Cancer and IBD

The main cancer to consider in IBD is that of colorectal cancer. Both patients with colonic Crohn’s disease and ulcerative colitis are at increased risk of developing colorectal cancer. There is no increased risk of developing colorectal cancer in patients with isolated small bowel Crohn’s disease. The majority of patients with Crohn’s disease or ulcerative colitis will not develop colorectal cancer. Unfortunately, to date there is no blood test or stool test that can help predict who is at increased risk and should be more carefully screened among patients with IBD. Some factors do increase the risk, like increasing years of disease, having concurrent primary sclerosing cholangitis (a type of liver disease) or having a first degree relative with colorectal cancer.

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At present our best option for preventing colorectal cancer or for diagnosing it at an early stage when it is curable is by conducting regular surveillance colonoscopy. When this surveillance colonoscopy is undertaken biopsies are taken of any worrisome lumps identified but also randomly from flat areas in search of dysplasia (a change in the colon lining that suggests cancer is coming or already is present). Our approach is to conduct a surveillance colonoscopy starting at 8 years of disease, repeating it at 9 years and then conducting it every 3 years thereafter. Then at 20 years of disease we conduct colonoscopies annually. If after several annual colonoscopies there is little evidence even of chronic inflammatory changes we may spread out our colonoscopy intervals.

Relevant articles on colorectal cancer in IBD include:

Newly published studies in 2012

Nguyen G, Gulamhusein A, Bernstein CN. 5-Aminosalicylic acid is not protective against colorectal cancer in inflammatory bowel disease: A meta-analysis of non-referral populations. American Journal of Gastroenterology 2012; 107: 1298-1304.

In this study the researchers undertook a type of investigation called meta-analysis. This is a scientific to collate a number of different studies together to produce an average result of all the studies. The advantage of this approach is to increase the overall sample by merging a number of smaller studies into one analysis. These researchers separated out studies undertaken as large administrative database or population-based studies from those that were referral centre studies and conducted two separate meta analyses. In the large administrative database studies the result was pretty clear that 5-ASA drugs did not prevent against colorectal cancer development. In the analysis of referral centre studies the result clearly showed a benefit of 5-ASA drugs preventing colorectal cancer. So what should be believed? There are biases or flaws in both types of studies but the large administrative database studies are less prone to biases that can be manipulated by the researchers. We believe that the data available do not support the use of 5ASA as being preventative against developing colorectal cancer in patients with IBD.

Singh H, Bay D, Ip S, Bernstein CN, Nugent Z, Gheorghe R, Wightman R. Pathological reassessment of hyperplastic colonic polyps in a city-wide pathology practice: Implications for polyp surveillance recommendations. Gastrointestinal Endoscopy 2012; 2012:76: 1003-8.

This was a study of healthy adults who did not have IBD but were being colonoscoped to assess for colon polyps and colon cancer. In this study a large sample of a specific type of polyps, which are growths that may predispose to colon cancer, were re evaluated by two expert pathologists. The researchers found that some of the pathologists previously had reported some of these polyps as benign hyperplastic polyps and in fact on further review some had more ominous features- features of a serrated adenoma. The importance of this paper is to alert clinicians and pathologists to how these polyps may appear during endoscopy and how they may appear under the microscope when the pathologists are analyzing the biopsy tissue.

 

Studies from 2008-2011

Singh H, Demers A, Nugent Z, Bernstein CN. Screening for cervical and breast cancer among women with inflammatory bowel disease: A population-based study. Inflammatory Bowel Diseases 2010; 17: 1741-50.

