Narimatsu H, Iwasaki H, Nakayama F, Ikehara Y, Kudo T, Nishihara S, Sugano K, Okura H, Fujita S, Hirohashi S
Division of Cell Biology, Institute of Life Science, Soka University, Hachioji, Toyko, Japan.
Cancer Res. 1998 Feb 1;58(3):512-8.
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, le/le and se/se; group 8, le/le and Se/se; and group 9, le/le and Se/Se. The group 1 individuals, having homozygous inactive Se alleles (se/se) and homozygous active Le alleles (Le/Le), 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 le/le genotype (groups 7, 8, and 9) had completely negative CA19-9 values, i.e., under 1.0 unit/ml, irrespective of the Se genotype. Group 7 individuals (le/le and se/se) showed a higher mean DU-PAN-2 value than did individuals in other groups. The Le-negative individuals in groups 8 and 9 also showed a higher mean DU-PAN-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 CA19-9 and DU-PAN-2 values were measured before surgical resection. All 15 Le-negative patients (le/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.
在400名正常个体中研究了分泌型（Se）和Lewis（Le）基因剂量对血清CA19-9和DU-PAN-2水平的影响。结果清楚地表明，Se基因剂量对CA19-9和DU-PAN-2值均有负面影响，而Le基因剂量对CA19-9值有正面影响，对DU-PAN-2值有负面影响。这400名正常个体根据其Le和Se基因型被分为9组，如下：第1组，Le/Le和se/se；第2组，Le/le和se/se；第3组，Le/Le和Se/se；第4组，Le/le和Se/se；第5组，Le/Le和Se/Se；第6组，Le/le和Se/Se；第7组，le/le和se/se；第8组，le/le和Se/se；第9组，le/le和Se/Se。第1组个体具有纯合无活性Se等位基因（se/se）和纯合活性Le等位基因（Le/Le），其平均CA19-9值最高。CA19-9值明显从第1组的高值到第9组的低值变化。所有具有le/le基因型的Le阴性个体（第7、8和9组）的CA19-9值均完全为阴性，即低于1.0单位/毫升，与Se基因型无关。第7组个体（le/le和se/se）的平均DU-PAN-2值高于其他组个体。第8组和第9组的Le阴性个体的平均DU-PAN-2值也高于第1-6组的Le阳性个体。我们建议将本研究确定的经修订的Le和Se基因型依赖性CA19-9和DU-PAN-2的阳性/阴性临界值应用于更准确的癌症诊断。还检查了168例结直肠癌患者的Le和Se基因型，并在手术切除前测量了CA19-9和DU-PAN-2值。所有15例Le阴性（le/le）结直肠癌患者的CA19-9值再次检测不到，即低于1.0单位/毫升，但其中许多患者的DU-PAN-2值呈高度阳性。相比之下，许多Le阳性患者（Le/Le或Le/le）的CA19-9值为阳性，而其中很少有人的DU-PAN-2值为阳性。对于Le阳性患者，CA19-9测量比DU-PAN-2测量更有用，但对Le阴性患者则无用。对于癌症诊断，应在Le阴性患者中进行DU-PAN-2测量。
