Detecting K-ras mutations in stool from fecal occult blood test cards in multiphasic screening for colorectal cancer.
Detecting K-ras mutations in stool from fecal occult blood test cards in multiphasic screening for colorectal cancer.
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DOI：
10.1016/j.canlet.2007.01.023
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发表时间：
2007-08
期刊：
影响因子：
9.7
通讯作者：
G. Rennert;D. Kislitsin;D. Brenner;H. Rennert;Z. Lev
中科院分区：
文献类型：
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作者：
G. Rennert;D. Kislitsin;D. Brenner;H. Rennert;Z. Lev
粪便潜血试验（FOBT）被证明是降低结直肠癌死亡率的有效方法，但阳性预测值（PPV）相对较低。本研究评价了从FOBT卡中检测粪便DNA中K-ras突变的能力，并提高了筛查过程的PPV。205个连续的阳性FOBT卡和38个阴性卡的任意样本，从人口为基础的筛选程序。用等位基因特异性杂交法检测FOBT卡粪便中K-ras基因突变。从87.2%的卡片中成功扩增DNA。在130例FOBT和可扩增DNA阳性的病例中，检出恶性肿瘤23例，腺瘤25例。在34.8%的恶性肿瘤中，检测到K-ras突变。恶性肿瘤的PPV从17.7%（所有阳性卡）增加到60.0%（如果卡具有4个或更多字段为阳性且K-ras为阳性）（RR=2.66，95%CI：1.2-6.1）。从阳性FOBT卡粪便中提取的DNA中检测K-ras突变是可行的。从基于FOBT的粪便样本中连续检测癌症相关的遗传标记可能有助于在基于FOBT的筛查过程中区分真阳性和假阳性。
Fecal occult blood testing (FOBT) is proven an efficient way of reducing mortality from colorectal cancer but has a relatively low positive predictive value (PPV). This study evaluated the ability to detect K-ras mutations in stool DNA from FOBT cards and to improve the PPV of the screening process. Two hundred and five consecutive positive FOBT cards and an arbitrary sample of 38 negative cards from a population-based screening program were included. K-ras mutations in FOBT card stool were sought using allele-specific hybridization. DNA was successfully amplified from 87.2% of cards. In 130 cases with positive FOBT and amplifiable DNA 23 malignancies and 25 adenomas were detected. In 34.8% of the malignancies, a mutation in K-ras was detected. The PPV for malignancies increased from 17.7% (all positive cards) to 60.0% if cards with four or more fields were positive and K-ras was positive (RR=2.66, 95% CI: 1.2–6.1). Testing for K-ras mutations in DNA extracted from stool from positive FOBT cards is feasible. Sequential detection of cancer-associated genetic markers from FOBT-based stool samples may potentially help separate true from false positives in a FOBT-based screening process.