Increased frequency of the S allele of the L-myc oncogene in non-Hodgkin's lymphoma

Abstract

Summary We studied 100 patients with non-Hodgkin's lymphoma, 44 patients with Hodgkin's disease and 100 controls for the prevalence of the EcoRI restriction fragment polymorphism of the L-myc oncogene. No difference in the frequency of the three genotypes (LL, LS, SS) was found between the patient and control groups. However, the S allele was found to occur more frequently in the non-Hodgkin's lymphoma patients (X2 = 4.57, P = 0.032). These data confirm an earlier report and suggest that the presence of the S allele is associated with susceptibility to non-Hodgkin's lymphoma.Associations between restriction fragment length polymorphisms (RFLPs) of known oncogenes and a predisposition to develop cancer have been reported by a number of authors (Krontiris et al., 1985;Lidereau et al., 1985;Heighway et al., 1986). One of the most extensively studied oncogene RFLPs is an EcoRI RFLP of the L-myc oncogene. Digestion of DNA with EcoRI results in two alleles of 10 kb (L) and 6.6 kb (S). The S allele is reported to occur more frequently in male patients with bone and soft-tissue sarcomas (Kato et al., 1990), in oral cancer patients with poor to moderately differentiated tumours (Saranath et al., 1990) and in patients with leukaemia and lymphoma (Chenevix-Trench et al., 1989). Furthermore, an increased susceptibility to metastasis in lung (Kawashima et al., 1988), renal (Kakehi & Yoshida, 1989) and gastric cancer ) is associated with the presence of the S allele. However, a negative association between an increased susceptibility to metastases in Norwegian lung cancer patients and the S allele has been reported (Tefre et al., 1990). In this study we have investigated the frequency of the S allele in non-Hodgkin's lymphoma (NHL) patients and Hodgkin's disease (HD) patients compared with controls. al. (1988). Briefly, 5 ml of peripheral blood was lysed with 45 ml of cold lysis buffer (0.32 M sucrose, 10 mM Tris-HCl pH 7.5, 5 mM magnesium chloride and 1% Triton X-100) and then centrifuged for 10 min at 1,000 g. The pellet was resuspended in 5 ml of 4.0 M guanidine isothiocyanate, 25 mm sodium acetate and 0.84% P-mercaptoethanol and rocked gently for 20 min. The DNA was precipitated by the addition of an equal volume of isopropanol and resuspended in TE buffer (10 mM Tris-HCl, 1 mM EDTA, pH 8.0). A 3 ytg aliquot of DNA was digested with EcoRI, electrophoresed in a 0.8% agarose gel, transferred to Hybond N+ nylon membrane by alkaline transfer (Chomczynski & Qasba, 1984) and hybridised with a 32p_ labelled probe prepared by the random priming method of Feinberg and Vogelstein (1983). A 1.8 kb SmaI-EcoRI Lmyc fragment, pJB327 (Nau et al., 1985), excised from low gelling temperature agarose, was used as the probe. Washes were carried out at a final stringency of 0.3 x SSC and the autoradiographs exposed for 1-3 days on Kodak XAR-5 film at -80°C. Materials and methods Patients and controls StatisticsThe frequency of the three genotypes and the two alleles in the patient and control groups were compared using the X2 test. Results...

MYC oncogenes and human neoplastic disease

“…Scattered reports have suggested that individuals bearing the`short' (S) allele either have an increased incidence of certain tumors and/or that such tumors manifest a more aggressive behavior. The associated neoplasms include soft-tissue sarcomas (Kato et al, 1990), oral cancers (Saranath et al, 1990), colorectal cancers (Young et al, 1994), nonHodgkin's lymphoma (Crossen et al, 1994), breast cancer (Champeme et al, 1992), and non-SCLC lung cancer (Kawashima et al, 1988). In contrast, at least one report has suggested that the`SS' genotype protects against hepatocellular cancer (Taylor et al, 1993).…”

Limited-Stage Small Cell Lung Cancer: Current Chemoradiotherapy Treatment Paradigms

“…Historically, the routine use of PCI was met with skepticism because of retrospective reports of a high level of toxicity and a lack of a survival advantage. Poor functional outcomes in patients treated with PCI have been attributed to treatment with a high dose per fraction and a high total dose of radiation [46] and concurrent chemotherapy [47]. Detailed data regarding the toxicity of PCI have been limited.…”

L-myc polymorphism in cancer patients, healthy blood donors and elderly, tumor-free individuals in Russia

“…Although no functional differences between L and S variants have been noticed so far, there are data indicating a direct or indirect involvement of L-myc polymorphism in cancer predisposition and progression. For example, association of the L-myc genotype with tumor susceptibility has been described for nonHodgkin's lymphoma, hepatocellular carcinoma and sarcoma (Kato et al, 1990;Taylor et al, 1993;Crossen et al, 1994; Hsieh et al, 1996). L-myc allele distribution in more common cancer types has been described mainly in the context of its association with the metastatic spread of already existing neoplasia, whereas early reports provided no strong indications for its role in the predisposition to lung, colorectal, breast or other frequent tumors (reviewed by Vineis and Caporaso, 1991).…”