, . 184: 340 (1998)

Ki-ras MUTATIONS IN ADENOMAS FROM CANCER-BEARING ANDCANCER-FREE BOWEL

We read with interest the paper by Morris et al.1reporting a higher incidence of Ki-ras oncogenemutations in villous or tubulovillous adenomas removedfrom cancer-bearing bowel as opposed to cancer-freebowel. Our calculation of the odds ratio for their data is3·125. They found the higher percentage of mutations inadenomas from cancer-bearing bowel to be largelyattributable to adenomas recovered from patients over70 years of age.We have evaluated a cohort of patients with sporadic

colorectal polyps and cancer. All patients had hadcomplete colonoscopies, thus ensuring proper identi-fication as to cancer-bearing or cancer-free bowel. Weanalysed 188 adenomas and 52 carcinomas for muta-tions in codons 12/13 of the Ki-ras gene using single-strand conformational polymorphism polyacrylamideelectrophoresis. We derived the odds ratio and 95 percent confidence intervals and used a two-sided chi-squaretest for the level of significance. This is a more conserv-ative test than the one-sided test used by Morris et al.For all adenomas, we found a 2·6-fold increased risk

for a mutation in adenomas from cancer-bearing bowelcompared with adenomas from cancer-free bowel, whenadjusted for histology, P<0·02 (Table I). When wecontrolled for age less than or greater than 70 years, wefound a 3·2-fold increased risk for Ki-ras mutation in

villous and tubulovillous adenomas from cancer-bearingbowel, compared with similar adenomas from cancer-free bowel. However, the P value was only borderlinesignificant, with P<0·06, reflecting the small number ofpatients.Our data therefore support those reported by Morris

et al. We agree with the authors that the cause orcauses of the higher frequency remain speculative.Those patients with polyps and cancer may have hadgreater exposure to dietary carcinogens or they mayhave increased susceptibility to the development ofmutations. Studies of multiple lesions within a givenfamily may help to address this question.

N. P Z1, M S-S1, D. T B2

1Departments of Medicine and PathologySaint Barnabas Medical CenterLivingston, NJ 07039, U.S.A.2Genetic Epidemiology Unit

Saint James University HospitalLeeds, U.K.

REFERENCE1. Morris R, Curtis L, Romanowski R, et al. Ki-ras mutations in adenomas:

a characteristic of cancer-bearing colorectal mucosa. J Pathol 1996; 180:357–363.

AUTHORS’ REPLY

We are of course delighted that the substantialstudy of Dr Bishop and his colleagues confirms ourobservation.

A. H. W

Table I—Incidence of Ki-ras mutations

Source

Cancer-free bowel Cancer-bearing bowel

Odds ratioTotal studied Mutations (%) Total studied Mutations (%)

All adenomas 111 22 (20%) 77 25 (32%)Tubular adenomas 80 7 (9%) 57 10 (17·5%)Villous adenomas 31 15 (48%) 20 15 (75%)

2·6*(1·2,5·6)

Patient’s age (years)<70 18 9 (50%) 11 8 (72%)>70 13 6 (46%) 9 U7 (77%)

3·2†(0·9,16·7)

*Odds ratio adjusted for histology, P<0·02.†Odds ratio adjusted for age, P<0·06.

? 1998 John Wiley & Sons, Ltd.