J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 15, Number 6, June 2023, pages 310-320

Colon Cancer Risk Following Intestinal Clostridioides difficile Infection: A Longitudinal Cohort Study

Figure 2. A life-test model summary of the relationship between the incidence rate of colon cancer in the Clostridioides difficile cohort as compared to the non-C. difficile cohort.

**Table 1.** Demographic Characteristics of the Adults Examined^a
Parameter examined	Non-Cdiff cohort (n = 292,136)	Cdiff cohort (n = 964)
^aAll adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. All adults diagnosed with Cdiff and/or colon cancer within the first year of enrollment were excluded. ^bAll adults were specified to have a county of residence at the time of initial enrollment and at the end of the enrollment period. There are a total of 67 counties in the state of Florida, which are grouped by the state of Florida based upon geographical areas into 11 districts. ^cPersonal history of tobacco abuse (ICD-9 code: 305.1x). ^dPersonal history of alcohol abuse/dependence (ICD-9 code: 303.xx or 305.0x). ^ePersonal history of drug abuse/dependence (ICD-9 code: 304.xx, 305.2x, 305.3x, 305.34, 305.5x, 305.6x, 305.7x, 305.8x or 305.9x). ^fPersonal history of overweight/obesity (ICD9 code: 278.00, 278.01, or 278.02). ^gFamily history of any type of cancer (ICD-9 code: V16.xx). Cdiff: Clostridioides (formerly known as Clostridium) difficile; CI: confidence interval; SD: standard deviation.

Gender (%)
Male	83,473 (28.57%)	337 (34.96%)
Female	208,663 (71.43%)	627 (64.97%)
Date of birth in years, mean ± SD (range)	1942 ± 18.27 (1,898 - 1,984)	1947 ± 14.47 (1,901 - 1,982)
Age in years at initial study enrollment, mean ± SD (range)	51.24 ± 17.96 (20 - 96)	50.11 ± 14.18 (20 - 91)
Residency at initial enrollment (%)^b
District 1	13,356 (4.57%)	39 (4.05%)
District 2	18,296 (6.26%)	60 (6.22%)
District 3	27,652 (9.47%)	111 (11.52%)
District 4	23,551 (8.06%)	105 (10.89%)
District 5	17,663 (6.05%)	89 (9.23%)
District 6	31,024 (10.62%)	82 (8.51%)
District 7	23,647 (8.09%)	91 (9.44%)
District 8	11,817 (4.04%)	51 (5.29%)
District 9	15,682 (5.37%)	49 (5.08%)
District 10	14,522 (4.97%)	52 (5.39%)
District 11	94,926 (32.50%)	235 (24.38%)
Residency at the end enrollment (%)^b
District 1	13,352 (4.57%)	41 (4.25%)
District 2	18,359 (6.28%)	58 (6.02%)
District 3	28,369 (9.71%)	118 (12.24%)
District 4	23,740 (8.13%)	103 (10.69%)
District 5	17,919 (6.13%)	91 (9.44%)
District 6	30,980 (10.60%)	86 (8.92%)
District 7	23,843 (8.16%)	89 (9.23%)
District 8	12,030 (4.12%)	51 (5.29%)
District 9	15,714 (5.38%)	46 (4.77%)
District 10	14,853 (5.08%)	47 (4.88%)
District 11	92,977 (31.83%)	234 (24.27%)
Personal history
Tobacco abuse (%)^c	1,938 (0.66%)	11 (1.14%)
Alcohol abuse/dependence (%)^d	17,475 (5.98%)	153 (15.87%)
Drug abuse/dependence (%)^e	17,088 (5.85%)	159 (16.49%)
Overweight/obesity (%)^f	15,287 (5.23%)	162 (16.80%)
Family history
Cancer (%)^g	2,684 (0.92%)	24 (2.49%)
Person-years
Total	2,036,767	2,575
Mean ± SD (range)	6.97 ± 0.37 (0.008 - 7.00)	2.67 ± 1.98 (0.003 - 7.00)

Table 1. Demographic Characteristics of the Adults Examined^a

Parameter examined

Non-Cdiff cohort (n = 292,136)

Cdiff cohort (n = 964)

