Abbreviations: SIR = standardized incidence ratio; SMR = standardized mortality ratio; Obs = observed; Exp = expected. a Lung cancer. b Breast cancer. c Ovarian cancer. d Lymphoproliferative cancer. e Non-Hodgkin's lymphoma.

Table 6. Bradford-Hill's postulates [40]

1. Strength It measures the magnitude of association. In our example it is determined by SIR.

2. Consistency It responded by the question: has the association been repeatedly observed by different persons, in different places, circumstances and times?

3. Specificity If the association is limited to that cause and that effect. In other words: does the supposed cause only produce that effect? Here: is the malignancy only produced by autoimmune rheumatic diseases?

4. Temporality Evidence upon sequence in the presentation of events. Here: is the rheumatic disease diagnosed first and afterwards the malignancy?

5. Biological gradient Is the association related to a gradient dose-response? In other words: if more frequent the rheumatic disease is higher the probability of neoplasm?

6. Plausibility Is the association biologically plausible? This knowledge depends on the medical information of each day.

Here: can an autoimmune rheumatic disease produce a malignancy?

7. Coherence Interpretation of facts about association should not conflict with the facts known about the cause and effect.

So, does the association between rheumatic disease and malignancy conflict with the knowledge about the two entities?

8. Experiment Is there evidence of association derived from experimental studies such as clinical trials? Here: human experimental evidence is not ethically permissible.

9. Analogy Is there evidence of a similar association in the medical literature? Here, for example: other autoimmune diseases like thyroiditis can be associated with a high probability of developing a malignancy.

Table 7. Fulfilment of Bradford-Hill's [40] postulates in autoimmune rheumatic diseases and malignancy

Rheumatic Disease

Malignant neoplasm



Specificity Temporality

Biological gradient



Experiment Analogy

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