Lewis and Secretor Gene Dosages Affect CA19-9 and DU-PAN-2 Serum Levels in Normal Individuals and Colorectal Cancer Patients1

The effect of doses of the secretor (Se) and Lewis (Le} genes on the serum levels of CA19-9 and DU-PAN-2 was investigated in 400 normal individuals. It was clearly demonstrated that the Se gene dosage negatively affected both the CA19-9 and DU-PAN-2 values, whereas the Le gene dosage positively affected the CA19-9 value and negatively affected the DU-PAN-2 value. The 400 normal individuals were separated into nine groups by their Le and Se genotypes, as follows: group 1, Le/Le and se/se; group 2, Le/le and se/se; group 3, Le/Le and Se/se; group 4, Le/le and Se/se; group 5, Le/Le and Se/Se; group 6, Le/le and Se/Se; group 7, Ielle and se/se; group 8, Ielle and Se/se; and group 9, /(•//<• and Se/Se. The group 1 individuals, having homozygous inactive V alÃ-eles(se/se] and homozygous active Le alÃ-eles (Le/Lei, exhibited the highest mean CA19-9 value. The CA19-9 value clearly ranged from a high in group 1 to a low in group 9. All of the Le-negative individuals who had the Ielle genotype (groups 7,8, and 9) had completely negative CAI9-9 values, i.e., under 1.0 unit/ml, irrespective of the Se genotype, (ìroup7 individuals (Ielle and se/se) showed a higher mean DU-PAN-2 value than did individuals in other groups. The Lenegative individuals in groups 8 and 9 also showed a higher mean DUPAN-2 value than did the Le-positive individuals in groups 1-6. We recommend that the revised Le and Se genotype-dependent positive/negative cutoff values for CA19-9 and DU-PAN-2, determined in this study, be applied for more accurate cancer diagnoses. The Le and Se genotypes of 168 patients with colorectal cancer were also examined, and the CAI9-9 and DU-PAN-2 values were measured before surgical resection. All 15 Le-negative patients ile/le) with colorectal cancer again showed undetectable CA19-9 values, i.e., under 1.0 unit/ml, but many of them exhibited highly positive DU-PAN-2 values. In contrast, many of the Le-positive patients (Le/Le or Le/le} had positive CA19-9 values, whereas very few of them exhibited positive DU-PAN-2 values. CA19-9 measurement is more useful than is DU-PAN-2 measurement for Le-positive patients, but it is not useful for Le-negative ones. DU-PAN-2 measurement should be performed in Le-negative patients for cancer diagnosis.