Carrier State IS Disease State. Pre-Disease IS Disease.

In my ever-lasting challenge to Mendel, I submit my thesis. "There is no such thing as a carrier, nor is there such a thing as a single gene disorder."

Why? I have a treatise on the subject. But suffice it to say one thing. "No Gene Is An Island"

In the most recent argument I offer a study recently published in the Archives of Internal Medicine. Did you see the issue? It is a freakin' Gene Fest I tell ya. Too often we tell people you need 2 bad copies of Gene X to be affected by disease Y. But what if Gene X also caused Disease Z? Do the same rules apply? No wait a second, I thought Gene X only caused Disease Y? Well, we now know that many genes are invloved in diseases other than the traditional "Monogenic Disease" Which was reported ages ago, when we were limited to what we could taste, touch, smell, hear, see or feel.

This is the case with Marfan's disease. It is also the case in Cystic Fibrosis. Now a study from the Archives.

Researchers found that the genetic disorder, alpha-1 antitrypsin deficiency (α1ATD), could explain up to about 12 percent of lung cancer patients in this study and likely represents the same widespread risk in the general population. "This is a seriously underdiagnosed disorder and suggests that people who have lung cancer and chronic obstructive pulmonary diseases (COPD) in their families should be screened for these gene carriers," says Ping Yang, M.D., Ph.D., a Mayo Clinic epidemiologist and lead investigator on the study.

Don't you just love widespread, sweeping statements like the one from Dr Yang?

While true, yes the Sherpa did diagnose a 74 year old non-smoking white woman "COPD'er" with A delta 508 Cystic Fibrosis. It is not true that we should screen every 74 year old white woman with COPD for CF or α1ATD. But a careful detailed family history, should be sought out. Including environmental exposures...

In the case of Alpha 1 Antitrypsin Deficiency (α1ATD) much like CF, you need 2 defective genes to have "the Disease"....for now....

So what does this study say? From Medical News Today.

The α1ATD carrier rate among 1,443 genotyped patients with lung cancer was 13.4 percent, compared to 7.8 percent among unrelated control participants.All α1ATD gene carriers were at a similarly greater risk of developing lung cancer, regardless of smoking status. Those who had never smoked were at a 2.2-fold higher risk; light smokers had a twofold greater risk; and moderate to heavy smokers had a 2.3-fold increased risk.

Did they control for other environment or other genes? Yes.
This study actually paired cancer-free siblings with their α1ATD carrier brethern. Guess what? 2 fold increased risk of lung cancer. In CARRIERS!!!!
This serves as a modest control for environment and some modicum of epigenetic regulations.

So what we are saying is, that a previously "benign" carrier state...Is not so Benign! This is the same with CF carriers, Sickle Cell carriers, I could go on and on.

Ladies and Gentleman, I submit to you Exhibit C. Further proof that Mendel has been screwing up genetics and medicine for over a century. We must be careful in how we consult and counsel patients.

The Sherpa Says:
I have been called a blasphemer. But I do maintain, teaching Mendelian Genetics is a disservice to the medical community and to our undergraduate communities. It leads to be rigid in interpretation of things that are very much not black and white.