Colonic neoplasia and celiac disease: A systematic review

Table 1 Protective factors within the intestinal barrier

Factor	Type	Role in barrier protection	Notes	Ref.
KIF	Cytoskeletal protein	Maintains cytoskeletal structures. Keratin 7 and 20 upregulation leads to crypt widening, while keratin 8 downregulation is observed during inflammation	KIFs are influenced by stress and inflammation. Types 1 (acidic) and 2 (basic) are noted	Helenius et al[10]
Paneth cell granules	Cellular component	Synthesizes and releases antimicrobial peptides to maintain the microbial barrier	Low zinc concentration is associated with granule depletion	Kelly et al[11]
Microbiome environment	Microbial component	Influences the risk of certain diseases, including celiac disease; enteroviral infections are linked to increased disease risk	The intestinal microbiome’s composition and health have systemic effects	Clinton et al[12]
γδ T cells	Immune cells	Reside in the intestinal wall; overactivation and control by IL-15 are crucial for gut homeostasis	Elevated IL-15 expression disrupts gut hemostasis	Suzuki et al[13]
IEL	Immune cells	γ/δ CD3+ and CD8+ IELs are increased in the duodenum of celiac patients, indicating a protective or reactive role	The distribution of IELs varies between the duodenum and colon in celiac patients	[14]

KIF: Keratin intermediate filament; IEL: Intraepithelial lymphocytes; IL: Interleukin.

Table 2 Studies showing the association between celiac disease and colorectal adenoma

Ref.	Year	Country	Design	Celiac disease cases	Colon adenoma cases	Survival and mortality findings
Pereyra et al[22]	20131	Argentina	Multicenter, retrospective case–control study	118	Polyps: 24; adenoma: 18; advanced colonic lesions: 3	On multivariate analysis, there was increased risk of colonic adenoma observed in CD patient aged ≥ 75 years old. Polyps, OR = 6.59 (CI: 1.64-26.57), P = 0.008; adenoma, OR = 8.12 (CI: 1.83-35.94), P = 0.005; advanced colonic lesions, OR = 15.14 (CI: 1.23-186.67), P = 0.03
Lasa et al[107]	20181	Argentina	Hospital-based retrospective case control study	57	Adenoma: 27; left sided adenoma: 21; right sided adenoma: 10; advanced adenoma: 6	Adenoma, OR = 2.31 (CI: 1.18-4.53), P = 0.01; left sided adenoma, OR = 2.69 (CI: 1.29-5.61), P = 0.006; right sided adenoma, OR = 1.18 (CI: 0.5-2.76), P = 0.7; advanced adenoma, OR = 1.27 (CI: 0.43-3.71), P = 0.6
Lasa et al[109]	20182	Argentina	Systemic review and meta-analysis	367		No increased prevalence of colorectal adenomas in CD patients, compared with controls [OR = 0.94 (CI: 0.65-1.38), P = 0.76], and no significant difference was observed when assessing the prevalence of advanced adenomas [OR = 0.97 (CI: 0.48-1.97)], no significant heterogeneity was observed (I2 = 26%)
González et al[110]	20122	Argentina	Hospital-based retrospective case control study	178	Polyps: 9; adenoma: 7; advanced colonic lesions: 2	No significant association between CD and colorectal adenoma among CD patients and control; polyps: OR = 1.48 (CI: 0.59-3.73), adenoma: OR = 1.89 (CI: 0.66-5.42), advanced colonic lesions: OR = 1.34 (CI: 0.26-7.05)
Lebwohl et al[108]	20101	United States	Hospital-based retrospective case control study	180	23	On multivariate analysis, age (OR per year 1.04, 95%CI: 1.02-1.07) and male gender (OR = 2.33, 95%CI: 1.36-3.98) are associated with adenomas; no significant association between CD and adenoma detection (OR = 0.75, 95%CI: 0.41-1.34), P = 0.33

¹Studies showed increased risk.

²Studies showed decreased risk.

CD: Celiac disease; OR: Odds ratio; CI: Confidence interval.

