1. Inflammatory Bowel Disease Confers a Lower Risk of Colorectal Cancer to Females Than to Males SVERRE SÖDERLUND, FREDRIK GRANATH, OLLE BROSTRÖM, PER KARLÉN, ROBERT LÖFBERG, ANDERS EKBOM, and JOHAN ASKLING. GASTROENTEROLOGY 2010;138:1697–1703 Journal club 2010.05.17 R2. 홍성훈

2. Background Differences in cancer risk between male and female animal after chronic inflammation. For CRC, a male to female gap is 1.5:1. (from 50 years) Estrogen →nuclear factor-κB activity and IL-6 production (infl. by carcinogen) → protection against cancer among female animals. In a mouse model of colitis-associated CRC, males deficient of nuclear factor- κB(MyD-88) had an increased resistance to cancer development. In this study, we hypothesized that women with IBD would be at lower risk for CRC compared with men with IBD.

3. Matreial and Methods Setting - A population-based cohort study - Including 3 large Swedish cohorts of patients with UC or CD. - With follow-up evaluation for cancer occurrence through national registers. - The diagnosis of CRC was obtained through the Swedish National Cancer Register since 1960. Study Population - The Uppsala cohort of IBD - The Stockholm cohort of IBD - The Stockholm pan-colitis register - Follow up by linking these 3 cohorts to · the Swedish Causes of Death Register 1960–2004 · the Swedish National Cancer Register 1960–2004 · the Swedish Hospital Discharge Register 1964–2004

4. Matreial and Methods

5. Statistics. - The occurrence of CRC in males and females was compared within the IBD cohort, and btw the IBD cohort & gen. population. - Within the IBD cohort · the cumulative incidence of CRC using Kaplan–Meier curves. · the relative risk of CRC for male by using Cox regression. - The relative risk of CRC vs the general population using standardized incidence ratios (SIRs) separately for males and females. - Sex-specific Kaplan–Meier curves depicting the development of the observed and the expected cumulative incidences of CRC.

6. Results Overall Occurrence of CRC - 7607 pts. with IBD were followed up for a total of 171,000 person-years. - 196 cases of CRC in 188 patients were registered (overall incidence of 110 cases per 100,000 person years) - Men : 118 cases (135/100,000 person-years) - Women : 70 cases (83/100,000 person-years)

7. Results No differences in cancer stage distribution

8. Results (Male-Female contrasts within the cohort) 60% higher rate RR = 1.6

9. Results (Btw the cohort & the gen. population) MEN 180% higher rate SIR = 2.6 WOMEN 90% higher rate SIR = 1.9

10. Results (Subset analysis restricted to pan-colitis) MEN 180% higher rate SIR = 2.6 WOMEN 90% higher rate SIR = 1.9

11. Conclusion IBD confers a lower risk of CRC to females than to males. Estrogens may act to protect against IBD- associated CRC.