Details

Autor(en) / Beteiligte

• Hayashi, Tomonori
• Morishita, Yukari
• Nagamura, Hiroko
• Maki, Mayumi
• Kusunoki, Yoichiro
• Yoshida, Kengo
• Imai, Kazue
• Cologne, John B.
• Nakachi, Kei

Titel

Abstract 4715: Genetic susceptibility to radiation-associated colon and rectum cancers among atomic-bomb survivors with special reference to the CD14 gene

Ist Teil von

• Cancer research (Chicago, Ill.), 2010-04, Vol.70 (8_Supplement), p.4715-4715

Erscheinungsjahr

2010

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Abstract Past epidemiology studies reported that atomic-bomb (A-bomb) radiation exposure enhanced risk of colon cancer, but not rectum cancer, among the survivors. The reason for this different sensitivity to radiation remains to be elucidated. Colorectal cancer is a multi-factorial disease, the onset of which is attributed to both environmental and genetic factors, with animal experiments showing that intestinal bacterial toxins accelerate carcinogenesis. It was recently reported that single nucleotide polymorphisms (SNPs) identified in the promoter region of CD14, encoding a receptor for the lipopolysaccharide component of the outer membrane of Gram-negative bacteria, regulate CD14 gene expression and thereby affect susceptibility to inflammatory diseases such as atopic dermatitis, coronary artery disease, and hepatic diseases. This study investigated relationship between a novel CD14 gene polymorphism and the development of radiation-associated colon and rectum cancers among an A-bomb survivor cohort, in terms of a case-cohort study. On the basis of this T/G polymorphism, we determined CD14 genotypes with 210 colorectal cancer cases and with a subcohort of 2,160 individuals who were randomly selected from the cohort. Our results showed that the individuals exposed to A-bomb radiation (≥5 mGy) were at an increased risk of colon cancer, but not rectum cancer, with relative risk (RR) of 1.19/Gy (95%CI: 1.04-1.36). When we divided the study subjects into three groups for radiation dose and into two groups for CD14 genotypes, significantly high risk of colon cancer was found with RR of 2.40 (95%CI: 1.37-4.23) for the combined category of CD14-T/T homozygote and the highest dose (≥0.7Gy), compared with the baseline category (CD14-T/G or G/G and no dose). These results suggest that CD14-related inflammatory response might be involved in the development of radiation-associated colon cancer, not rectum cancer, among A-bomb survivors, and that the CD14 genotyping might be involved in individual risk of colon cancer together with radiation dose. To find a functional significance of this polymorphism, we are currently working on ELISA-based assay to measure serum levels of soluble CD14 among healthy individuals in relation to the CD14 genotyping. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4715.