Table 3 Studies investigating the risk of colorectal cancer in celiac disease patients

Ref.	Year	Country	Study design	Celiac disease cases	Cancer cases	Survival and mortality findings
Askling et al[111]	20021	Sweden	Population-based prospective cohort study	11019	26	Compared to the general population: Increased risk of colon cancer: SIR = 1.9 (95%CI: 1.2-2.8); similar risk of rectum cancer: SIR = 0.8 (95%CI: 0.3-1.6)
Elfström et al[112]	20121	Sweden	Nationwide retrospective cohort study (biopsy based)	Total CD patients: 28882	First year (colon: 49, rectum: 14); after the first year (colon: 88, rectum: 30)	For colon cancer, in the CD total group, the HR was 7.94 (5.21-12.12) at the first year of FU and 1.10 (0.87-1.39) after the first year of FU. For rectum cancer, in the CD total group, the HR was 2.57 (1.36-4.86) at the first year of FU and 0.58 (0.4-0.85) after the first year of FU. In the CD with active inflammation group for colon cancer, the HR was 9.02 (6.08-13.4) at the first year of FU and 1.01 (0.76-1.34) after the first year of FU; for rectum cancer, the HR was 3.49 (1.45-8.43) at the first year of FU and 0.83 (0.55-1.27) after the first year of FU. In the latent CD group for colon cancer, the HR was 4.03 (1.26-12.9) at the first year of FU and 0.39 (0.09-1.62) after the first year of FU; for rectum cancer, the HR was 13.6 (4.04-45.7) at the first year
				CD with inflammation (marsh I-II) 12860	At first year (colon: 60, rectum: 8); after the first year (colon: 57, rectum: 25)
				Latent CD 3705	First year (colon: 4, rectum: 6); after first year (colon: 2)
Ilus et al[113]	20141	Finland	Population-based prospective cohort study	32439	133 colon cancers, 51 rectal cancers	Increased risk of colon cancer: SIR = 1.35 (95%CI: 1.13-1.58); no increased risk of rectum cancer: SIR = 0.82 (95%CI: 0.61-1.07)
Onwuzo et al[6]	20231	United States	Retrospective multicenter	1890	82880	Increased risk of colon cancer, OR of CRC in CD 10.18 (95%CI: 9.72-10.65), P < 0.001). On multivariate regression analysis: OR of CRC in: Males 1.49 (95%CI: 1.36-1.63); African Americans 1.51 (95%CI: 1.35-1.68); type 2 diabetes mellitus 2.71 (95%CI: 2.66-2.76); smokers 2.49 (95%CI: 2.44-2.54); obese individuals 2.21 (95%CI: 2.17-2.25); alcoholics 1.72 (95%CI: 1.66-1.78)
Viljamaa et al[114]	20062	Finland	Population-based prospective cohort study	781	4	No increased risk of colon and rectum cancer: SIR = 1.1 (95%CI: 0.3-2.8)
Silano et al[115]	20072	Italy	Hospital-based prospective cohort study	1968	7	No increased risk of colon cancer: SIR = 1.1 (95%CI: 0.68-1.56), P < 0.001
Goldacre et al[83]	20082	United States	Hospital-based retrospective cohort study	1997	11 colon cancer, 4 rectum cancer	No increased risk (excluding cases occurred within the first year after CD diagnosis). Colon: Adjusted RR = 1.23 (95%CI: 0.61-2.20); rectum: Adjusted RR = 1.04 (95%CI: 0.28-2.67)
Lebwohl et al[116]	20222	Sweden	Population-based cohort study	47241	448	No increased risk of colorectal cancer: HR = 1.06 (95%CI: 0.96-1.18)
Landgren et al[117]	20112	United States	Hospital-based retrospective cohort study		11 colon cancer, 9 rectum cancer	No increased risk: Colon: Adjusted RR = 0.85 (95%CI: 0.47-1.54); rectum: Adjusted RR = 1.29 (95%CI: 0.67-2.48)
Grainge et al[19]	20122	United Kingdom	Population-based retrospective cohort study	435	6	No increased risk of colorectal cancer: SIR = 1.17 (95%CI: 0.43-2.54)
Volta et al[23]	20142	Italy	Multicenter retrospective cohort study	1757	6	Decreased risk of colon carcinoma compared to the general population: SIR = 0.29 (95%CI: 0.07-0.45)
van Gils et al[84]	20182	Netherlands	Population-based retrospective case control study	349	105	Increased risk during the first year after CD diagnosis [RR = 5.1 (95%CI: 3.1-8.3)], then decreased risk afterward period [RR = 0.7 (95%CI: 0.5-0.9, P < 0.001)]; sensitivity analyses showed decreased risk for colorectal carcinoma after CD diagnosis [RR = 0.7 (95%CI: 0.5-0.9), P = 0.02]
Haider et al[118]	20242	United States	Population-based study	529842	1752	No significant association, OR = 0.99 (0.93-1.06), P = 0.7087

¹Studies reported increased risk.

²Studies reported no or decreased risk.

SIR: Standardized incidence ratio; CI: Confidence interval; CD: Celiac disease; HR: Hazard ratio; FU: Follow-up; OR: Odds ratio; CRC: Colorectal carcinoma; RR: Rate ratio.