There are limited data on the risk of nonmelanoma skin cancer among individuals with IBD, including those with or without exposure to immunosuppressant medications. Individuals with IBD (n = 9618) were identified from the University of Manitoba IBD. Epidemiology Database and matched with randomly selected controls (n = 91,378) based on age, sex, and postal area of residence on the date of index date of IBD diagnosis. Groups were followed up from the index date until a diagnosis of any invasive cancer (including non melanoma squamous cell cancer) death, migration from the province, or the end of the study (December 31, 2009), whichever came first. Cox regression analysis was performed to calculate the relative risk of non melanoma squamous cell cancer among the individuals with IBD, adjusting for frequency of ambulatory care visits and socioeconomic status. Of the individuals followed, 1696 were diagnosed with basal cell skin cancer and 341 were diagnosed with squamous cell skin cancer. Individuals with IBD had an increased risk for basal cell carcinoma, compared with controls (hazard ratio, 1.20; 95% confidence interval [CI], 1.03-1.40). Among patients with IBD, use of thiopurines increased the risk of squamous cell carcinoma (hazard ratio, 5.40; 95% CI, 2.00-14.56), compared with controls. Use of thiopurines also was associated with squamous cell carcinoma in a case-control, nested analysis of individuals with IBD (odds ratio, 20.52; 95% CI, 2.42-173.81). We concluded that the risk of basal cell carcinoma could be increased among individuals with IBD. Use of thiopurines (azathioprine and 6-mercaptopurine)  increases the risk of squamous cell carcinoma among individuals with IBD. SO IBD patients using these drugs should be alerted to sn avoidance or regular use of sun screen and/or routine check-ups with a dermatologist for any new skin lesion.

 

Singh H, Demers A, Nugent Z, Bernstein CN. Screening for cervical and breast cancer among women with inflammatory bowel disease: A population-based study. Inflammatory Bowel Diseases 2010; 17: 1741-50

There are limited data on rates and predictors of cervical and/or breast cancer screening among women with inflammatory bowel disease (IBD). Immunosuppressant medications used to manage IBD may increase the risk of cervical cancer precursor lesions. In this study the University of Manitoba IBD Epidemiology Database was linked to available databases in Manitoba that comprehensively record mammography screening and Papanicolaou (Pap) testing. Women diagnosed with IBD prior to 2002 were matched to up to 10 Manitoba residents without the disease. Pap testing and mammography for women ages 18 to 69 was assessed in the years 2002-2004. The utilization of Pap tests and mammograms in the two groups were compared. Among women with IBD, the differences in screening between those with and without exposure to immunosuppressant medications and/or corticosteroids were assessed and the effects of age, socioeconomic status, prior diagnostic testing, and intensity of healthcare utilization was assessed.

In all, 54% of the 2344 women with IBD and 52% of the 15,333 controls had regular Pap tests. On multivariate analyses, older age, lower socioeconomic status, lower intensity of healthcare utilization, Crohn’s disease (versus ulcerative colitis), and exposure to immunosuppressant medications were independent predictors of lower use of Pap testing.

The odds ratio of having Pap testing in women with IBD on mmunosuppressants and/or corticosteroids compared to women with IBD not on these drugs was 0.67 (95% confidence interval 0.46, 0.99). Forty-five percent of women with IBD had mammography. Although there were no significant differences in the use of mammograms in women with or without IBD or among women with IBD with or without exposure to immunosuppressant medications, only 47% of women with IBD in the target age group had mammograms regularly. We concluded that even though there is aneed for higher testing, women with IBD on immunosuppressant medications are less likely to undergo Pap testing. Healthcare providers involved in the care of women with IBD need to remind these individuals about regular preventive care.

Bernstein CN, Nugent Z, Blanchard JF. A population-based study of 5-aminosalicylate use and colorectal cancer in IBD. American Journal of Gastroenterology 2011; 106: 731-6

We aimed to determine if use of 5-aminosalicylates (5-ASA) was associated with a reduced risk of colorectal cancer  in people with IBD. We used the population-based University of Manitoba IBD Epidemiology Database that tracks all health-care visits from 1984 to 2008 of all Manitobans with IBD and all prescription medication use since 1995. In 2008, there were 8,744 subjects with IBD (ulcerative colitis 4,325, Crohn’s disease 4,419, females 4,851, males 3,893). In study I, we assessed the incidence of colorectal cancer among 5-ASA users (≥1 year, ≥5 years of cumulative use) compared with nonusers. In study II, we assessed a cohort of those with colorectal cancer (n=101) diagnosed in 1995-2008, matched to a control cohort by age, sex, disease duration, and disease diagnosis without colorectal cancer (n=303), and logistic analysis was undertaken. For study I, the hazard ratio for colorectal cancer among 5-ASA users was 1.04 (95% confidence interval (CI) 0.67-1.62, P=0.87) at ≥1 year of use and 2.01 (95% CI 1.04-3.9, P=0.038) at ≥ 5 years of use with no difference when assessing by diagnosis. Males, but not females, using 5-ASA for ≥ 5 years had an increased risk of colorectal cancer. In study II, colorectal cancer cases had similar use of any 5-ASA compared with controls for ≥ 1 year of use (1.02, 95% CI 0.60-1.74) or ≥ 5 years (1.96, 95% CI 0.84-4.55), and a similar mean number of 5-ASA prescriptions at 10 vs. 11 (P=0.8) and a similar mean number of dose days at 330 vs. 410 (P=0.69). Our results support the majority of studies to date that 5-ASA is not chemoprophylactic in IBD for colorectal cancer.

Published studies related to colorectal cancer in 2008-09

Singh H, Demers AA, Nugent Z, Mahmud S, Bernstein CN. Risk of cervical abnormalities in women with IBD: a population-based nested case-control study. Gastroenterology 2009; 136: 451-8.

Elsewhere it was reported that women with IBD might have an increased risk of abnormal PAP smears. Hence we evaluated the risk of cervical abnormalities in women with IBD by linking our University of Manitoba IBD Epidemiology Database with the provincial PAP smear database. We found there was no association between cervical abnormalities and ulcerative colitis. The increase in risk in women with Crohn’s disease was limited to those exposed to 10 or more prescriptions of oral contraceptives. The combined exposure to corticosteroids and immunosuppressants was associated with increased risk of cervical abnormalities. In conclusion, our findings did not support an association between IBD itself and the risk of developing cervical abnormalities. An increased risk in patients given a combination of corticosteroids and immunosuppressants should be considered in managing women with IBD. All women with IBD should ensure they have regular PAP smears, but particularly those women using steroids, azathioprine, 6-mercaptopurine, methotrexate, or anti-TNF agents.

Bezabeh T, Somorji R, Dolenko B, Bryskina N, Levin B, Bernstein CN, Jeyarajah E, Steinhart AH, Rubin D, Smith ICP. Detecting colorectal cancer by 1H magnetic resonance spectroscopy of fecal extracts. NMR in Biomedicine 2009; 22: 593-600.

We present a new methodology based on magnetic resonance spectroscopy of stool samples for the non-invasive detection of colorectal cancer. 523 subjects (412 with no colon cancers or polyps and 111 with colorectal cancer, who were scheduled for colonoscopy or surgery) were recruited to donate a single sample of stool. One-dimensional (1)H magnetic resonance spectroscopy (MRS) experiments were performed on the stool samples. We found that this technique could reliably distinguish stool from persons with normal colonoscopies from persons harboring a colorectal cancer. Therefore, this technique has the potential to be a useful addition to the current screening tools for persons at risk for colorectal cancer. Currently this technique is being developed in the healthy population without IBD.

Bernstein CN. Surveillance programmes for colorectal cancer in inflammatory bowel disease: have we got it right? Gut 2008; 57: 1194-6.

This report reviews approaches to colorectal cancer surveillance in chronic colitis. It is an editorial written in response to a Dutch paper that assessed the years of disease at which surveillance colonoscopy is initiated.

Singh H, Demers AA, Nugent Z, Mahmud S, Bernstein CN. Risk of cervical abnormalities in women with IBD: a population-based nested case-control study. Gastroenterology 2009; 136: 451-8.

Elsewhere it was reported that women with IBD might have an increased risk of abnormal PAP smears. Hence we evaluated the risk of cervical abnormalities in women with IBD by linking our University of Manitoba IBD Epidemiology Database with the provincial Cervical Cancer Screening Program Database, which records all PAP smears performed (and their follow-up tests) in the province for the women between the ages of 18 and 69 years.

We found there was no association between cervical abnormalities and ulcerative colitis. The increase in risk in women with Crohn’s disease was limited to those exposed to 10 or more prescriptions of oral contraceptives. The combined exposure to corticosteroids and immunosuppressants was associated with increased risk of cervical abnormalities.

In conclusion, our findings did not support an association between IBD itself and the risk of developing cervical abnormalities. An increased risk in patients given a combination of corticosteroids and immunosuppressants should be considered in managing women with IBD. All women with IBD should ensure they have regular PAP smears, but particularly those women using steroids, azathioprine, 6-mercaptopurine, methotrexate, or anti-TNF agents.