^aAll adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. All adults diagnosed with Cdiff and/or colon cancer within the first year of enrollment were excluded. ^bAll adults were specified to have a county of residence at the time of initial enrollment and at the end of the enrollment period. There are a total of 67 counties in the state of Florida, which are grouped by the state of Florida based upon geographical areas into 11 districts. ^cPersonal history of tobacco abuse (ICD-9 code: 305.1x). ^dPersonal history of alcohol abuse/dependence (ICD-9 code: 303.xx or 305.0x). ^ePersonal history of drug abuse/dependence (ICD-9 code: 304.xx, 305.2x, 305.3x, 305.34, 305.5x, 305.6x, 305.7x, 305.8x or 305.9x). ^fPersonal history of overweight/obesity (ICD9 code: 278.00, 278.01, or 278.02). ^gFamily history of any type of cancer (ICD-9 code: V16.xx). Cdiff: Clostridioides (formerly known as Clostridium) difficile; CI: confidence interval; SD: standard deviation.

Gender (%)

Male

83,473 (28.57%)

337 (34.96%)

Female

208,663 (71.43%)

627 (64.97%)

Date of birth in years, mean ± SD (range)

1942 ± 18.27 (1,898 - 1,984)

1947 ± 14.47 (1,901 - 1,982)

Age in years at initial study enrollment, mean ± SD (range)

51.24 ± 17.96 (20 - 96)

50.11 ± 14.18 (20 - 91)

Residency at initial enrollment (%)^b

District 1

13,356 (4.57%)

39 (4.05%)

District 2

18,296 (6.26%)

60 (6.22%)

District 3

27,652 (9.47%)

111 (11.52%)

District 4

23,551 (8.06%)

105 (10.89%)

District 5

17,663 (6.05%)

89 (9.23%)

District 6

31,024 (10.62%)

82 (8.51%)

District 7

23,647 (8.09%)

91 (9.44%)

District 8

11,817 (4.04%)

51 (5.29%)

District 9

15,682 (5.37%)

49 (5.08%)

District 10

14,522 (4.97%)

52 (5.39%)

District 11

94,926 (32.50%)

235 (24.38%)

Residency at the end enrollment (%)^b

District 1

13,352 (4.57%)

41 (4.25%)

District 2

18,359 (6.28%)

58 (6.02%)

District 3

28,369 (9.71%)

118 (12.24%)

District 4

23,740 (8.13%)

103 (10.69%)

District 5

17,919 (6.13%)

91 (9.44%)

District 6

30,980 (10.60%)

86 (8.92%)

District 7

23,843 (8.16%)

89 (9.23%)

District 8

12,030 (4.12%)

51 (5.29%)

District 9

15,714 (5.38%)

46 (4.77%)

District 10

14,853 (5.08%)

47 (4.88%)

District 11

92,977 (31.83%)

234 (24.27%)

Personal history

Tobacco abuse (%)^c

1,938 (0.66%)

11 (1.14%)

Alcohol abuse/dependence (%)^d

17,475 (5.98%)

153 (15.87%)

Drug abuse/dependence (%)^e

17,088 (5.85%)

159 (16.49%)

Overweight/obesity (%)^f

15,287 (5.23%)

162 (16.80%)

Family history

Cancer (%)^g

2,684 (0.92%)

24 (2.49%)

Person-years

Total

2,036,767

2,575

Mean ± SD (range)

6.97 ± 0.37 (0.008 - 7.00)

2.67 ± 1.98 (0.003 - 7.00)

**Table 2.** Demographic Characteristics of the Adults Diagnosed With Colon Cancer^a Examined^b
Cohort examined (n)	Gender (%)	Date of birth, mean ± SD (range)	Age of initial diagnosis, mean ± SD (range)	Incidence rate per 1,000 person-years (n)
^aAdults diagnosed with colon cancer were diagnosed according to the International Code for Disease 9th revision with the code 153.xx. ^bAll adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. All adults diagnosed with Cdiff and/or colon cancer within the first year of enrollment were excluded. Cdiff: Clostridioides (formerly known as Clostridium) difficile; SD: standard deviation.
All adults (n = 293,100)	Male: 753 (31.79%)	1933 ± 15.3 (1,899 - 1,980)	61.76 ± 13.77 (21 - 92)	1.16 (2,369)
	Female: 1,616 (68.21%)
Non-Cdiff cohort (n = 292,136)	Male: 751 (31.81%)	1933 ± 15.1 (1,899 - 1,979)	61.78 ± 13.77 (21 - 92)	1.16 (2,361)
	Female: 1,610 (68.19%)
Cidff cohort (n = 964)	Male: 2 (25.00%)	1943 ± 10.5 (1,924 - 1,955)	61.9 ± 12.9 (47 - 85)	3.11 (8)
	Female: 6 (75.00%)

