Background: Epidemiologic and molecular studies report inverse, shared, and context-dependent associations between amyotrophic lateral sclerosis (ALS) and cancer. We evaluated population estimates, causal-genetic evidence, cross-disease transcriptomic patterns, model robustness, and patient-level transport. Methods: We integrated four published all-cancer estimates, a targeted Mendelianrandomization (MR) and phenome-wide evidence refresh, eleven public expression cohorts, covariateadjusted differential expression, sample-label permutation, gene-set analyses, nine machine-learning families with five fixed variants each, native MOFA+/SOFA and scVI/totalVI/MultiVI analyses, a 40-donor ALS cohort analyzed as donor-summed RNA-count pseudobulks with voom-limma precision weights to account for mean-variance dependence, and a five-patient paired lung-cancer positive control. Results: The mixed-time-origin population synthesis gave a Paule-Mandel ratio of 0.939 (modified Hartung-Knapp 95% CI 0.687-1.282; I 2 = 66.1%); the strict post-index estimate was 0.998 (95% CI 0.609-1.634). Published overall-cancer MR gave an odds ratio of 1.01 (95% CI 0.94-1.09). The nominal European discovery colorectal association, 0.84 (0.74-0.96), did not replicate: the larger European panel gave 0.99 (0.93-1.06) and the combined estimate was 0.92 (0.79-1.09). A five-instrument East Asian analysis gave 0.32 (0.15-0.69; P = 0.004), requiring independent replication. The four ALS-cancer gene correlations had permutation-adjusted q ≥ 0.262; fifteen ALS pathways replicated by rank enrichment. Graph neural networks (GNNs) ranked highest in the expanded gene-level benchmark (median AUC 0.645; five-variant range 0.638-0.649), versus approximately 0.54-0.61 across the other eight family medians. In 40 independent donors, the locked 103-gene score had AUC 0.604 (95% bootstrap CI 0.418-0.777; permutation P = 0.133), with acquisition-block AUCs of 0.273-0.290 and leave-one-donor-out AUCs of 0.348-0.414. Five classical lung-cancer classifiers ranked tumor above matched normal in all five held-out patients (exact P = 0.03125); the ALS-cancer score increased in three patients and decreased in two (P = 0.406). Conclusions: Population and overall-cancer genetic estimates centered near 1. Colorectal findings did not establish a replicated, general protective association. Molecular associations varied by tissue and ALS subtype. The GNN advantage concerned gene-level discrimination, not validated patient-level diagnosis or cancer-risk prediction.