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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: What is the cause?

A recent Framingham Study, involving 1278 participants, has shown an inverse association between cancer and Alzheimer’s disease (1, 2). In other words, people who suffer from Alzheimer’s disease (AD) are likely to have a reduced risk of developing age-related cancers.

Quite remarkably, exactly the same type of inverse association exists in Down syndrome (DS). Thus, people suffering from DS, characterised by an extra chromosome 21 (trisomy 21, T21), have an increased risk of developing AD but, on the other hand, they have a decreased risk for the development of solid cancers (3). Furthermore, in vitro culture of DS brain stem cells provides a model for the development of the characteristic features of AD brains (4).

The outstanding question here is what might be the cause for this type of inverse association? This is an exceedingly important question, not the least as we here might find leads for the development of improved therapeutic measures for solid cancers as well as for Alzheimer’s disease (1-3).

Driver et al (1) suggest that the reason may be related to an inappropriate activation of the cell cycle. A related, intriguing, possibility is the occurrence of T21 mosaicism in the specific tissues. Thus, it has been suggested that the relative proportion of T21 cells are of importance. An increased proportion in the cerebral cortex would underlie the development of AD but, when occurring in the different relevant tissues, provide protection against development of solid cancers (3).

Hopefully, the recent support for research into the origin of AD (5) will lead to additional studies along these lines, thus promoting the development of improved therapy, not only for AD but also for solid cancers.

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

(3) Hultén MA, Jonasson J, Nordgren A, Iwarsson E. Germinal and Somatic Trisomy 21 Mosaicism: How Common is it, What are the Implications for Individual Carriers and How Does it Come About? Curr Genomics 2010, 6:409-19

(4) Shi Y, Kirwan P, Smith J, Maclean G, Orkin SH, Livesey FJ. A human stem cell model of early Alzheimer's disease pathology in down syndrome. Sci Transl Med. 2012, 4:124ra29

(5) Tanne JH: US scientists discuss early detection and treatment of Alzheimer's disease. BMJ 2012; 344:e1068

Competing interests: No competing interests

09 April 2012
Maj A Hulten
Medical Geneticist
Warwick University, Karolinska Institutet, Stockholm
22 Mayfield Road, Moseley, Birmingham B139HJ