Most cancer cells express insulin and insulin growth factor (IGF)-I receptors (IGF1R); the A isoform of the insulin receptor is commonly expressed. The A receptor isoform can stimulate insulin-mediated mitogenesis, even in cells deficient in IGF1R.7 Apart from the direct effects of insulin on cancer cells, it is possible that hyperinsulinemia
promotes carcinogenesis indirectly through its effects on IGF-1.8 Moreover, insulin resistance, which is a key underlying feature of type 2 diabetes mellitus, is part of the metabolic syndrome and is also associated with hyperlipidemia (hypertriglyceridemia and hypo high-density lipoprotein Alisertib cell line cholesterol, obesity, and hypertension).9,10 Trevisan et al. reported that metabolic syndrome significantly increases cancer risk, especially in men.11 In the present
study, we anticipated an intimate association between the SNP, rs6983267 at 8q24, which is one of the most important SNPs expected to contribute to the carcinogenesis of CRC, and diabetes mellitus or hyperlipidemia. We also assumed that interaction of both genes might be a notable risk factor of CRC. We performed analysis of rs6983267 at 8q24, array-CGH, and cDNA-array in Japanese CRC patients to clarify the active molecule in carcinogenesis initiated by diabetes mellitus or hyperlipidemia. find more This study was designed to analyze the correlation between the genotype of an SNP, rs6983267, at 8q24 and genetic risk factors of diabetes mellitus and hyperlipidemia. Newly diagnosed cases of CRC were identified in eight institutes (Kyushu University Hospital, Kitazato University, National Cancer Center Hospital, Northern Yokohama Hospital Showa University, National Defense Medical College Hospitals, Tokyo Medical and Dental University Hospital, Mie University Hospital, and Takano Hospital) from 2003 to 2008. All 189 participants gave documented
informed content. 上海皓元医药股份有限公司 From among these patients, 134 patients’ array-CGH and cDNA-array data were available. We investigated 107 patients whose medical history of diabetes and hyperlipidemia was clearly documented. Ten patients with diabetes and seven with hyperlipidemia, who diagnosed and received treatment for each disease, were included. Clinical characteristics of 15 patients with diabetes or hyperlipidemia are shown in Table 1. The Ethical Committee of each institute approved this project. Genomic DNA was extracted from samples using conventional methodologies and quantified using PicoGreen (Invitrogen, Carlsbad, CA, USA). The TaqMan probes and primers for rs6983267 were purchased from Applied Biosystems, Carlsbad, CA, USA. Genotyping was performed with the ABI 7900HT Sequence Detection System and sds 2.0 software (Applied Biosystems). We evaluated the correlation between the morbidity of CRC and SNP rs6983267 at the 8q24 locus.