Table 2. Demographic Characteristics of the Adults Diagnosed With Colon Cancer^a Examined^b

Cohort examined (n)

Gender (%)

Date of birth, mean ± SD (range)

Age of initial diagnosis, mean ± SD (range)

Incidence rate per 1,000 person-years (n)

^aAdults diagnosed with colon cancer were diagnosed according to the International Code for Disease 9th revision with the code 153.xx. ^bAll adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. All adults diagnosed with Cdiff and/or colon cancer within the first year of enrollment were excluded. Cdiff: Clostridioides (formerly known as Clostridium) difficile; SD: standard deviation.

All adults (n = 293,100)

Male: 753 (31.79%)

1933 ± 15.3 (1,899 - 1,980)

61.76 ± 13.77 (21 - 92)

1.16 (2,369)

Female: 1,616 (68.21%)

Non-Cdiff cohort (n = 292,136)

Male: 751 (31.81%)

1933 ± 15.1 (1,899 - 1,979)

61.78 ± 13.77 (21 - 92)

1.16 (2,361)

Female: 1,610 (68.19%)

Cidff cohort (n = 964)

Male: 2 (25.00%)

1943 ± 10.5 (1,924 - 1,955)

61.9 ± 12.9 (47 - 85)

3.11 (8)

Female: 6 (75.00%)

**Table 3.** Frequency Modeling Results to Evaluate the Incidence Rate of Colon Cancer^a in the Cdiff Cohort as Compared to the Non-Cdiff Cohort^b
Parameter examined	Cdiff cohort (n = 964)	Non-Cdiff cohort (n = 292,136)	Risk ratio (95% CI)
P < 0.05. ^aAdults diagnosed with colon cancer were diagnosed according to the International Code for Disease 9th revision with the code 153.xx. ^bAll adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. All adults diagnosed with Cdiff and/or colon cancer within the first year of enrollment were excluded. Cdiff: Clostridioides* (formerly known as Clostridium) difficile; CI: confidence interval.
Colon cancer (n)	8	2,361
Incidence rate per 1,000 person-years	3.11	1.16	2.68 (1.16 to 5.29)*
			1.95 (0.63 to 3.26)

Table 3. Frequency Modeling Results to Evaluate the Incidence Rate of Colon Cancer^a in the Cdiff Cohort as Compared to the Non-Cdiff Cohort^b

Parameter examined

Cdiff cohort (n = 964)

Non-Cdiff cohort (n = 292,136)

Risk ratio (95% CI)

Attributable rate per 1,000 person-years (95% CI)

*P < 0.05. ^aAdults diagnosed with colon cancer were diagnosed according to the International Code for Disease 9th revision with the code 153.xx. ^bAll adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. All adults diagnosed with Cdiff and/or colon cancer within the first year of enrollment were excluded. Cdiff: Clostridioides (formerly known as Clostridium) difficile; CI: confidence interval.

Colon cancer (n)

2,361

Incidence rate per 1,000 person-years

3.11

1.16

2.68 (1.16 to 5.29)*

1.95 (0.63 to 3.26)

**Table 4.** Cox Proportional Hazards Model Results Examining Colon Cancer^a Diagnoses in the Cdiff Cohort as Compared to Non-Cdiff Cohort^b
Model type	Variable	Hazards ratio (95% CI)
P < 0.01. P < 0.001. ^aAdults diagnosed with colon cancer. ^bAll adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. All adults diagnosed with Cdiff and/or colon cancer within the first year of enrollment were excluded. Cdiff: Clostridioides* (formerly known as Clostridium) difficile; CI: confidence interval.
Unadjusted model
	Cdiff (diagnosed vs. not diagnosed)	2.646 (1.321 to 5.301)*
Adjusted model I
	Cdiff (diagnosed vs. not diagnosed)	2.657 (1.325 to 5.330)*
	Gender (female vs. male)	0.840 (0.770 to 0.917)**
	Date of birth in years	1.034 (1.024 to 1.043)**
	Residency at initial enrollment	1.000 (0.995 to 1.006)
	Residency at end of enrollment	0.997 (0.991 to 1.003)
	Age in years at initial enrollment	1.072 (1.062 to 1.082)**

Table 4. Cox Proportional Hazards Model Results Examining Colon Cancer^a Diagnoses in the Cdiff Cohort as Compared to Non-Cdiff Cohort^b

Model type

Variable

Hazards ratio (95% CI)

*P < 0.01. **P < 0.001. ^aAdults diagnosed with colon cancer. ^bAll adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. All adults diagnosed with Cdiff and/or colon cancer within the first year of enrollment were excluded. Cdiff: Clostridioides (formerly known as Clostridium) difficile; CI: confidence interval.

