Carcinogenesis Advance Access published online on January 3, 2008
Carcinogenesis, doi:10.1093/carcin/bgm260
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Decreased risk of colorectal cancer with the high Natural-Killer (NK)-cell activity NKG2D genotype in Japanese
1 Central Laboratory and Radiation Biology
2 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi
3 Department of Pathology and Molecular Diagnosis
4 Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Aichi
5 Department of Oral and Maxillofacial Surgery
6 Department of Epidemiology, Nagoya University Graduate School of Medicine, Aichi
Requests for reprints: Keitaro Matsuo, Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. Phone: +81-52-762-6111; Fax: +81 52 763 5233; E-mail: kmatsuo{at}aichi-cc.jp.
Background: NKG2D is an immune receptor on 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 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 overall cancer risk. To elucidate its impact on colorectal cancer (CRC), we conducted the present case-control study.
Method: 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-to-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 (CI).
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 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.
Conclusion: 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.
Key Words: NKG2D Haplotype • NK cell activity • gene-environment interaction • lifestyle factor • colorectal cancer
Received August 21, 2007; revised October 22, 2007; accepted November 7, 2007.
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