Colorectal cancer is the third most common cancer (excluding skin cancers) and the second leading cause of cancer-related deaths in the United States. Each year about 150,000 people are diagnosed with the disease.

Risk factors for colorectal cancer include age (most cases occur in people over 50), ethnicity (African Americans and Ashkenazi Jews have particularly high rates of the disease), a personal history of colon polyps or colorectal cancer, and the presence of inflammatory bowel disease (Crohn’s disease or ulcerative colitis).  Obesity, physical inactivity, smoking and heavy drinking have also all been associated with increased risk for colorectal cancer.

Genetics contribute to a person’s colorectal cancer risk, although non-genetic factors seem to play a larger role.  About 5% of people with colorectal cancer, however, develop the disease as a result of either familial adenomatous polyposis (FAP) or Lynch syndrome, two cancer syndromes caused by serious genetic mutations.

Anyone with a family history of colorectal cancer should talk to their health care professional about what screening procedures, and possibly what genetic tests, are right for them.

Research to find common genetic variants associated with colorectal cancer risk has yielded several good associations, but together they explain only a small part of the genetic contribution to the disease. There are probably many more variants with small effects left to be found, as well as rare variants with larger effects.  23andMe customers can see their results for three replicated SNP associations in the Colorectal Cancer Research Report.  Spittoon posts addressing colorectal cancer can be found here, here, here and here.

Learn More About Your Risk

Several online tools are available to help you get a better idea of your risk for colorectal cancer.

• National Cancer Institute
• Washington University School of Medicine Siteman Cancer Center
• My Family Health Portrait – a free online tool provided by the Surgeon General that can help you assemble your family’s health history

Get Involved

You can contact the following organizations to learn more about colorectal cancer and find out how to get involved in Colorectal Cancer Awareness Month.

• Colon Cancer Alliance
• American Cancer Society

And for those who want an up-close lesson about colorectal cancer, click here to see if the Prevent Cancer Super Colon™ is coming to a town near you.

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Colorectal cancer is the third most commonly diagnosed cancer in the U.S., and the third leading cause of cancer death.  In 2008 close to 50,000 people succumbed to the disease.

But not all groups are affected equally.  An American Cancer Society study found that colorectal cancer incidence rates are more than 20% higher for African Americans than Caucasians. Death rates from the disease are 45% higher.

Lifestyle factors, access to healthcare and cultural differences have all been proposed as reasons to explain the racial disparities in colorectal cancer survival. But new research from the University of Alabama, published today in the journal Clinical Cancer Research, shows that for some African Americans, genetics may play a part too.

Researchers analyzed 373 colorectal tumors – 137 taken from African Americans and 236 taken from non-Hispanic Caucasians.  They found that African American patients with two Gs at rs1042522 in the p53 gene were 2.15 times more likely to die of colorectal cancer than those with one or no copies of a G at this SNP.  In Caucasians there was no association between survival and rs1042522.

Seventeen percent of African American patients had two Gs, while only 7% of Caucasian patients did.

(23andMe customers can check their data for rs1042522 using the Browse Raw Data feature.)

The p53 gene encodes a tumor suppressor protein that protects against cancer, in part, by telling damaged cells to self-destruct instead of turning into tumors.  Mutations in the p53 gene that disrupt its function are a common feature of many cancers. (These mutations are distinct from the rs1042522 variation.)

Although the findings will need to be replicated in larger studies, the study’s authors suggest that rs1042522 might be a race-specific prognostic marker for African American patients with colorectal cancers and that someday analysis of this SNP might aid in designing optimal treatment regimens.

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Our SNPwatch posts here at The Spittoon are one of our most exciting features. They give our customers the opportunity to connect their genetic data to the newest discoveries, often within just hours of a study’s publication.

Looking ahead to 2009, we can only begin to imagine the exciting discoveries that will be made in genetics. In the meantime, here are a few of our favorite SNPwatches from 2008:

SNPs That Affect Drug Response
We reported on several studies this year that showed the importance of genetic variations in determining how different people react to certain medications.