Unadjusted model

Cdiff (diagnosed vs. not diagnosed)

2.646 (1.321 to 5.301)*

Adjusted model I

Cdiff (diagnosed vs. not diagnosed)

2.657 (1.325 to 5.330)*

Gender (female vs. male)

0.840 (0.770 to 0.917)**

Date of birth in years

1.034 (1.024 to 1.043)**

Residency at initial enrollment

1.000 (0.995 to 1.006)

Residency at end of enrollment

0.997 (0.991 to 1.003)

Age in years at initial enrollment

1.072 (1.062 to 1.082)**

**Table 5.** Cox Proportional Hazards Model Results Examining Colon Cancer^a Diagnoses in the Cdiff Cohort as Compared to Non-Cdiff Cohort^b When Excluding Adults Diagnosed With Cdiff and/or Colon Cancer Within the First Year of Enrollment
Model type	Variable	Hazards ratio (95% CI)
P < 0.05. P < 0.01. *P < 0.001. ^aAdults diagnosed with colon cancer. ^bAll adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. ^cAdults were assessed to determine whether at least one colonoscopy screening procedure was undertaken within the appropriate study period. ^dAdults were assessed to determine the total number of colonoscopy screening procedures undertaken within the appropriate study period. ^eAdults diagnosed with ulcerative colitis, infectious colitis, immunodeficiency, or any type of cancer before a Cdiff diagnosis were excluded. Adults diagnosed with ulcerative colitis, infectious colitis, immunodeficiency, or any types of cancer before a colon cancer diagnosis were excluded. Cdiff: Clostridioides* (formerly known as Clostridium) difficile; CI: confidence interval.
Adjusted model II
	Cdiff (diagnosed vs. not diagnosed)	2.673 (1.333 to 5.360)**
	Gender (female vs. male)	0.836 (0.767 to 0.913)***
	Date of birth in years	1.031 (1.022 to 1.041)***
	Residency at initial enrollment	1.000 (0.995 to 1.006)
	Residency at end of enrollment	0.997 (0.991 to 1.003)
	Age in Years at Initial Enrollment	1.069 (1.059 to 1.080)***
	≥ 1 colonoscopy screening procedure^c (yes vs. no)	1.210 (1.059 to 1.381)**
Adjusted model III
	Cdiff (diagnosed vs. not diagnosed)	2.667 (1.3330 to 5.348)**
	Gender (female vs. male)	0.836 (0.767 to 0.913)***
	Date of birth in years	1.031 (1.022 to 1.041)***
	Residency at initial enrollment	1.000 (0.995 to 1.006)
	Residency at end of enrollment	0.997 (0.991 to 1.003)
	Age in years at initial enrollment	1.069 (1.059 to 1.080)***
	Total colonoscopy screening procedures^d	1.161 (1.048 to 1.285)**
Adjusted model IV
	Cdiff (diagnosed vs. not diagnosed)	2.471 (1.232 to 4.958)*
	Gender (female vs. male)	0.821 (0.752 to 0.897)***
	Date of birth in years	1.024 (1.015 to 1.034)***
	Residency at initial enrollment	1.000 (0.994 to 1.006)
	Residency at end of enrollment	0.997 (0.991 to 1.003)
	Age in years at initial enrollment	1.064 (1.054 to 1.075)***
	Total colonoscopy screening procedures^d	1.105 (0.996 to 1.226)
	Family history of any type of cancer	3.547 (3.589 to 5.534)***
	Personal history of tobacco abuse	0.996 (0.516 to 1.923)
	Personal history of alcohol abuse/dependence	1.195 (0.975 to 1.466)
	Personal history of drug abuse/dependence	1.121 (0.892 to 1.409)
	Personal history of overweight/obesity	1.251 (1.043 to 1.500)3*
Adjusted model V^e
	Cdiff (diagnosed vs. not diagnosed)	2.970 (1.478 to 5.970)**
	Gender (female vs. male)	0.758 (0.681 to 0.844)***
	Date of birth in years	1.027 (1.015 to 1.039)***
	Residency at initial enrollment	1.000 (0.993 to 1.007)
	Residency at end of enrollment	0.997 (0.990 to 1.004)
	Age in years at initial enrollment	1.071 (1.058 to 1.084)***
	Total colonoscopy screening procedures^d	1.082 (0.946 to 1.237)
	Family history of any type of cancer	5.242 (3.975 to 6.913)***
	Personal history of tobacco abuse	1.075 (0.480 to 2.405)
	Personal history of alcohol abuse/dependence	1.217 (0.944 to 1.570)
	Personal history of drug abuse/dependence	1.153 (0.866 to 1.535)
	Personal history of overweight/obesity	1.242 (0.990 to 1.560)

