Monday, February 02, 2009

Genetics Loads the Gun, Environment Pulls the Trigger

American Journal of Epidemiology 2009 169(2):219-226; doi:10.1093/aje/kwn353Cassandra E. Murcray, Juan Pablo Lewinger, and W. James Gauderman
Gene-Environment Interaction in Genome-Wide Association Studies


http://aje.oxfordjournals.org/cgi/content/abstract/169/2/219?etoc
Muin J. Khoury and Sholom Wacholder
Invited Commentary: From Genome-Wide Association Studies to Gene-Environment-Wide Interaction Studies--Challenges and Opportunities
Am. J. Epidemiol. 2009 169: 227-230; doi:10.1093/aje/kwn351.
http://aje.oxfordjournals.org/cgi/content/abstract/169/2/227?etoc
Nilanjan Chatterjee and Sholom Wacholder
Invited Commentary: Efficient Testing of Gene-Environment Interaction
Am. J. Epidemiol. 2009 169: 231-233; doi:10.1093/aje/kwn352.
http://aje.oxfordjournals.org/cgi/content/abstract/169/2/231?etoc
Cassandra E. Murcray, Juan Pablo Lewinger, and W. James Gauderman
Murcray et al. Respond to the Invited Commentaries
Am. J. Epidemiol. 2009 169: 234-235; doi:10.1093/aje/kwn349.
http://aje.oxfordjournals.org/cgi/content/full/169/2/234?etoc

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BrooklynDodger(s) Comments: This e-TOC links to some interesting full texts. Gene studies are the scientific equivalent of sex sells for getting funding. Way more rewarding than sampling for carcinogenic silica in a foundry basement.

Snarking aside, the Dodger(s) concede(s) that the new technology should be examined for its implications for a paradigm for high to low dose risk extrapolation. It's better to talk about "resistence" to carcinogens (or toxic chemicals with other endpoints) than "sensitivity." Stratifying human populations by genotype for studies of chemical exposure effects is nothing really new, we always calculate SMR's for men and women separately, a practice which improves sensitivity of a very insensitive method.

Greater variation in resistence to carcinogens in the human population suggests more shallow exposure response relationships and thus higher low does risk estimates than those observed in genetically homogeneous laboratory animal studies. The reviews in this issue of AJE suggest that not much has emerged. Maybe because these studies only examine genetic variation and not exposure variation, and because exposure assessments is weakened by not having identified many carcinogens, or recognized many identified carcinogens.

2 comments:

Mike said...

At our Super Bowl party, we ended up talking about the brain injuries former players have sustained. I wonder if there's a similar factor at play there. There's probably money in studying that too, but who is a good control group for NFL players?

BrooklynDodger said...

The evidence for brain injuries is at best anecdotal, prevalence of personality and neurological deficits not described. If it were true that rate was increased, might be an interaction of steroids and getting pounded in the head.

There was a mortality study of NFL requested by the NFLPA and conducted by NIOSH. It wasn't published.