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Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study

BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e1442 (Published 12 March 2012) Cite this as: BMJ 2012;344:e1442

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Re: Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study

Inverse association between cancer and Alzheimer’s disease (AD). But, for all cancer types?

A recent Framingham study involving 1278 participants has shown an inverse association between cancer and AD (1,2). In other words, people who suffer from AD are likely to have reduced risk of develop age related cancer.
Driver et al correctly acknowledge that further insight will possibly be gained from analysis in large clinical database with the power to look at the relation between AD and individual types of cancer .
In particular, data reported in Table 5 showed a similar incidence between AD subjects and controls for colorectal tumors (2.0 vs 2.6%), whereas the incidence of other main tumors, namely lung, was 1/3 in AD patients 0.6 vs 2.2%; on the contrary, bladder and urinary cancer showed an increased incidence in AD patients vs controls (1.4 % vs 0.9 %)
Interestingly, in a completely different study, a cross-sectional survey of the prevalence of associated cancer among 1392 subjects, admitted with a diagnosis of AD to a geriatric institute during years 2004-2009, an overall diagnosis of previous of subsequent cancer, was made in 79 subjects (51 F, 28 M, mean age 83 years, range 62-97 y). Interestingly, in comparison with 25 breast and 15 colorectal cancers, in patients with AD there where only two cases of lung cancer, 0 with pancreas, or kidney cancer, whereas there were 6 patients with bladder and the urinary tract cancer (double that in the control population). Therefore, the results of two different approaches, which can be considered complementary and mutually supportive of each other, seem to suggest that the occurrence of most, but not all cancer types, is likely reduced in subjects with AD.
In our opinion, the striking similarity of AD associated cancers, which are not only less (less the 1/3 in our study) and then different in numbers, but also different for type (in particular they involve mainly some histotypes, and not others, with an increased incidence for some cancer sites) cannot be considered fortuitous. Obviously, the Driver’s study should be replicated by other longitudinal studies, maybe including a greater number of incident cases. But this will require long time.
Exploring possible causes of the inverse association, we suspect that, instead of a presumed cooperation (or mutually exclusion) concerning only a few genes (p53, PIN1), acting along the same molecular pathway, a more complex genetic signature, - including many genes, and also epigenetic and/or environmental factors (smoke can be one of these factors), maybe involving major complex functions, such as immune response or cancer susceptibility, - could facilitate, at the entire organism level, the mutually exclusive occurrence of AD and cancer, irrespective of the prior occurrence of cancer or AD. The observation that, whereas some of the most frequent cancer types are greatly reduced, other histotypes (bladder and urinary tract) are increased, suggests that further study is required, focusing selectively not only on cancer prevalence and incidence, but also on the inhomogeneous incidence of the various cancer types and sites.

References
(1) Driver JA, Beiser A, Au R, Kreger BE, Splansky GL, Kurth T, Kiel DP, Lu KP, Seshadri S, Wolf PA. Inverse association between cancer and Alzheimer's disease: results from the Framingham Heart Study. BMJ 2012;344:e1442
(2) Gouguli M. A reduced risk of Alzheimer’s disease in those who survive cancer. BMJ 2012; 344:e1662

Competing interests: No competing interests

19 April 2012
Francesco Cetta
Oncologistic Surgeon
Valentina Guercio, Cinzia Negri Chinaglia, Massimo Monti
IRCCS Multimedica
Milano, Italy