Cancer Risk in Inflammatory Bowel Disease: A 6-Year Prospective Multicenter Nested Case–Control IG-IBD Study

Abstract

Background In a 6-year, multicenter, prospective nested case–control study, we aimed to evaluate risk factors for incident cancer in inflammatory bowel disease (IBD), when considering clinical characteristics of IBD and immunomodulator use. The secondary end point was to provide characterization of incident cancer types. Methods All incident cases of cancer occurring in IBD patients from December 2011–2017 were prospectively recorded in 16 Italian Group for the Study of Inflammatory Bowel Disease units. Each of the IBD patients with a new diagnosis of cancer was matched with 2 IBD patients without cancer, according to IBD phenotype (ulcerative colitis [UC] vs Crohn’s disease [CD]), age (±5 years), sex. Risk factors were assessed by multivariate logistic regression analysis. Results Cancer occurred in 403 IBD patients: 204 CD (CD cases), 199 UC (UC cases). The study population included 1209 patients (403 IBD cases, 806 IBD controls). Cancer (n = 403) more frequently involved the digestive system (DS; 32%), followed by skin (14.9%), urinary tract (9.7%), lung (6.9%), genital tract (6.5%), breast (5.5%), thyroid (1.9%), lymphoma (2.7%, only in CD), adenocarcinoma of the small bowel (SBA; 3.9%, 15 CD, 1 pouch in UC), other cancers (15.9%). Among cancers of the DS, colorectal cancer (CRC) more frequently occurred in UC (29% vs 17%; P < 0.005), whereas SBA more frequently occurred in CD (13% vs 6.3% P = 0.039). In CD, perforating (B3) vs non-stricturing non-perforating (B1) behavior represented the only risk factor for any cancer (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.33–4.11). In CD, risk factors for extracolonic cancer (ECC) were a B3 vs B1 and a stricturing (B2) vs B1 behavior (OR, 2.95; 95% CI, 1.62–5.43; OR, 1.79; 95% CI, 1.09–2.98). In UC, risk factors for ECC and for overall cancer were abdominal surgery for UC (OR, 4.63; 95% CI, 2.62–8.42; OR, 3.34; 95% CI, 1.88–5.92) and extensive vs distal UC (OR, 1.73; 95% CI, 1.10–2.75; OR, 1.99; 95% CI, 1.16–3.47). Another risk factor for ECC was left-sided vs distal UC (OR, 1.68; 95% CI, 1.00–2.86). Inflammatory bowel disease duration was a risk factor for skin and urinary tract cancers. Conclusions Perforating CD, extensive UC, and abdominal surgery for UC were identified as risk factors for overall incident cancer and for ECC. The clinical characteristics associated with severe IBD may increase cancer risk.

The Link between Oral and Gut Microbiota in Inflammatory Bowel Disease and a Synopsis of Potential Salivary Biomarkers

“…One population-based cohort study showed that IBD patients had a lower survival rate from colorectal cancer compared to non-IBD patients [21]. In another recent, 6-year prospective, multicenter, nested, case-control study published in 2019, perforating CD, extensive UC, and abdominal surgery for UC were major risk factors identified for the incidence of cancer overall as well as in extracolonic cancer [22]. With the greater risk of cancers and mortality, research on effective IBD treatment and accurate diagnoses using non-invasive methods have been increasing alongside growing cases worldwide.…”

Somatic mutational profiles and germline polygenic risk scores in human cancer

“…Inflammatory bowel disease PRS were found to be associated with somatic mutational profiles in multiple hormone-related cancers (breast, endometrial, and prostate cancer). Previous studies have established CD and UC as risk factors for overall cancer 54,55,56,57,58 , but whether these associations are driven by shared genetic susceptibility or other common lifestyle and environmental factors remains unanswered by these epidemiological studies. In the present work, we found robust positive associations between IBD PRS (IBD, UC, and CD) and somatic mutations in breast cancer.…”

The Regulation of Intestinal Inflammation and Cancer Development by Type 2 Immune Responses

“…Lack of physical activity, smoking, and poor diet were associated with a moderately increased risk, while the highest CRC risk was found in patients with a family history of CRC or patients with IBD [95]. Supporting this view, a recent publication identified extensive UC and perforating CD as significant risk factors for any malignancy [96]. Colitis-associated cancer (CAC) accounts for 1-2% of all CRCs.…”