Association of cancer with comorbid inflammatory conditions and treatment in patients with Lynch syndrome

Table 1 Demographics, genetic diagnosis, surveillance, surgical history, and cancer in hereditary non-polyposis colorectal cancer

	Inflammatory disease present, n = 21	Controls, n = 43	P value
Current age (yr), mean ± SD	53.9 ± 15.7	53.8 ± 7.8	0.97
Gender, n (%)
Female	12 (57.1)	25 (58.1)	0.94
Race, n (%)
White	17 (81.0)	40 (93.0)	0.34
Black	1 (4.8)	1 (2.3)
Others	3 (14.3)	2 (4.6)
Smoking Status, n (%)
Former/current	9 (42.9)	20 (46.5)
Never Smoker	12 (57.1)	23 (53.5)	0.72
Family History of Cancer, n (%)
Colon	13 (61.9)	33 (78.6)	0.16
LS Cancer	11 (52.4)	24 (57.1)	0.72
Other cancers	12 (57.1)	25 (58.1)	0.94
LS MMRPV, n (%)	14 (66.7)	21 (67.4)	1
MLH1	5 (23.8)	10 (23.3)
MSH2	3 (14.3)	7 (16.3)
MSH6	2 (9.5)	4 (9.3)
PMS2	4 (19.0)	8 (18.6)
No MMRPV	7 (33.3)	14 (32.6)
Age of HNPCC diagnosis, mean ± SD
LS	43.6 ± 14.0	45.4 ± 7.6	0.66
No MMRPV	49.0 ± 5.4	46.3 ± 2.2	0.59
Screening colonoscopies
Median total number	5 (IQR 3.0-6.0)	4 (IQR 2.0-6.0)	0.19
Median years between colonoscopies	1.0 (IQR 1.0-1.5)	1.0 (IQR 1.0-1.6)	0.87
History of complete or partial colectomy	15 (76.2)	23 (53.5)	0.08
TAH-BSO (% of females in each group)	10 (83.3)	19 (76.0)	0.8
History of Prophylactic TAH-BSO (% of females in each group)	6 (50.0)	7 (28.0)	0.27
Proportion of patients with any cancer, n (%)	16 (84.2)	33 (76.7)	0.74
Cancer Incidence-10 yr follow up	12 (57.1)	20 (46.5)	0.42
Age at Diagnosis of first cancer (yr), mean ± SD	45.5 ± 14.6	43.8 ± 7.1	0.67

HNPCC: Hereditary non-polyposis colorectal cancer; LS: Lynch syndrome; MMRPV: Mismatch repair pathogenic variant; TAH- BSO: Total abdominal hysterectomy-bilateral salpingo-oophorectomy.

Table 2 Cancers observed based on presence or absence of a comorbid inflammatory condition over 10 yr of follow up, n (%)

Number of patients who developed a cancer	CID present, n = 21	No CID, n = 43
	12 (57.1)	20 (46.5)
Lynch syndrome specific cancers
Colorectal	9 (42.9)	12 (27.9)
Endometrial	2 (9.5)	8 (18.6)
Small Bowel	0 (0)	1 (2.3)
Urothelial	1 (4.8)	1 (2.3)
Non-Lynch Syndrome-specific cancers
Breast	1 (4.8)	0 (0)
Nasopharynx	1 (4.8)	0 (0)
Prostate	1 (4.8)	0 (0)
Ovarian	0 (0)	1 (2.3)
B-Cell Lymphoma	1 (4.8)	0 (0)

CID: Comorbid inflammatory condition.

Table 3 Distribution of cancers based on genetic diagnosis by comorbid inflammatory condition status

	CID present			CID non present
	CRC	LS specific1	All other	CRC	LS specific	All other
MLH1	2 (40.0)	2 (40.0)	1 (20.0)	2 (20.0)	2 (20.0)	0 (0)
MSH2	2 (66.7)	0 (0)	1 (33.3)	2 (28.6)	4 (57.1)	1 (14.3)
MSH6	0 (0)	0 (0)	0 (0)	2 (50.0)	1 (25.0)	0 (0)
PMS2	2 (50.0)	0 (0)	1 (25.0)	0 (0)	2 (25.0)	0 (0)
No MMRPV	3 (42.9)	1 (14.3)	1 (14.3)	6 (42.9)	1 (7.1)	0 (0)

¹LS Specific cancers other than colorectal cancer. These include endometrial, small bowel and urothelial.