• A report in Nature Genetics showed that some women with a particular version of a SNP in the NQO1 are less likely to survive breast cancer after treatment with the commonly used chemotherapeutic epirubicin.
• A study by the SEARCH Collaborative Group found that a version of one SNP is associated with an increased risk for myopathy (muscle pain and/or weakness) in people taking cholesterol-lowering drugs called statins.
• Mayo clinic researchers found that the weight loss drug sibutramine (Meridia) is effective only in people with specific versions of three different genes.
• And just this month we brought you news of three studies that showed that a genetic variant known to affect the metabolism of the anti-clotting drug clopidogrel (Plavix) also affects heart attack patients’ risk of a second major cardiovascular event.

Shared SNPs
Sometimes multiple conditions strike the same person or run in families. Several studies published this year showed that shared genetic risk factors may be part of the reason why.

• Obesity is a known risk factor for many cancers. Researchers found that a variant of adiponectin, a hormone released by fat cells, can increase the risk of developing colorectal cancer.
• Other researchers found variants that affect the risk of developing both type 1 diabetes and celiac disease, two autoimmune diseases that tend to cluster together. One of these shared variants is also associated with HIV resistance.
• Finally, a report published this month in the Proceedings of the National Academy of Sciences showed that a single genetic variant can make a person prone to greater indulgence in both smoking and drinking.

SNPs Associated with Risk Factors for Disease
Several studies this year looked beyond disease itself and instead found associations between SNPs and traits known to be risk factors for disease.

• One study found an association between several SNPs and fasting plasma glucose, a measure of how well a person’s body can control blood sugar levels – a process that goes awry in diabetes.
• Another research group reported SNPs associated with glycated hemoglobin levels, a measure of long-term blood sugar control and another factor associated with the risk of developing diabetes.
• The findings of three papers published in Nature Genetics roughly doubled the number of SNPs associated with blood levels of cholesterol and triglycerides, important risk factors for cardiovascular disease.
• And finally, in a study that looked at behavior instead of metabolic markers, researchers found that a variant in the FTO gene known to increase the risk for obesity affects food choices in children, pushing them towards foods denser in calories.

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The connection between obesity and cancer is well established. As many as 25 to 30 percent of several major cancers – colon, breast (postmenopausal), endometrial, kidney, and esophagus – may be accounted for by obesity and physical inactivity. Some studies have also found links between obesity and cancers of the gallbladder, ovaries, and pancreas.

It is not yet clear to scientists, however, how obesity increases the risk for certain cancers. Part of the answer may lie in a hormone released by fat cells — adiponectin. Decreased blood levels of this hormone, which are found in obese people, have been linked with breast, endometrial, prostate and colon cancer.

A new study published today in the Journal of the American Medical Association provides further evidence for adiponectin being the link between obesity and cancer. Researchers have demonstrated that a variant in the gene that encodes the hormone influences the risk of developing colorectal cancer.

Kaklamani et al examined several SNPs in the adiponectin and adiponectin receptor genes in a total of 629 people with colorectal cancer and 855 people without the disease. All subjects except for 37 cases and 37 controls were of European ancestry. The researchers found that people with one or two Gs at rs266729 in the adiponectin gene had 27% lower odds of developing colorectal cancer compared to those with two Cs.

(23andMe customers can look up their data for rs266729 using the Browse Raw Data feature)

According to the report’s senior author, Dr. Boris Pasche, these research findings could help identify people who would benefit from increased colorectal cancer screening.

“Our hope is that we can significantly improve the screening and early detection for this disease, and open new avenues for better understanding the genetic and lifestyle factors that influence colon cancer risk, “ he said in a statement.

Pasche went on to caution that additional studies are needed to confirm whether those without the adiponectin variant that appears to protect people from colorectal cancer will benefit from cancer-prevention lifestyle changes such as diet and exercise.

A different variant in the adiponectin gene was recently identified as a modifier of breast cancer risk in a study co-authored by Pasche. Understanding how variants in this gene influence breast and colorectal cancer risk, and whether the variants affect the risk for other cancers, will require more research.

Colorectal cancer is the second-leading cancer killer of Americans. According to estimates from the American Cancer Society, 149,000 people will be diagnosed with the disease and 50,00 will die this year alone.

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Three studies published Monday in Nature Genetics report new associations between SNPs and common diseases. Two of the studies find new SNP associations for colorectal cancer, while the third addresses Type 2 Diabetes.

All three studies relied upon very large sample sizes, which increased the chances that the researchers would find SNPs that individually have a very modest effect on the risk of disease, but in the right combinations may greatly increase the odds a person would be affected.

