A case study of an interesting non-coding variant associated with indigenous American ancestry contributing to disparities in acute lymphoblastic leukemia risk.
My immediate thought is that this population the United States is repeatedly exposed to huge doses of pesticides over years, as they work in the fields, starting in childhood. And this is more prevelant amongst those with indigenous ancestry as they are the most likely to be impoverished enough to need to work in the fields. And I speak as someone from a family of farmworkers. My Grandmother worked from age 6 to 18 in the fields. Her children didn't have to. Some never make it out.
To be honest, I have not looked very closely at environmental exposures in relation to leukemia in children. My prior is that early onset cancers require potent genetic insults that are often beyond most types of environmental exposures.
For carcinogenic exposures, dose and duration are important factors to triggering cancer. For instance, I think the typical exposure for increased smoking-related lung cancer risk is like 20+ pack-years.
Of course, tracking down all the causes is ideal. My default is that we can usually do this more reliable with genetic research because the tools are powerful and findings can contribute to drug discovery.
It is also worth noting that this increased risk is being found in American residents with indigenous American ancestry. The study was conducted on a Californian cohort.
I don't know if you've read about the incidence of CKD in El Salvador but that seems to be the disease case more linked to exposures like pesticides due to its prevalence in farm laborers. However, even in that cases there's been a long-run epidemiological debate about the different causes. There's some smoke there but it's hard to pin down.
Now that I think about that, you're right, you're talking about children, not adults with decades of exposure.
When I was in college in the 1990s in California the farmworker labor activists claimed pesticide exposure to the workers was causing high incidences of births of children without limbs or limb deformities - complete with heartbreaking photo art projects. But that's a different mechanism at play than leukemia.
Now that I've gotten all my wild ideas out, I can focus on what you actually wrote. Thank you. :)
A stupid question, if you don't mind - does "1.3-fold" this mean 30% higher or 130%? (2 fold is doubling, so 1.3 fold is 30%?)
and also, does the paper go into whether IKZF1 could have originated in Asia and then come over with the earliest migrants to the the Americas? Was the evidence for selection rather than founder effect/bottleneck?
The incidence is 30% higher. The age-adjusted incidence rate for Hispanic kids is ~6 per 100,000 while the general population rate is between 3-5 per 100000.
The authors argue that the variant arose after the European-Asian split but before the Asian-Indigenous American split. The study doesn't sample Asian population too well and the relevant variant is at a some high allele frequency (17%) in the available data. However, in East Asians the variant doesn't occur in concert with the GWAS risk signal at the promoter. Since these regions physically interact it is possible both play a role in the Hispanic/Latino specific risk.
The authors argue their constructed genealogy and the enriched frequency of the variant in IAM is a selection signal not present in European or Asian populations. I haven't evaluated their analysis closely on the selection claim so it is possible there are other explanations like the founding migration or drift.
My immediate thought is that this population the United States is repeatedly exposed to huge doses of pesticides over years, as they work in the fields, starting in childhood. And this is more prevelant amongst those with indigenous ancestry as they are the most likely to be impoverished enough to need to work in the fields. And I speak as someone from a family of farmworkers. My Grandmother worked from age 6 to 18 in the fields. Her children didn't have to. Some never make it out.
To be honest, I have not looked very closely at environmental exposures in relation to leukemia in children. My prior is that early onset cancers require potent genetic insults that are often beyond most types of environmental exposures.
For carcinogenic exposures, dose and duration are important factors to triggering cancer. For instance, I think the typical exposure for increased smoking-related lung cancer risk is like 20+ pack-years.
Of course, tracking down all the causes is ideal. My default is that we can usually do this more reliable with genetic research because the tools are powerful and findings can contribute to drug discovery.
It is also worth noting that this increased risk is being found in American residents with indigenous American ancestry. The study was conducted on a Californian cohort.
I don't know if you've read about the incidence of CKD in El Salvador but that seems to be the disease case more linked to exposures like pesticides due to its prevalence in farm laborers. However, even in that cases there's been a long-run epidemiological debate about the different causes. There's some smoke there but it's hard to pin down.
Thanks for sharing your experience!
Now that I think about that, you're right, you're talking about children, not adults with decades of exposure.
When I was in college in the 1990s in California the farmworker labor activists claimed pesticide exposure to the workers was causing high incidences of births of children without limbs or limb deformities - complete with heartbreaking photo art projects. But that's a different mechanism at play than leukemia.
Now that I've gotten all my wild ideas out, I can focus on what you actually wrote. Thank you. :)
A stupid question, if you don't mind - does "1.3-fold" this mean 30% higher or 130%? (2 fold is doubling, so 1.3 fold is 30%?)
and also, does the paper go into whether IKZF1 could have originated in Asia and then come over with the earliest migrants to the the Americas? Was the evidence for selection rather than founder effect/bottleneck?
The incidence is 30% higher. The age-adjusted incidence rate for Hispanic kids is ~6 per 100,000 while the general population rate is between 3-5 per 100000.
The authors argue that the variant arose after the European-Asian split but before the Asian-Indigenous American split. The study doesn't sample Asian population too well and the relevant variant is at a some high allele frequency (17%) in the available data. However, in East Asians the variant doesn't occur in concert with the GWAS risk signal at the promoter. Since these regions physically interact it is possible both play a role in the Hispanic/Latino specific risk.
The authors argue their constructed genealogy and the enriched frequency of the variant in IAM is a selection signal not present in European or Asian populations. I haven't evaluated their analysis closely on the selection claim so it is possible there are other explanations like the founding migration or drift.