Abstract
Gastrointestinal tract acid-446 (GTA-446) is a long-chain polyunsaturated fatty acid present in the serum. A reduction of GTA-446 levels in colorectal cancer (CRC) patients has been reported previously. Our study compared GTA-446 levels in subjects diagnosed with CRC at the time of colonoscopy to the general population. Serum samples and pathology data were collected from 4,923 representative subjects undergoing colonoscopy and from 964 subjects from the general population. Serum GTA-446 levels were determined using a triple-quadrupole tandem mass spectrometry method. A low-serum GTA-446 level was based on the bottom tenth percentile of subjects with low risk based on age (40–49 years old) in the general population. Eighty-six percent of newly diagnosed CRC subjects (87% for stages 0–II and 85% for stages III–IV) showed low-serum GTA-446 levels. A significant increase in the CRC incidence rate with age was observed in subjects with low GTA-446 levels (p = 0.019), but not in subjects with normal levels (p = 0.86). The relative risk of CRC given a low GTA-446 level was the highest for subjects under age 50 (10.1, 95% confidence interval [C.I.] = 6.4–16.4 in the reference population, and 7.7, 95% C.I. = 4.4–14.1 in the colonoscopy population, both p < 0.0001), and declined with age thereafter. The CRC incidence rate in subjects undergoing colonoscopy with low GTA-446 levels was over six times higher than for subjects with normal GTA-446 levels and twice that of subjects with gastrointestinal symptoms. The results show that a low-serum GTA-446 level is a significant risk factor for CRC, and a sensitive predictor of early-stage disease.
Highlights
Colorectal cancer (CRC) is the second leading cause of cancer death in Canada and it is estimated that 22,200 new diagnoses and 8,900 deaths will occur in 2012.1 Financial and societal costs of late-stage diagnosis are significantly greater compared to early-stage diagnosis, owing to increased costs of treatment and poor survival rate.[2,3] Current screening guidelines are based primarily on fecal occult blood testing and colonoscopy, but these screening approaches continue to struggle with compliance issues,[4,5] have questionable costbenefit[6] and show variable diagnostic performance depending on the method.[7]
The current hypothesis is that a reduction of serum Gastrointestinal tract acid-446 (GTA-446) levels over time represents a compromised ability to protect against accumulating chronic inflammation and abnormal cell growth, which leads to a pro-cancer environment.[9,10]
What’s new? This study showed that 86% of CRC patients had low GTA-446 levels
Summary
Colorectal cancer (CRC) is the second leading cause of cancer death in Canada and it is estimated that 22,200 new diagnoses and 8,900 deaths will occur in 2012.1 Financial and societal costs of late-stage diagnosis are significantly greater compared to early-stage diagnosis, owing to increased costs of treatment and poor survival rate.[2,3] Current screening guidelines are based primarily on fecal occult blood testing and colonoscopy, but these screening approaches continue to struggle with compliance issues,[4,5] have questionable costbenefit[6] and show variable diagnostic performance depending on the method.[7]. GTA-446 is inversely correlated with age and CRC incidence rate, and exhibits both anti-proliferative and antiinflammatory activities.[9,10] The current hypothesis is that a reduction of serum GTA-446 levels over time represents a compromised ability to protect against accumulating chronic inflammation and abnormal cell growth, which leads to a pro-cancer environment.[9,10]. The purpose of our prospective study was to determine the percentage of CRC patients with low GTA-446 levels. This study showed that 86% of CRC patients had low GTA-446 levels. The relative risk of CRC was higher in subjects with low than in those with normal GTA-446 levels. The lack of increased CRC incidence with age among patients with normal GTA-446 levels suggested that low GTA-446 levels could be driving the age increase in CRC incidence rates. GTA-446 testing should be considered as a novel CRC risk-stratification tool
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