Saturday, May 31, 2014

Crohn's Disease as a potential risk factor for Gastrointestinal Cancer development

At the age of ten, I was diagnosed with a Gastrointestinal condition known as Crohn's Disease. While this introduced several complications such as immune system compromise, severe abdominal pain, and difficulty with weight gain, I have since brought my condition under control, I am for all intents and purposes healthy and stable! Having a condition, however, pushes you to the brink of curiosity. Though I have learned a lot about Crohn's since being diagnosed, I have always wondered if a correlation exists between development of this disease and cancer risk. To my surprise, I stumbled upon a study conducted in Denmark looking specifically at patients with Crohn's disease and the resulting risk of cancer development.




Before introducing the study itself, a brief introduction to Crohn's Disease is required. Crohn's falls under a category of conditions referred to as Inflammatory Bowl Diseases, characterized by significant inflammation and ulceration of the Gastrointestinal tract. These symptoms are caused by the autoimmune nature of Crohn's, the immune system essential targets and attacks healthy cells within the GI tract. In relation to this study, the biological implications of Crohn's relationship with Cancer are unclear; the mechanism of this disease may or may not contribute to uncontrolled cell proliferation and DNA damage.

 The objective of this particular study was to determine the incidence of cancer among a cohort of Crohn's patients in Denmark and compare the observed numbers to the cancer incidence rates in the general Denmark population. 2,645 patients, with equal proportions of men and women, were identified from the Danish National Registry of Patients as having only Crohn's Disease with no additional, potentially confounding, IBD conditions. The study follow-ups began exactly 1 year following each patient's first hospitalization record for Crohn's Disease; this continued until patient's date of death, emigration, or 17 years after the start of the study.

Interestingly enough what they discover as a result were three unexpected data pairs, denoted by the highlighted regions in Table 2. In comparing the three separate Observed values (Obs) with that of the Expected values (Exp), what can we infer? For the purposes of analyzing the data, the "SIR" value is the standardized incidence ratio, calculated by dividing the observed number of cancers by the expected value; the higher the value the greater the occurrence of cancer.


A total of 143 cancers was observed within the participant pool of 2,645 Crohn's patients, a value slightly greater than what was expected. Additionally, the greatest majority of these cancers developed within the Gastrointestinal tract, proposing that the region affected by Crohn's Disease was also most vulnerable to observed cancer development. But most notably, the incidence of cancer within the small intestine yielded the greatest difference between Observed and Expected values. Crohn's Disease is most commonly localized within the small intestine, however can be found additionally in the colon and large intestines. (My particular case involves disease within the small intestines and colon.) Although the study did not receive information regarding the specific location of each patient's Crohn's, it is fair to assume that a good majority of participants had disease primarily affecting the small intestines. According to the study, "cancers of the small intestine occur very rarely in the general population," thus it seems appropriate to surmise that having Crohn's Disease is correlated with developing cancer within the small intestine.

So let us quickly scan the 5 cases of small intestine cancer observed for any similarities or parallel indications. As denoted in Table 3 below, three cases of Adenocarcinoma and two cases of a Malignant carcinoid resulted. The important value provided is the time between Crohn's and cancer development, similarities in duration offer evidence of a possible correlation. What we observe however is no concrete parallel, in addition to differing histologies, the time between disease development is scattered. While the values observed for cancer within the small intestines in Table 2 indicate a potential correlation between Crohn's presence and cancer development, the values below demonstrate a seemingly random and independent development of cancer.


Now, though the study itself is both fascinating and personally relevant, two issues present itself. Firstly, in regards to Crohn's, the development of disease, date of diagnosis, and first hospitalization record often fall within three different time points. Given that this study followed patients after first date of hospitalization, it is very likely that Crohn's disease had been prevalent in the body many years before. Thus, the method of study follow-up is not accurately measuring the time between Crohn's and cancer development, a variable integral to establishing the correlation between Crohn's and cancer.

Secondly, though the initial participant pool is large and reliable, the resulting cancer development values present a small and inconsistent data set. While the proportion of Crohn's patients that developed cancer within the small intestines is notable in comparison to the expected proportion, this equates to a mere 5 patients out of 2,645 that demonstrated significant values.

Even still, as a Crohn's patient, this research is important; I will certainly not dismiss the findings of this study. While there was no evidence of association between Crohn's Disease and development of any extraintestinal cancer, patients within this study demonstrated an increased number of overall cancer development, gastrointestinal cancer, and cancer within the small intestines. Such findings warrant further research and propose that Crohn's Disease may in fact serve as a potential risk factor for Gastrointestinal cancer development.

Sources

Mellemkj√¶r, Lene, et al. "Crohn's Disease and Cancer Risk (Denmark)." Cancer Causes and Control 

11.2 (2000): 145-50. Print.