<img loading="lazy" decoding="async" class="alignright size-full wp-image-2564" title="cancer_microscope" src="https://blog-api.23andme.com/wp-content/uploads/2009/01/cancer_microscope.jpg" alt="" width="350" height="222" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/01/cancer_microscope.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/01/cancer_microscope-300x190.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
Each type of cancer has its own idiosyncrasies, but when it comes down to it, they all have one thing in common: failure to control cellular growth. So it’s somewhat surprising that when genome-wide association studies have looked for single common variations associated with the risks for multiple types of cancer, they have for the most part identified only SNPs that are peculiar to just one form of the disease.
A new study published online Sunday in <a href="https://dx.doi.org/10.1038/ng.296" target="_blank" rel="noopener">Nature Genetics</a> may signal a change in this trend. A team of researchers led by Thorunn Rafnar and Patrick Sulem of deCODE Genetics in Iceland describes how a genetic variation they originally found to be associated with the risk for developing basal cell carcinoma (BCC), a type of skin cancer, is also linked to increased odds for four other cancers.
In a study of more than 33,800 cancer patients and 45,800 controls, the scientists found that a variant associated with increased odds of lung, bladder, prostate and cervical cancer, in addition to the previously found association with BCC. This variation decreases the odds of cutaneous melanoma, another type of skin cancer.
The variant was also marginally, although not significantly, associated with increased odds of endometrial cancer and decreased odds of colorectal cancer.
There was no association of the SNP with cancer of the breast, kidney, stomach, thyroid, ovary or pancreas, nor with lymphoma, multiple myeloma or squamous cell carcinoma (a third type of skin cancer). The authors say that further investigation in even larger samples will be needed to determine if there truly is no association, or if they just haven’t picked it up yet.
An association was also found between a nearby variant and four of the five cancers that were associated with it.
Both SNPs are near a gene involved in maintaining the protective stretches of DNA attached to the ends of chromosomes called telomeres. The authors suggest that these SNPs, or other nearby variations, may lead to shortened telomeres, which are associated with several types of cancer.
Telomere length is determined in part by genetics, but environmental factors such as smoking and radiation can also shorten them. The authors note “four of the five cancers associated with the risk variants are cancer types that have strong environmental contributions to risk — smoking and occupational exposures for lung and bladder cancer, UV irradiation for BCC and infection with human papillomavirus for cervical cancer.” More research could help explain the exact relationship between the genetic variations found in this study and the environmental causes of these cancers.

23andMe Blog

23andMe Blog Team

One Variation, Many Cancers

Many cancer patients who receive high doses of chemotherapy or radiation undergo a bone marrow transplant to replace blood cell-generating tissues that are killed as part of their treatment. But after a transplant these patients face a new challenge — opportunistic infections that take advantage of their weakened immune systems.
<img loading="lazy" decoding="async" class="right" title="aspergillus" src="https://blog-api.23andme.com/wp-content/uploads/2008/06/aspergillus.gif" alt="Aspergillus" width="208" height="207" />Aspergillus fumigatus
One common and life-threatening infection among bone marrow transplant patients is invasive aspergillosis (IA), which is caused by the fungus Aspergillus fumigatus. About 10% of bone marrow transplant recipients are affected by invasive aspergillosis (IA). An estimated 30% of those affected will die within three months.
A study published in the June issue of <a href="http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000101">PLoS Genetics</a> shows that a SNP in the gene encoding a protein called plasminogen significantly affects the risk of developing IA after a bone marrow transplant. Compared to transplant patients with the GG genotype at rs4252125, the risk of developing IA was increased 3.0 fold in people with the AG genotype, and 5.6 fold for people with the AA genotype.