CRC: Colorectal cancer; LS: Lynch syndrome; CID: Comorbid inflammatory condition.

Table 4 Characteristics of individuals with a comorbid inflammatory condition based on medication exposure

Characteristic	Exposed	Unexposed	P value
	n = 9 (39.5)	n = 12 (60.5)
Current age (yr), mean ± SD	54.2 ± 20	53.6 ± 12.4	0.7
Gender, n (%)
Female	4 (44.4)	8 (66.7)	0.4
Race, n (%)
Caucasian	7 (77.8)	10 (83.3)	1
Others	2 (22.2)	2(16.7)
Smoking Status, n (%)
Former/current	4 (44.4)	5 (41.7)	1
Never smoked	4 (55.6)	7 (58.3)
Previous history of cancer, n (%)	2 (22.2)	2 (16.7)	1
Family history of cancer, n (%)
LS specific cancer	6 (66.7)	5 (41.7)	0.39
All other cancers	6 (44.4)	8 (66.7)	0.4
Duration of Follow up, (yr), median (IQR)	10.0 (9.0-22.0)	8.5 (5.3-17.3)	0.38
Comorbid disease, n (%)	3 (33.3)	4 (33.3)	1
Crohn’s disease	2 (22.2)	3 (25.0)
Ulcerative colitis	1 (11.1)	1 (8.3)
Rheumatic disease, n (%)	6 (66.7)	8 (66.7)	1
Pathogenic variant
MLH1	2 (22.2)	3 (25.0)
MSH2	2 (22.2)	1 (8.3)
MSH6	0 (0)	2 (16.7)	0.68
PMS2	2 (22.2)	2 (16.7)
MSI-H	3 (33.3)	4 (33.3)
Cancer after CID diagnosis	7 (77.8)	5 (41.7)	0.18
Time to Cancer After Diagnosis of CID, (yr), median (IQR)	5.0 (2.0-16.0)	5.0 (1.0-10.5)	0.64
Age at Diagnosis of first cancer (yr), median (IQR)	49 (23.0-54.0)	48 (44.0-50.0)	0.99

HNPCC: Hereditary non-polyposis colorectal cancer; LS: Lynch syndrome; MMRPV: Mismatch repair pathogenic variant; CID: Comorbid inflammatory disease.

Table 5 Details of exposure for each patient with type of cancer and age at diagnosis of cancer

Disease	Genetic Diagnosis	Medication	Duration /mo	Dose/mg	Cancer type and stage	Age at diagnosis of cancer
Ulcerative colitis	PMS2	Ustekinumab,	12		Colon II	19
		Golimumab	6
		Vedolizumab	24
Crohn’s disease	MLH1	6MP	24	50	Colon I	57
Crohn’s disease	PMS2	Adalimumab	18		Colon III	17
		Golimumab	6
		Vedolizumab	12
Sarcoidosis	MLH1	MTX	60	15	Renal I	49
Rheumatoid arthritis	LLS	Etanercept	120		Breast I, Colon IV	76
		Tofacitinib	9
		MTX	35	15
		Azathioprine	72	50
Rheumatoid arthritis	MSH2	MTX	4	20	Colon II	51
		Rituximab	72
Psoriatic arthritis	MSI-H	Adalimumab	36		Colon III	44
		Ustekinumab	10
		MTX	36	15
Dermatomyositis	MSH2	MTX	12	15	NA	NA
Rheumatoid arthritis	MSI-H	MTX	120	10	NA	NA

MSI-H: High microsatellite instability; MTX: Methotrexate; 6MP: 6-mercaptopurine, NA: Not applicable (no cancer seen during duration of the study).