Microsatellite instability (MSI) occurs in approximately 15% of colon tumor
s, Other than relatively rare mutations in mismatch repair genes, the cause
s of MSI are not generally known. The purpose of this study was to determin
e if dietary intake of nutrients previously reported as being associated wi
th colon cancer relate specifically to the MSI disease pathway. Data from a
population-based case-control study of adenocarcinoma of the colon were us
ed to evaluate associations between dietary intake and MSI, Participants we
re between 30 and 79 years of age at time of diagnosis and included both me
n and women. Dietary intake data were obtained from a computerized diet his
tory questionnaire. MSI was evaluated in several ways: by a panel of 10 tet
ranucleotide repeats, and by 2 mononucleotide repeats, BAT-26 and TGF beta
RII, A total of 1,510 cases had valid study data and tumor DNA on which we
were able to obtain MSI statue. Cases with and without MSI were compared wi
th dietary data reported by 2,410 population-based controls to determine di
etary associations that may be different for these 2 subsets of cases. We c
ompared dietary intake for cases with and without MSI to further determine
associations that are specific to the MSI disease pathway, When comparing M
SI+ to MSI- tumors we observed that: long-term alcohol consumption, especia
lly intake of liquor, increased the probability of having a tumor with MSI
[odds ratio (OR) for MSI+ vs. MSI- tumors for alcohol 1.6, 95% confidence i
nterval (CI) 1.0-2.5; OR for liquor 1.6, 95% CI 1.1-2.4], The likelihood of
having MSI in the tumor from the combined effects of high alcohol consumpt
ion and smoking cigarettes showed a 70% excess in risk from the additive mo
del. There were some suggestions that high intakes of refined grain might a
lso be associated with MSI+ tumors, although associations were less consist
ent. Risk estimates for moot: other dietary factors did not differ substant
ially by MSI status. Data from this large population-based case-control stu
dy of colon cancer indicate that alcohol consumption. especially consumptio
n of liquor, may increase the odds of an MSI+ tumor. Most other dietary fac
tors do not appear operate exclusively in the MSI+ disease pathway, (C) 200
1 Wiley-Liss. Inc.