Zaas et al began their study of IA in bone marrow transplant patients by looking for clues in several genetically distinct strains of mice. The researchers mimicked a bone marrow transplant in the mice by giving them drugs that suppressed their immune systems. They then exposed the animals to the Aspergillus fungus.
The researchers found that some mouse strains survived Aspergillus infection, while others did not. A SNP in the plasminogen gene correlated with Aspergillus susceptibility, and the researchers considered it a likely candidate because other scientists had recently indicated that proteins in the same biological pathway as plasminogen are important for fighting off infectious pathogens.
Armed with this clue from mice, Zaas et al turned their attention to humans. They followed a group of 230 immunosuppressed bone marrow transplant recipients for one year. Just as they had seen in the mice, the researchers found that IA was associated with a SNP (rs4252125) in the plasminogen gene.
Oddly, the association between rs4252125 and IA applies only 40 days or more post-transplant. The authors aren’t exactly sure why this is the case. It could be due to the low proportion of patients who are infected with Aspergillus in the first 40 days after their transplants. It could also be that until 40 days, when the transplanted bone marrow really starts to take hold, other risk factors swamp out the effect of rs4252125.
Laboratory tests showed that the plasminogen protein encoded by rs4252125, which is made in the liver, binds to Aspergillus fungus. And computer models indicate that the SNPs found in both mice and humans change the protein in a way that alters binding to the fungus, giving a possible explanation for why the SNP affects susceptibility to IA.
Though more research and evaluation is required before clinical applications can be developed based on this research, the authors write in the conclusion of their report that their results have “important implications for pre and post transplant care, and may also have implications for the management of other immune-compromised patients. For example, genetic testing could identify high risk individuals who may benefit from use of broad-spectrum antifungal agents or enhanced monitoring for infection.”

Genetics and Risk for Infection After Bone Marrow Transplant

<img decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2008/05/cocktail.jpg" alt="cocktail.jpg" class="right alignright">A new study in <a href="https://dx.doi.org/10.1038/ng.151" target="_blank" rel="noopener noreferrer">Nature Genetics</a> shows that the increased risk of developing cancer in the mouth, throat, voice box and esophagus due to drinking is partially offset by the rarer versions of two SNPs associated with alcohol metabolism.
Cancers of the oral cavity, throat (also called the pharynx), voice box (or larynx) and esophagus are collectively known as upper aerodigestive (UAD) cancers. <a href="http://findarticles.com/p/articles/mi_m0CXH/is_3_29/ai_n21041723/pg_1" target="_blank" rel="noopener noreferrer">Alcohol consumption</a> is known to be a significant risk factor for these cancers. Studies have shown that the areas of the body that come into closest contact with ingested alcohol are at highest risk of being affected by cancer.

The two SNPs associated with UAD cancers are both located in genes that are part of the alcohol dehydrogenase (ADH) enzyme pathway, a group of proteins that aids the body in metabolizing alcohol. The authors of the study hypothesize that the protective versions of the SNPs they found exert their effect on UAD cancers by changing the carcinogenic effects of alcoholic beverages. These SNPs had no effect among non-drinkers.
Hasibe et al studied six SNPs in ADH pathway genes in a total of 3,876 people with UAD cancers and 5,278 healthy controls, in hopes of finding DNA variants associated with these diseases. This large study group was comprised of three smaller study groups: one group from eastern Europe with 809 patients and 2,586 controls; one group from western Europe with 1,356 patients and 1,407 controls; and a final group from Latin America with 1,711 patients and 1,285 controls.
Both rs1229984 and rs1573496 were significantly associated with UAD cancers in the large study group and each of the smaller study groups individually.
When the researchers broke the patients into groups based on specific cancer type — oral/throat, voice box, and esophagus — they found that both SNPs impacted the risk of developing the subtypes of cancer to different extents (see the chart at the end of this post for details).
About 19 out of every 100,000 people is diagnosed with UAD cancer per year in the United States. Individually, the lifetime risks of developing these cancers are: oral/throat, 1 in 99; voice box, 1 in 274; and esophagus, 1 in 198.
Those who have one or two copies of the T version of rs1229984 were found to have 0.56 times the odds of developing UAD cancer compared to those with two C versions. For those who carry one or two copies of the G version of rs1573496, their odds of developing UAD cancer were 0.68 times those with two C versions. People who carry at least one T at rs1229984 and one G at rs1573496 were found to have 0.45 times the odds of developing UAD cancer compared to people who had no protective versions of either SNP.
The authors say that the exact mechanism by which the protective versions of these two SNPs are working is not clear. It is known that people with one or two copies of the T version of rs1229984 metabolize ethanol up to 100 times faster than people with two copies of the C version. The authors of this study speculate that this faster metabolism may protect tissues by reducing their exposure to the effects of alcohol.
The tables below sum up the results of this study. The “effect” of each SNP is the change in odds for carrying either one or two copies of the protective version.
<img decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2008/05/booze2.jpg" alt="booze2.jpg">

cancer — Page 3

One Variation, Many Cancers

Genetics and Risk for Infection After Bone Marrow Transplant

Alcohol Metabolism SNPs are Associated with a Decreased Risk for Cancer, but Only in Drinkers

Stay in the know.