Summary Some studies have suggested that the S allele of the MYCL oncogene, which results from an intragenic EcoRI restriction fragment length polymorphism (RFLP), may be associated with cancer susceptibility. In addition, this allele has also been linked to metastases and adverse survival in certain cancers, although studies of lung cancer patients from different populations have yielded controversial results. We studied 108 cases of surgical resected non-small-cell lung cancer (NSCLC) and found no evidence that MYCL gentotypes were associated with tumour progression or a worse prognosis. However, the presence of loss of heterozygosity (LOH) In terms of cancer susceptibility, the S allele of MYCL was more common in patients with non-Hodgkin's lymphoma (Crossen et al., 1994), and male patients with bone and softtissue sarcomas . In addition, the SS genotype was more frequent in colorectal cancer patients than in young blood donor controls (Young et al., 1994). However, the cancer-susceptibility model is controversial, as the SS genotype appears to protect against hepatocellular cancer (Taylor et al., 1993), and the S allele was not increased in patients with lung cancer (Tamai et al., 1990;Weston et al., 1992Weston et al., , 1994, breast cancer (Champeme et al., 1992) or lymphoma/leukaemia (Chenevix-Trench et al., 1989).As regards tumour progression, Kawashima et al. (1988, 1992), in an initial study followed by a larger study involving 252 Japanese lung cancer patients, showed that the S allele predisposed to metastases and adverse prognosis. Conversely, this association has not been found in Caucasian (Norwegian and North American) lung cancer populations (Tamai et al., 1990;Tefre et al., 1990;Weston et al., 1992Weston et al., , 1994. While the conflicting results may have been owing to racial/ethnic differences, there were also significant methodological variations between the studies, such as case stratification, including heterogeneity in the subtypes of lung cancer, disease stage and treatment modalities; all factors which are known to affect tumour progression and outcome.To address some of these possible confounders, we investigated the relationship of MYCL genotypes to tumour stage, nodal metastases and survival in a well-defined, homogeneous lung cancer subset; histologically diagnosed NSCLC patients who had curative surgery as their primary treatment and who had. comprehensive post-surgical staging and follow-up.
Materials and methodsDNA was obtained from 108 cases of post-surgically staged, resected NSCLC and normal lung tissue from patients at The Prince Charles Hospital, Brisbane, Australia as previously described (Fong et al., 1995).The MYCL gene was discovered as two additional DNA fragments of 10.0 kb and 6.6 kb when the MYC gene was used to probe EcoRI digested human genomic DNA (Nau et al., 1985). These fragments represent a RFLP at the MYCL locus, situated in the second intron (Kaye et al., 1988). This RFLP can also be revealed with polymerase chain reaction (PCR) using primers, which fla...