Aspirin, cyclooxygenase inhibition and colorectal cancer

Table 1 Summary of the associations between regular use of aspirin and risk of colorectal cancer in case-control and cohort studies

Study type	n	Aspirin	Controls	OR (95%CI)	P value
Case-control
Any ASA	26	10464/25618	28300/47834	0.67 (0.60-0.74)	< 0.0001
Maximum reported ASA	17	1551/12659	2664/18153	0.62 (0.58-0.67)	< 0.0001
ASA ≥ 5 yr	10	971/7682	1534/10029	0.68 (0.63-0.75)	< 0.0001
Daily ASA	4	165/1254	349/1523	0.49 (0.40-0.60)	< 0.0001
Daily ASA ≥ 5 yr	1	66/1668	121/1973	0.63 (0.46-0.86)	0.004
Standard cohort
Any Aspirin	11	3791/2764414	3623/2514652	0.85 (0.82-0.89)	< 0.0001
Maximum reported ASA	8	661/664475	1858/1374905	0.78 (0.71-0.84)	< 0.0001
ASA ≥ 5 yr	4	889/1 022192	1311/1304760	0.76 (0.70–0.82)	< 0.0001
Daily ASA	5	741/658536	1115/819288	0.80 (0.73-0.88)	< 0.0001
Daily ASA ≥ 5 yr	1	60/38302	420/232116	0.68 (0.52-0.90)	0.0060
Nested case-control
Any ASA	6	2215/8926	65 099/109526	0.87 (0.75-1.00)	0.0700
Maximum reported ASA	5	206/4457	8302/40948	0.67 (0.58-0.77)	< 0.0001
ASA ≥ 5 yr	1	116/228	23704/37935	0.62 (0.48-0.81)	< 0.0001
Daily ASA	1	53/165	8744/22975	0.77 (0.55-1.07)	0.1400
Daily ASA ≥ 5 yr	1	29/141	7274/21505	0.51 (0.34-0.76)	0.0120

Modified from Algra et al[8]. Estimates from standard cohort studies are based on results adjusted for age and other baseline clinical characteristics. ASA: Aspirin.

Table 2 Characteristics of trials included in Rothwell et al study and details of post-trial follow-up

	Thromobosis prevention trial	Swedish aspirin low dose trial	UK-TIA aspirin trial	British doctors aspirin trial
ASA comparison	75 mg/d vs placebo	75 mg/d vs placebo	300 mg vs 1200 mg/d vs placebo	500 mg/d vs placebo
Recruitment period	1989-1992	1984-1989	1979-1985	1978-7199
Median duration of scheduled treatment in original trial (yr)	6.9	2.7	4.4	6
Year post-trial follow up extended to	2009	2007	2006	2002

Modified from Algra et al[8]. ASA: Aspirin.

Table 3 Clinical effects of aspirin on sporadic colorectal cancer (clinical trials)

	Rothwell et al meta analysis	Physician’s health study	Women’s health study
ASA dosage	75-1200 mg/d	325 mg per every other day	100 mg per every other day
Duration of follow up (yr)	≥ 20	10	10
Relative risk of CRC over follow up (HR)	0.76 (95%CI: 0.60-0.96)	1.03 (95%CI: 0.83-1.28)	0.97 (95%CI: 0.77-0.24)

Comparison of findings from meta-analysis performed by Rothwell et al[13] and incidence data of Physician’s Health Study and Women’s Health Study studies[13,15,16]. CRC: Colorectal cancer; ASA: Aspirin.

Table 4 Clinical effects of aspirin in incidence of sporadic colorectal adenomas (clinical trials)

Study	Patients	Treatment	RR (95%CI)
AFPPS trial	Patients with a recent history of histologically documented (removed) adenomas	ASA (81 or 325 mg/d) or folic acid (1 mg/d) or placebo for 2.7 years	Any adenoma 0.81 (0.69-0.96), ASA 81mg vs non ASA 0.96 (0.81-1.13), ASA 325 mg vs non ASA Advanced lesion 0.59 (0.38-0.92), ASA 81 mg vs non ASA 0.83 (0.55–1.23), ASA 325 mg vs non ASA
CAPS trial	Patients with a histologically documented colon or rectal cancer with a low risk of recurrent disease	ASA 325 mg/d or placebo for 2.6 years	0.65 (0.46-0.91)
APACC trial	Patients with a history of colorectal adenomas	ASA 160 or 300 mg/d or placebo for 1 and 4 years	0.73 (0.52-1.04) for both doses, after 1 year 0.96 (0.75-1.22), for both doses, after 4 years
ukCAP trial	Patients with an adenoma removed in the 6 mo before recruitment	ASA (300 mg/d) plus placebo or ASA plus folic acid (0.5 mg/d) or folic acid plus placebo or double placebo for about 2.6 years	Any adenoma 0.79 (0.63-0.99), ASA vs non ASA, Advanced adenoma 0.63 (0.43-0.91), ASA vs non ASA
J-CAPP trial	Patients with previous sporadic colorectal tumors	ASA 100 mg/d or placebo for 2 years	Ongoing

ASA: Aspirin.

Table 5 Clinical effects of aspirin in high risk population (clinical trials)

Study	Patients	Treatment	RR or HR (95%CI)	Ref.
CAPP1 trial	FAP young patients (10 to 21 years of age)	ASA (600 mg/d) plus placebo or resistant starch (30 g daily) plus placebo or double placebo for 17 years	RR = 0.77 (0.54-1.10), ASA vs non ASA	[22]
CAPP2 trial	Hereditary non-polyposis colon cancer or HNPCC	ASA (600 mg/d) or ASA placebo or resistant starch (30 g daily) or starch placebo for up to 4 years	HR = 0.63 (0.35-1.13), for the entire post-randomization period (ASA vs placebo) HR = 0.41 (0.19-0.86), for ≥ 2 years of treatment (ASA vs placebo)	[23]
J-FAPP II trial	FAP patients (≥ 16 years of age)	Placebo vs enteric coated ASA (100 mg/d ) for 6-10 mo	Ongoing	[25]

ASA: Aspirin; FAP: Familial adenomatous polyposis.