Table 5. Cox Proportional Hazards Model Results Examining Colon Cancer^a Diagnoses in the Cdiff Cohort as Compared to Non-Cdiff Cohort^b When Excluding Adults Diagnosed With Cdiff and/or Colon Cancer Within the First Year of Enrollment

Model type

Variable

Hazards ratio (95% CI)

*P < 0.05. **P < 0.01. ***P < 0.001. ^aAdults diagnosed with colon cancer. ^bAll adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. ^cAdults were assessed to determine whether at least one colonoscopy screening procedure was undertaken within the appropriate study period. ^dAdults were assessed to determine the total number of colonoscopy screening procedures undertaken within the appropriate study period. ^eAdults diagnosed with ulcerative colitis, infectious colitis, immunodeficiency, or any type of cancer before a Cdiff diagnosis were excluded. Adults diagnosed with ulcerative colitis, infectious colitis, immunodeficiency, or any types of cancer before a colon cancer diagnosis were excluded. Cdiff: Clostridioides (formerly known as Clostridium) difficile; CI: confidence interval.

Adjusted model II

Cdiff (diagnosed vs. not diagnosed)

2.673 (1.333 to 5.360)**

Gender (female vs. male)

0.836 (0.767 to 0.913)***

Date of birth in years

1.031 (1.022 to 1.041)***

Residency at initial enrollment

1.000 (0.995 to 1.006)

Residency at end of enrollment

0.997 (0.991 to 1.003)

Age in Years at Initial Enrollment

1.069 (1.059 to 1.080)***

≥ 1 colonoscopy screening procedure^c (yes vs. no)

1.210 (1.059 to 1.381)**

Adjusted model III

Cdiff (diagnosed vs. not diagnosed)

2.667 (1.3330 to 5.348)**

Gender (female vs. male)

0.836 (0.767 to 0.913)***

Date of birth in years

1.031 (1.022 to 1.041)***

Residency at initial enrollment

1.000 (0.995 to 1.006)

Residency at end of enrollment

0.997 (0.991 to 1.003)

Age in years at initial enrollment

1.069 (1.059 to 1.080)***

Total colonoscopy screening procedures^d

1.161 (1.048 to 1.285)**

Adjusted model IV

Cdiff (diagnosed vs. not diagnosed)

2.471 (1.232 to 4.958)*

Gender (female vs. male)

0.821 (0.752 to 0.897)***

Date of birth in years

1.024 (1.015 to 1.034)***

Residency at initial enrollment

1.000 (0.994 to 1.006)

Residency at end of enrollment

0.997 (0.991 to 1.003)

Age in years at initial enrollment

1.064 (1.054 to 1.075)***

Total colonoscopy screening procedures^d

1.105 (0.996 to 1.226)

Family history of any type of cancer

3.547 (3.589 to 5.534)***

Personal history of tobacco abuse

0.996 (0.516 to 1.923)

Personal history of alcohol abuse/dependence

1.195 (0.975 to 1.466)

Personal history of drug abuse/dependence

1.121 (0.892 to 1.409)

Personal history of overweight/obesity

1.251 (1.043 to 1.500)3*

Adjusted model V^e

Cdiff (diagnosed vs. not diagnosed)

2.970 (1.478 to 5.970)**

Gender (female vs. male)

0.758 (0.681 to 0.844)***

Date of birth in years

1.027 (1.015 to 1.039)***

Residency at initial enrollment

1.000 (0.993 to 1.007)

Residency at end of enrollment

0.997 (0.990 to 1.004)

