Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome.
BACKGROUND
Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect on the colon.


METHODS
In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome.


RESULTS
Among 1071 persons in 43 centers, 62 were ineligible to participate in the study, 72 did not enter the study, and 191 withdrew from the study. These three categories were equally distributed across the study groups. Over a mean period of 29 months (range, 7 to 74), colonic adenoma or carcinoma developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant differences between the two groups with respect to the development of advanced neoplasia (7.4% and 9.9%, respectively; P=0.33). Among the 727 participants receiving resistant starch or placebo, neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18.4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed.


CONCLUSIONS
The use of aspirin, resistant starch, or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.)
Burn
John
J
Institute of Human Genetics, Newcastle University, International Centre for Life, Central Pkwy., Newcastle upon Tyne NE1 3BZ, United Kingdom. john.burn@ncl.ac.uk.
Bishop
D Timothy
DT
Mecklin
Jukka-Pekka
JP
Macrae
Finlay
F
Möslein
Gabriela
G
Olschwang
Sylviane
S
Bisgaard
Marie-Luise
ML
Ramesar
Raj
R
Eccles
Diana
D
Maher
Eamonn R
ER
Bertario
Lucio
L
Jarvinen
Heikki J
HJ
Lindblom
Annika
A
Evans
D Gareth
DG
Lubinski
Jan
J
Morrison
Patrick J
PJ
Ho
Judy W C
JW
Vasen
Hans F A
HF
Side
Lucy
L
Thomas
Huw J W
HJ
Scott
Rodney J
RJ
Dunlop
Malcolm
M
Barker
Gail
G
Elliott
Faye
F
Jass
Jeremy R
JR
Fodde
Ricardo
R
Lynch
Henry T
HT
Mathers
John C
JC
D000236:Adenoma / Q000453:epidemiology / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000453:epidemiology / Q000517:prevention & control*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000188:drug therapy* / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D013213:Starch / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
D013213:Starch; D001241:Aspirin