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Background: Establishing causal relationships is essential in biology and medicine. However, various notions of causality have been operationalized at different times in various fields of the life and health sciences. While this is expected from a history or sociology of science point of view, as different accounts may correspond to what is valued in terms of establishing causal relationship at different times as well as in different fields of biology and medicine, this may come as a surprise for a present-day actor in those fields. If, over time, causal accounts have not been fully dismissed, then they are likely to invite to some form of, potentially salutary, explanatory pluralism. Summary: In the decades following WWII, psychosomatic medicine could propose that psychological factors cause somatic diseases. But today, most of medicine has to meet the standard of a randomized clinical trial before any causal relationship can be proposed. Instead, in biology, mechanisms seem to be the most-valued causal discourse to explain how phenomena of interest are brought about. Here, the focus will be on how psychoneuroimmunology, an interdisciplinary research field addressing interactions between the nervous system and immune system, and between behavior and health, has considered causal relationships between psychological factors and cancer. Key Messages: When it comes to causal explanations of links between psychological factors and cancer, psychoneuroimmunology is invited to consider the question of the directionality of these links as well as what and how factors causally contribute to cancer.

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