Age in years at initial enrollment

1.071 (1.058 to 1.084)***

Total colonoscopy screening procedures^d

1.082 (0.946 to 1.237)

Family history of any type of cancer

5.242 (3.975 to 6.913)***

Personal history of tobacco abuse

1.075 (0.480 to 2.405)

Personal history of alcohol abuse/dependence

1.217 (0.944 to 1.570)

Personal history of drug abuse/dependence

1.153 (0.866 to 1.535)

Personal history of overweight/obesity

1.242 (0.990 to 1.560)

**Table 6.** Cox Proportional Hazards Model Results Examining Colon Cancer^a Diagnoses in the Cdiff Cohort as Compared to Non-Cdiff Cohort^b When Excluding Adults Diagnosed With Cdiff and/or Colon Cancer Diagnoses Within the First 4 Years of Enrollment
Model type	Variable	Hazards ratio (95% CI)
P < 0.05. P < 0.01. *P < 0.001. ^aAdults diagnosed with colon cancer. ^b All adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. ^cAdults were assessed to determine whether at least one colonoscopy screening procedure was undertaken within the appropriate study period. ^dAdults were assessed to determine the total number of colonoscopy screening procedures undertaken within the appropriate study period. ^eAdults diagnosed with ulcerative colitis, infectious colitis, immunodeficiency, or any type of cancer before a Cdiff diagnosis were excluded. Adults diagnosed with ulcerative colitis, infectious colitis, immunodeficiency, or any types of cancer before a colon cancer diagnosis were excluded. Cdiff: Clostridioides* (formerly known as Clostridium) difficile; CI: confidence interval.
Adjusted model II
	Cdiff (diagnosed vs. not diagnosed)	4.064 (1.686 to 9.800)**
	Gender (female vs. male)	0.790 (0.705 to 0.885)***
	Date of birth in years	1.023 (1.011 to 1.035)***
	Residency at initial enrollment	1.001 (0.994 to 1.009)
	Residency at end of enrollment	0.995 (0.988 to 1.003)
	Age in years at initial enrollment	1.062 (1.048 to 1.076)***
	≥ 1 colonoscopy screening procedure^c (yes vs. no)	1.468 (1.189 to 1.811)***
Adjusted model III
	Cdiff (diagnosed vs. not diagnosed)	4.039 (1.675 to 9.739)**
	Gender (female vs. male)	0.790 (0.705 to 0.885)***
	Date of birth in years	1.023 (1.010 to 1.035)***
	Residency at initial enrollment	1.001 (0.994 to 1.009)
	Residency at end of enrollment	0.995 (0.988 to 1.003)
	Age in years at initial enrollment	1.062 (1.048 to 1.075)***
	Total colonoscopy screening procedures^d	1.353 (1.140 to 1.605)***
Adjusted model IV
	Cdiff (diagnosed vs. not diagnosed)	3.761 (1.559 to 9.078)**
	Gender (female vs. male)	0.786 (0.700 to 0.881)***
	Date of birth in years	1.016 (1.004 to 1.029)*
	Residency at initial enrollment	1.001 (0.994 to 1.009)
	Residency at end of enrollment	0.995 (0.988 to 1.003)
	Age in years at initial enrollment	1.057 (1.043 to 1.071)***
	Total colonoscopy screening procedures^d	1.302 (1.095 to 1.547)**
	Family history of any type of cancer	3.387 (2.427 to 4.725)***
	Personal history of tobacco abuse	0.929 (0.384 to 2.243)
	Personal history of alcohol abuse/dependence	1.369 (1.060 to 1.770)*
	Personal history of drug abuse/dependence	1.082 (0.799 to 1.465)
	Personal history of overweight/obesity	1.329 (1.047 to 1.686)*
Adjusted model V^e
	Cdiff (diagnosed vs. not diagnosed)	4.562 (1.885 to 11.041)***
	Gender (female vs. male)	0.735 (0.638 to 0.848)***
	Date of birth in years	1.019 (1.004 to 1.035)*
	Residency at initial enrollment	0.999 (0.990 to 1.008)
	Residency at end of enrollment	0.997 (0.988 to 1.007)
	Age in years at initial enrollment	1.064 (1.047 to 1.081)***
	Total colonoscopy screening procedures^d	1.320 (1.061 to 1.644)*
	Family history of any type of cancer	4.402 (2.954 to 6.559)***
	Personal history of tobacco abuse	1.231 (0.458 to 3.306)
	Personal history of alcohol abuse/dependence	1.377 (0.995 to 1.905)
	Personal history of drug abuse/dependence	1.086 (0.739 to 1.596)
	Personal history of overweight/obesity	1.357 (1.010 to 1.825)*

