Bacteria, Blood & Genes: 3 New Ways To Diagnose Colon Cancer

In its early stages, colon cancer doesn’t always cause symptoms, making proactive diagnosis difficult. While some patients will experience rectal bleeding, or changes in their bowel habits, most people are diagnosed on the basis of a routine colonoscopy – prior to the appearance of any symptoms. To make matters more difficult, colon cancer’s early warning signs often resemble benign conditions, the American Cancer Society reports. Hemorrhoids, irritable bowel syndrome and gastrointestinal infections can all look very similar in the beginning.

Bacteria May Hold Key To Earlier Colon Cancer Diagnosis

Proposed research out of Pennsylvania could promise a sea-change in the diagnosis of colorectal cancers. In collaboration with scientists at Johns Hopkins University and non-profit healthcare center Reading Health System, doctors at Digestive Disease Associates are set to investigate the link between gastrointestinal bacteria and colon cancer.

Today, all the team has is a theory: GI bacteria could spur the development of tumors in the digestive tract. Two years ago, Johns Hopkins researchers discovered biofilms, densely-woven “mats” of interdependent bacteria, attached to the vast majority of colon cancers and polyps.

Lead author Cynthia L. Sears MD says that these biofilms can disrupt the natural layer of mucus that normally protects epithelial cells within the bowels. Biofilms are most prevalent in right-sided tumors, Sears explains, “in fact, [the bacterial groupings are] virtually a universal feature of tumors that appear in that section of the colon.”

Even more evidence came in 2015, when a Johns Hopkins-led study in mice found that biofilms appear to be locked in a “vicious circle” with colon cancer cells. On a molecular level, changes in cells consistent with the development of cancer seemed to promote further biofilm growth, which in turn promoted a boost in cancer development. But this cycle hasn’t been observed in human patients – yet. Over the next five years, the researchers will put their theory to the test, gathering 2,000 patients in Baltimore and Reading, Pennsylvania.

Balancing External & Internal Environments

Beyond assisting in the accurate diagnosis of cancer, the research could also widen our understanding of what causes colon tumors in the first place. While some cancers can be attributed to genetic factors, the majority are likely caused by environmental factors, researchers say.

Frank Giardiello, a professor at Johns Hopkins, thinks we may soon be able to add digestive bacteria to the list of environmental and behavioral risks, which already includes obesity, saturated fats and a sedentary lifestyle. “We’re now suggesting one of the major causes of colon cancer is bacteria,” Giardiello told the Reading Eagle, “having these biofilms attached to the colon cancer.”

The study is being funded by the National Cancer Institute. The federal agency tasked with researching new cancer treatments and diagnostic techniques has asked Congress for a 7% increase in funding over last year’s $5.21 billion budget.

New Blood Test Comes With Significant Cautions

While colonoscopies are still the standard in colon cancer diagnosis, a new blood-based test just received FDA approval in April.

The test is simple; it can be bundled with a patient’s other routine blood tests, but inexact, reports Harvard Health Publications. Blood tests won’t be replacing colonoscopies anytime soon, says Harvard Medical School’s Andrew Chan MD. The best way to judge a screening technique’s effectiveness, Chan describes, is based on how well it improves clinical outcomes. A good test will catch colon cancer early enough for a doctor to treat it successfully. The new blood test hasn’t been proved effective in that way, Chan explains.

That doesn’t mean we should throw out the blood test, which is called Epi proColon, entirely. Around 35% of people aren’t being screened for colon cancer in any way. The test’s convenience could easily filter through some of these patients, Chan says, although he worries that its ease could “lull patients into a false sense of security.” The test looks for a DNA biomarker that has been tied to colon cancer, but can’t check for precancerous polyps or other signs of a tumor.

Lynch Syndrome Awareness Gains Ground

Awareness surrounding genetic factors is growing, too. Foremost among these hereditary, or inheritable, risks is Lynch syndrome, a condition found in around 1 out of every 440 Americans.

To date, researchers have narrowed down the genes involved in Lynch syndrome to one family of genetic instructions, so-called “mismatch repair” genes, or MMR for short. Normally, mismatch repair genes do exactly what it sounds like they do, cleaning up mistakes and erroneous duplications in the genetic duplication process. But in people with Lynch syndrome, mutations in the MMR genes undermine the effort to fix errors in genetic copying. That means more mutations, more often, and an increased risk of developing cancer.

While Lynch syndrome is most often cited in relation to colorectal cancers, the condition also increases the risk for uterine, ovarian, pancreatic and urinary tract cancer.

Can We Diagnose Lynch Syndrome?

Lynch syndrome runs in families, and researchers were first tipped off to the genetic condition’s existence by a strange cluster of clinical features, which seemed to be more prevalent in some relatives:

  • early age of cancer onset
  • higher risk of more than one primary tumor
  • right-sided colorectal tumors

One feature of Lynch syndrome, though, is positive. Even after a cancer diagnosis, people with Lynch syndrome have a better clinical outcome than others, the National Cancer Institute says.

Genetics Help, But Clinical Screening Still Necessary

By 1990, researchers had determined that these familial characteristics were a major tip-off in diagnosing colon cancer effectively. But they didn’t jump straight to genetic testing immediately. Instead, government agencies advised patients to seek out early colonoscopies if their families fit the “Amsterdam criteria”:

  • three or more cases of colorectal cancer over two or more generations
  • at least one family member diagnosed before the age of 50
  • no evidence of familial adenomatous polyposis, another genetic condition that greatly increases the risk of colon cancer

Once Lynch syndrome was boiled down to faulty MMR genes, around 1993, genetic analysts began investigating non-symptomatic patients for suspicious alterations in germline cells. These tests were largely unsuccessful, since “no more than half of suspected [Lynch syndrome] cases have detectable pathologic mutations,” according to the National Cancer Institute. Other strategies soon emerged, though, and today, doctors rely on a mix of clinical, familial and genetic evidence to identify people with Lynch syndrome.

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