Colorectal Cancer
Colorectal cancer is the third most common cancer (excluding skin cancers) and the second leading cause of cancer-related deaths in the United States. The average lifetime risk of developing colorectal cancer is about 5% in Western European and North American populations.

In Tomlinson et al, researchers from several large consortiums used a multi-phase approach to narrow in on SNPs significantly associated with colorectal cancer. Using three phases that examined about 18,800 people with colorectal cancer and 18,400 controls (all of European ancestry) the scientists identified two new SNPs associated with colorectal cancer – rs10795668 and rs16892766.

When the researchers split the individuals with colorectal cancer into more specific groups, they found some evidence that the riskier version of rs10795668 increased the odds of developing rectal cancer more compared to the odds of developing colon cancer. The effect of rs16892766 was significantly stronger in cases of colorectal cancer that arose before the age of 60.

The second study, by Tenesa et al, also took a multi-phase approach for finding SNPs associated with colorectal cancer. In four phases of testing that examined about 17,500 people with colorectal cancer and 16,400 controls (all of European ancestry except for one group from Japan) they found one new SNP associated with colorectal cancer and replicated two other associations that had been found in previous studies.

In people with European ancestry, the C version of SNP rs3802842 increased the odds of colorectal cancer. In the Japanese population, however, the SNP was not significantly related to the odds of developing colorectal cancer.

But if the researchers took into account whether a patient had rectal or colon cancer (instead of combining the two types of cancer into one category), they found that the C version of rs3802842 did increase the risk for developing rectal cancer in the Japanese population.

The A version rs7014346 and the C version rs4939827 were also found to be associated with an increased risk for colorectal cancer. These two SNPs had been found in previous studies. The riskier versions of both of these SNPs increased the risk for colorectal cancer in both the Japanese and European populations.

Tenesa et al calculated that a person with two copies of the riskier version for each of the three SNPs (rs3802842, rs7014346, and rs4939827) – a situation only expected to happen in 0.5% of the population – would have 2.6 times the odds of developing colorectal cancer as someone with two copies of the less risky version at all three SNPS.

Summary of New Colorectal Cancer Data:
23andMe customers can check out their data at each of the SNPs newly associated with colorectal cancer in the Genome Explorer (now called Browse Raw Data).

In the chart below, each SNP’s rsid number is followed by the version of the SNP that is less prevalent in the population. The two columns labeled “effect” show the change in odds for developing colorectal cancer when either one or two copies of the less prevalent version of the SNP are present compared with the odds of developing the disease when two copies of the other version of the SNP are present. The data in this chart only apply to people with European ancestry.

(Note that for rs10795668, the less prevalent version actually protects against colorectal cancer – that’s why the change in odds is less than one. For rs4939827 the two versions are about equal in European populations.)

Type 2 Diabetes
Type 2 Diabetes occurs when chronically high blood sugar levels cause a breakdown of the body’s natural response to sugar. It can result in kidney failure, blindness, and circulatory problems that increase the risk of heart attack or stroke. In the United States, almost 21 million children and adults have diabetes, but the rate of new diagnoses is increasing.

Several SNPs have already been associated with Type 2 Diabetes (check out the Gene Journal (now called Health and Traits) article), but the established associations only explain a small proportion of the genetic component of the disease. Studies done to date may have been too small to find SNPs with very modest effects. SNPs with small effects, however, may be key to capturing the contribution that genes make to Type 2 Diabetes and many other common diseases.

Zeggini et al pooled the data from three large studies that previously examined SNPs and Type 2 Diabetes (more than 10,000 people total). The researchers then followed up on their findings in another 57,000 people (about 14,000 with Type 2 Diabetes).

The research replicated several SNPs that were found to be associated with Type 2 Diabetes in previous, smaller studies. But this new study also found six new associations. Two of these are available to 23andMe customers through the Genome Explorer (Browse Raw Data): rs7578597 and rs10923931, which is not included in the 23andMe Personal Genome Service but is equivalent to rs2793831, which is.

In the chart, each SNP’s rsid number is followed by the version of the SNP that is less prevalent in the population. The two columns labeled “effect” show the change in odds for developing Type 2 Diabetes when either one or two copies of the less prevalent version of the SNP are present compared with the odds of developing the disease when two copies of the other version of the SNP are present. So far these data apply only to people of European ancestry.

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