Common gene polymorphisms, cancer progression and prognosis

Neoplastic growth was often regarded as an autonomous process driven by uncontrolled expansion of malignant cell population. This view is now being transformed as it becomes apparent that basically normal regulatory and metabolic mechanisms comprising subcellular processes as well as homo- and heterotypic cell interactions are extensively used by growing tumours throughout all stages of their development. Therefore the role of normal genetic variation emerges as a major factor determining different aspects of neoplastic growth and eventually outcome of the disease. This review is focused on polymorphisms in the genes encoding products acting at post-initiation stages of tumour development. Its four main sections are devoted to gene polymorphisms affecting: (i) growth control at the cellular level (cell proliferation, differentiation and death); (ii) factors involved in tumour invasion and metastasis (immune and inflammatory responses, extracellular matrix remodelling, angiogenesis and cell adhesion); (iii) action of hormones and vitamines on growing tumours; (iv) outcome of cancer therapy (cancer pharmacogenetics). Although active research in this field has been started only recently, some directions (e.g. cancer pharmacogenetics) already demonstrate impressive achievements. At the same time the reliability of results reported by many groups remains questionable mostly due to insufficient statistical power of the studies and often random choice of polymorphisms. It is evident that large studies based upon combined analysis of groups of genes within relevant regulatory and metabolic pathways have a much higher potential value in terms of unravelling prognostically important individual polymorphism profiles. (C) 2004 Elsevier Ireland Ltd. All rights reserved.