Lancet
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The original report of a possible association between myocardial infarction and the insertion/deletion (I/D) polymorphism of the gene for the angiotensin-1-converting enzyme (ACE) indicated a risk ratio for myocardial infarction with the DD genotype of 1.34 (95% CI 1.05-1.70), and the association was claimed to be particularly strong in a retrospectively defined low-risk subgroup (3.2 [95% CI 1.7-5.9). Subsequent investigations reached varying conclusions, but all were small, and much larger studies were needed. ⋯ This study involved many more cases than any previously reported study of this question, but did not confirm the existence of any substantial association. In an updated meta-analysis of these results with those of previously published studies, the risk ratio for myocardial infarction with the DD genotype seems to lie in the range 1.0 to about 1.1. Although an increase in risk of up to about 10-15% cannot be ruled out, substantially more extreme risks can be. Moreover, there are not especially strong associations in the subgroups previously selected for emphasis. These findings illustrate the need for some studies of candidate genes to involve much larger populations than is customary, without undue emphasis on retrospectively defined subgroups.
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Women with small mammographically detected breast cancers generally have good long-term outcomes, but a few with T1a (1-5 mm) and T1b (6-10 mm) tumours will eventually die from breast cancer. We investigated whether women at high risk of breast-cancer death could be identified with mammographic criteria and differentiated from women with small cancers of the breast and good outcomes. ⋯ Mammographic classification seemed to reliably predict good and bad long-term outcomes for survival in tumours of 14 mm or smaller, and especially for those smaller than 10 mm. The implications for therapy are substantial.