BACKGROUND Recently, we classified LINE-1 loci according to their methylation statuses and found that the percentage of hypomethylated LINE-1 loci ((u)C(u)C) can differentiate between the peripheral blood mononuclear cells (PBMCs) of oral cancer patients and normal controls with a higher specificity and sensitivity than overall methylation levels. Here, we evaluated the LINE-1 methylation levels and patterns in PBMCs from patients with cancers of the nasopharynx, lung, liver, bile duct, breast and colon. METHODS Combined Bisulfite Restriction Analysis (COBRA) of LINE-1 loci was performed to examine the LINE-1 methylation statuses of PBMCs from 216 cancer patients with 6 different types of cancer compared with 144 normal controls. RESULTS Only colorectal and nasopharyngeal cancer samples were found to have lower levels of overall LINE-1 methylation compared with normal controls (p<0.0001 and p=0.0022). However, %(u)C(u)C in cancers of the colon, liver, lung and nasopharynx was significantly higher compared with normal controls (p<0.0001, p<0.0001, p=0.01 and p=0.001, respectively). Furthermore, ROC curve analyses of these four cancer types also demonstrated the potential of %(u)C(u)C as a biomarker for cancer diagnosis. CONCLUSION Changes in the levels and patterns of genome-wide methylation of PBMCs are associated with cancer risk. For LINE-1, %(u)C(u)C is a more effective tumour marker for determining cancer risk than overall methylation levels.