the Japanese population. This possibility warrants further analysis.
authors.affiliation: Central Laboratory and Radiation Biology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Furue
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kumimoto
authors.forename: Akio
authors.initials: A
authors.lastname: Hiraki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Koji
authors.initials: K
authors.lastname: Komori
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Kanemitsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirai
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kato
authors.forename: Minoru
authors.initials: M
authors.lastname: Ueda
authors.forename: Kanji
authors.initials: K
authors.lastname: Ishizaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007107:Immune System; D007564:Japan; D007694:Killer Cells, Natural / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000235:genetics*; D055607:Receptors, Natural Killer Cell; D012306:Risk
chemical_list: C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell