Colitis-associated DNA aneuploidy and dysplasia in Crohn's disease and risk of colorectal cancer.

BACKGROUND: There is uncertainty about how patients with Crohn's colitis should be monitored for colorectal cancer (CRC). By analogy to ulcerative colitis, regular colonoscopy with biopsies for dysplasia has been used. We describe the occurrence of dysplasia and DNA aneuploidy in a cohort of patients with Crohn's colitis. METHODS: In all, 245 patients with extensive colitis (225 with a firm diagnosis of Crohn's disease, and 20 diagnosed as indeterminate colitis) at Stockholm Söder Hospital and Karolinska University Hospital, Huddinge were included. They were followed with regular colonoscopies with biopsies both for dysplasia and DNA aneuploidy. The cumulative occurrence of DNA aneuploidy and dysplasia was estimated using Kaplan-Meier curves. Time sequences and interactions between DNA aneuploidy, dysplasia, and CRC were studied using Cox regression analysis, adjusted for age, sex, and age at diagnosis. RESULTS: During a median follow-up time of 9.2 person-years, DNA aneuploidy was found in 53 patients (22%), with 10 patients having multifocal aneuploidy and high S-phase values. Dysplasia was found in 42 patients (17%), 10 having multifocal dysplasia. Relative risk (RR) of dysplasia given DNA aneuploidy was 5.3 (95% confidence interval [CI] 2.3-12). RR of CRC given dysplasia was 10 (95% CI 2-50), and RR of CRC given aneuploidy was 1.5 (95% CI 0.3-9.3). CONCLUSIONS: Dysplasia and DNA aneuploidy including S-phase analysis may complement stratification of patients with Crohn's

Inflammatory bowel disease confers a lower risk of colorectal cancer to females than to males.

BACKGROUND & AIMS: Reported differences in cancer risk between male and female animals after chronic inflammation suggest that estrogen has inflammation-modifying properties. Little is known about these effects in human beings. Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC); we studied differences in inflammation-associated CRC between men and women patients with IBD. METHODS: By using a large population-based cohort (n = 7607) of individuals diagnosed with IBD from 1954 to 1989, we assessed the sex-specific incidence of CRC from 1960 to 2004. Incidence was determined within the cohort (modeled using Poisson regression) and compared with the general population (assessed as standardized incidence ratios) using data from national Swedish health and census registers. RESULTS: During 171,000 person-years of follow-up evaluation, 196 new cases of CRC were observed (123 in males, 73 in females). Males with IBD had a 60% higher risk of CRC (relative risk [RR], 1.6; 95% confidence interval [CI], 1.2-2.2) than females (cumulative incidence 40 years after IBD diagnosis, 8.3% vs 3.5%). Compared with the rate of CRC among the general population, in males with IBD the RR was 2.6 and the 95% CI was 2.2-3.1, whereas in females the RR was 1.9 and the 95% CI was 1.5-2.4. The effect of sex was limited to the period after 10 years of follow-up evaluation (RR, 0.8 before vs 2.2 after), and to patients diagnosed before age 45 (RR, 2.1 before vs 1.0 after). CONCLUSIONS: IBD confers a lower risk of CRC to females than to males.

Decreasing time-trends of colorectal cancer in a large cohort of patients with inflammatory bowel disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a risk factor for colorectal cancer (CRC). There have been marked changes in the management and treatment of IBD over the past decades, but little is known about how these changes have impacted morbidity and mortality (time trends in risk) of CRC in patients with IBD. METHODS: We assessed cancer occurrence and mortality in a large population-based cohort of patients with IBD who were diagnosed from 1954 to 1989 (n = 7607). Through register links, we collected data on vital status of all registered cases of CRC, as well as intestinal surgeries and mortalities from CRC through 2004. Relative risks for CRC incidence and mortality, by calendar period of follow-up evaluation, were assessed within the cohort (using Poisson regression and taking age, sex, extent of IBD, and time since IBD diagnosis into account) and also compared with the general population using standardized incidence and mortality ratios. RESULTS: During 198,227 person-years of follow-up evaluation for the 7607 patients with IBD, 188 new cases of CRC were observed (crude incidence, 95 per 100,000; 95% confidence interval, 82-109); 92 deaths from CRC were registered. Within the IBD cohort, as well as vs the general population, the incidence of CRC showed a tendency towards a decline whereas the mortality from CRC decreased several-fold from the 1960s through 2004. CONCLUSIONS: Over the past 35 years, the risk of diagnosis of CRC in patients with IBD has not declined significantly, but the risk of dying of CRC has decreased substantially.