P2024 - Human Immunogenetics of Gastrointestinal Malignancies: A Systematic Review of Cases With Primary Immune Deficiencies

Monday, October 25, 2021

10:30 AM – 4:15 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Award: Presidential Poster Award

Presenting Author(s)

Beishi Zheng, MD

Woodhull Medical and Health Care Center
BROOKLYN, NY, United States

Award: Presidential Poster Award

Beishi Zheng, MD¹, Bing Chen, MD², Howard Chung, MD³, Siming Sun, BS⁴, Lyam Ciccone, MD⁵, Kitson Deane, MD⁶, Peter Green, MD⁷, Benjamin Lebwohl, MD⁷, Anil Rustgi, MD⁸, Timothy Wang, MD⁸, Xiaofei Kong, MD, PhD⁸
¹Woodhull Medical and Health Care Center, Brooklyn, NY; ²Mount Sinai Morningside and West Hospitals, New York, NY; ³Queens Hospital Center, Forest Hills, NY; ⁴Columbia University Irving Medical Center, New York, NY; ⁵New York University Woodhull Medical Center, New York, NY; ⁶Woodhull Medical Center, Brooklyn, NY; ⁷Columbia University Medical Center, New York, NY; ⁸New York-Presbyterian/Columbia University Medical Center, New York, NY

Introduction: The immune system plays a pivotal role in cancer surveillance and the tumor microenvironment. People with primary immune deficiency diseases (PIDD) are prone to chronic and recurrent mucosal infections and inflammation, together with their potential intrinsic epithelium dysfunction due to monogenic defects, which might lead to an early-onset gastrointestinal malignancy requiring special attention for gastroenterologists and clinical immunologists.

Methods: We systematically reviewed all the reported cases with the clinical diagnosis both of primary immune deficiency and gastrointestinal malignancies using three databases (Pubmed, Scopus, EMBASE). With 68 manuscripts reviewed, we found a total of 149 PIDD cases meeting our inclusion criteria.

Results: With a total of 149 PIDD cases, 95 presented with gastric cancer, 13 with small bowel malignancy, 35 with colorectal cancer, 3 with esophagus malignancy and 3 patients without clear tumor position recorded. Gastric adenocarcinoma, small bowel lymphoma, and colon adenocarcinoma were the most common cancer types. The most common PIDD associated with gastrointestinal malignancy was common variable immune deficiency (CVID), comprising 59.1% of the patients. The age of gastrointestinal cancer diagnosis ranged from 3 to 82 years, with the median age of 40 years. Compared to populational epidemiological data, Individuals with PIDD appear to have an early onset of GI malignancy, 20 years to 35 years younger than the general population. We also observed a significant survival disadvantage when PIDD cases developed colorectal malignancies. However, the molecular genetic diagnostic rate is only about 12%, with the following genes are most frequently reported, including ATM, RLTPR(CARMIL-2), CTLA-4.

Discussion: Patients with primary immune deficiency who develop malignancy do so at an earlier age than that of the general population. Surveillance programs to identify malignancies at an early stage and genetic studies are required to delineate the immunogenetic contribution and identify screening tools to early-onset gastrointestinal malignancy.

Figure: a. Flow diagram for study selection b. Distribution of tumor position c. Distribution of PIDD types d. Kaplan- Meier survival analysis of colorectal malignancy for PIDD patients and normal population. e. Percentile of patients with gastric malignancy at different ages f. Percentile of patients with colorectal malignancy at different ages

	Total cases (n=149)	Stomach (n=95)	Expected Stomach* (n=95)	P value	Odd ratio	Colorectal (n=35)	Expected colorectal* (n=35)	P value	Odd ratio
Gender
Male	84(56.4%)	53(55.8%)	62(65.1%)	0.1816	0.6717	21(60%)	20(56.5%)	0.8083	1.125
Female	58(38.9%)	41(43.2%)	33(34.9%)	0.234	1.426	10(28.6%)	15(43.5%)	0.2123	0.5333
NA	7(4.7%)	1(1.1%)	NA	NA	NA	4(11.4%)	NA	NA	NA
Age group
0-24	36(24.2%%)	14(14.7%)	0(0.1%)	0.0001	Infinity	16(45.7%)	0(0.3%)	< 0.0001	Infinity
25-44	46(30.9%)	31(32.6%)	3(2.9%)	< 0.0001	14.85	9(25.7%)	1(2.7%)	0.0063	11.77
45-64	42(28.2%)	29(30.5%)	17(17.7%)	0.0421	2.016	7(20.0%)	6(17.0%)	0.7586	1.208
≥65	24(16.1%)	20(21.1%)	75(79.1%)	< 0.0001	0.07111	3(8.6%)	28(80%)	< 0.0001	0.02344
NA	1(0.7%)	1(1.1%)	NA	NA	NA	0(0%)	NA	NA	NA

Table: Table1. Clinical characteristics of GI malignancy in PIDD
* based on SEER data

Disclosures:

Beishi Zheng indicated no relevant financial relationships.

Bing Chen indicated no relevant financial relationships.

Howard Chung indicated no relevant financial relationships.

Siming Sun indicated no relevant financial relationships.

Lyam Ciccone indicated no relevant financial relationships.

Kitson Deane indicated no relevant financial relationships.

Peter Green indicated no relevant financial relationships.

Benjamin Lebwohl: Anokion – Consultant. Takeda – Consultant.

Anil Rustgi indicated no relevant financial relationships.

Timothy Wang indicated no relevant financial relationships.

Xiaofei Kong indicated no relevant financial relationships.

Beishi Zheng, MD¹, Bing Chen, MD², Howard Chung, MD³, Siming Sun, BS⁴, Lyam Ciccone, MD⁵, Kitson Deane, MD⁶, Peter Green, MD⁷, Benjamin Lebwohl, MD⁷, Anil Rustgi, MD⁸, Timothy Wang, MD⁸, Xiaofei Kong, MD, PhD⁸. P2024 - Human Immunogenetics of Gastrointestinal Malignancies: A Systematic Review of Cases With Primary Immune Deficiencies, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.