50 whys to look for genes: 36. Ancestry might have medical significance

BRCA1 and BRCA2 mutations are more common in certain populations (e.g., people of Ashkenazi Jewish descent) than others.  Closer monitoring or prophylactic measures might be undertaken following positive tests (by genomic sequencing) for those mutations.  Genomic studies are identifying other genetic variants of biomedical significance that are more common in people of specific regions and thus of people whose ancestry traces to those regions (e.g., Genovese et al. 2010).  Even if no preventative measures are available, the tested individual and their doctors can more accurately assess risk for the particular biomedical condition once testing has been done.  (For example, instead of saying “breast cancer risk is slightly higher among Jewish women than among other women” (Komen site) presumably because of higher prevalence of BRCA1 and BRCA2 mutations, one can say to a woman of Ashkenazi Jewish descent that your risk is xx given that you do not have those mutations [where xx depends on age and family history].)


1. If preventative measures come with a cost, e.g., prophylactic ovary removal (oophorectomy), how does one give weight to the higher, but no means 100% risk?  The “regret factor” (i.e., what will I feel like if I didn’t take prophylactic action and I end up with cancer) can make risk into a black or white matter.

2. If monitoring comes with a cost, decisions get made about when the cost outweighs the benefit or, when the screening is done anyway, that may come at the cost fewer medical or public health resources being available for other modes of prevention (see series of posts on reactions to proposed changes in mammogram guidelines).

3. Because genetic testing is expensive, perceived race/ethnicity can be used as a proxy for possession of the genetic factor and thus shape treatment. Consider the following scenario:
Suppose you are a doctor seeing a patient with hypertension.  The patient is a 54 year-old black man.  What should you do?  What more do you want to know before deciding what to do?

Perhaps you already know more along the following lines:

Regardless of region, blacks were less likely than whites to achieve treatment success with atenolol (P = .02) or prazosin (P = .03) and more likely with diltiazem (P = .05).  ( Cushman et al., 2000)

(Atenolol is a beta blocker; prazosin lowers blood pressure by relaxing blood vessels ; diltiazem is a calcium channel blocker).

You might say to yourself, “I know that not all black men with hypertension do better with calcium channel blocker and worse with beta blockers, but on average they do.  So I’ll prescribe diltiazem and see what happens.  If it doesn’t work well, I’ll change the medication.”

Complications in this scenario are teased out in a previous post.

Cushman, W; D.J. Reda; H. M. Perry; D. Williams; M. Abdellatif; B. J. Materson, Regional and Racial Differences in Response to Antihypertensive Medication Use in a Randomized Controlled Trial of Men With Hypertension in the United States, Arch Intern Med. 2000;160:825-831.

Genovese, G. et al. (2010), Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans, Science 13 August 2010: 329 (5993), 841-845.

(Introduction to this series of posts)


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