Table 6. Cox Proportional Hazards Model Results Examining Colon Cancer^a Diagnoses in the Cdiff Cohort as Compared to Non-Cdiff Cohort^b When Excluding Adults Diagnosed With Cdiff and/or Colon Cancer Diagnoses Within the First 4 Years of Enrollment

Model type

Variable

Hazards ratio (95% CI)

*P < 0.05. **P < 0.01. ***P < 0.001. ^aAdults diagnosed with colon cancer. ^b All adults were enrolled for 96 consecutive months. All adults had ≥ 8 outpatient office visits during their enrollment period. ^cAdults were assessed to determine whether at least one colonoscopy screening procedure was undertaken within the appropriate study period. ^dAdults were assessed to determine the total number of colonoscopy screening procedures undertaken within the appropriate study period. ^eAdults diagnosed with ulcerative colitis, infectious colitis, immunodeficiency, or any type of cancer before a Cdiff diagnosis were excluded. Adults diagnosed with ulcerative colitis, infectious colitis, immunodeficiency, or any types of cancer before a colon cancer diagnosis were excluded. Cdiff: Clostridioides (formerly known as Clostridium) difficile; CI: confidence interval.

Adjusted model II

Cdiff (diagnosed vs. not diagnosed)

4.064 (1.686 to 9.800)**

Gender (female vs. male)

0.790 (0.705 to 0.885)***

Date of birth in years

1.023 (1.011 to 1.035)***

Residency at initial enrollment

1.001 (0.994 to 1.009)

Residency at end of enrollment

0.995 (0.988 to 1.003)

Age in years at initial enrollment

1.062 (1.048 to 1.076)***

≥ 1 colonoscopy screening procedure^c (yes vs. no)

1.468 (1.189 to 1.811)***

Adjusted model III

Cdiff (diagnosed vs. not diagnosed)

4.039 (1.675 to 9.739)**

Gender (female vs. male)

0.790 (0.705 to 0.885)***

Date of birth in years

1.023 (1.010 to 1.035)***

Residency at initial enrollment

1.001 (0.994 to 1.009)

Residency at end of enrollment

0.995 (0.988 to 1.003)

Age in years at initial enrollment

1.062 (1.048 to 1.075)***

Total colonoscopy screening procedures^d

1.353 (1.140 to 1.605)***

Adjusted model IV

Cdiff (diagnosed vs. not diagnosed)

3.761 (1.559 to 9.078)**

Gender (female vs. male)

0.786 (0.700 to 0.881)***

Date of birth in years

1.016 (1.004 to 1.029)*

Residency at initial enrollment

1.001 (0.994 to 1.009)

Residency at end of enrollment

0.995 (0.988 to 1.003)

Age in years at initial enrollment

1.057 (1.043 to 1.071)***

Total colonoscopy screening procedures^d

1.302 (1.095 to 1.547)**

Family history of any type of cancer

3.387 (2.427 to 4.725)***

Personal history of tobacco abuse

0.929 (0.384 to 2.243)

Personal history of alcohol abuse/dependence

1.369 (1.060 to 1.770)*

Personal history of drug abuse/dependence

1.082 (0.799 to 1.465)

Personal history of overweight/obesity

1.329 (1.047 to 1.686)*

Adjusted model V^e

Cdiff (diagnosed vs. not diagnosed)

4.562 (1.885 to 11.041)***

Gender (female vs. male)

0.735 (0.638 to 0.848)***

Date of birth in years

1.019 (1.004 to 1.035)*

Residency at initial enrollment

0.999 (0.990 to 1.008)

Residency at end of enrollment

0.997 (0.988 to 1.007)

Age in years at initial enrollment

1.064 (1.047 to 1.081)***

Total colonoscopy screening procedures^d

1.320 (1.061 to 1.644)*

Family history of any type of cancer

4.402 (2.954 to 6.559)***

Personal history of tobacco abuse

1.231 (0.458 to 3.306)

Personal history of alcohol abuse/dependence

1.377 (0.995 to 1.905)

Personal history of drug abuse/dependence

1.086 (0.739 to 1.596)

Personal history of overweight/obesity

1.357 (1.010 to 1.825)*