I can hardly share the passionate enthusiasm of Breuhahn et al. for the ''dramatic'' improvements in understanding of molecular pathogenesis of hepatocellular carcinoma (HCC) and the claim for ''further rationally designed clinical trials based on molecular evidence''. 1 Among the causes of HCC, they cite aflatoxins and hemochromatosis but failed, as too many do, to cite tobacco, which represents the cause of one-third of the cases. 2 Despite the success of the hepatitis B vaccine and the cure for hepatitis C, HCC remains a growing epidemic due to alcohol, tobacco, and processed foods (obesity and diabetes). 3 Here are the three agents of the modern epidemics.
Considering ''molecular evidence'', a PubMed search for ''geneexpression profiling'' and ''cancer'' provides more than 17,000 references since 1999. However, out of hundreds of biomarkers, KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is the only one integrated into clinical practice. It is limited to metastatic colorectal cancer, which constitutes half of all patients with colorectal cancer. Evidence was obtained in 2008 from a post hoc analysis of the CRYSTAL trial (study EMR 62202-013) with cetuximab, and the first trial designed with an intention-to-treat analysis, PRIME (study 20050203), has just been published. 4 The effect, although statistically significant, has very limited relevance: in wild-type KRAS, panitumumab-FOLFOX4 (infusional fluorouracil, leucovorin, and oxaliplatin) increases progression-free survival by 1.6 months compared with FOLFOX4 alone.
Medicine must avoid ''sciensationalism'' (sensationalism in science). 5 If more research is needed, it must be concerned with how to improve the implementation of evidence-based care and public policies against the leading avoidable causes of cancer worldwide: tobacco, alcohol, and obesity. A focus on molecular biology that ignores medical practice, interventional epidemiology, and social and political sciences will improve neither patient care nor prevention.