CPR：口腔病变发展成癌症的风险识别

一项最新研究发现一组分子标记可以帮助医生确定哪些低等级的口腔黏膜癌前病变患者会发展演变成口腔癌，相关研究论文发表在Cancer Prevention Research杂志上。

Miriam Rosin博士说：该研究结果有助于帮助我们认识到不是每个低等级口腔癌前病变的人都会发展罹患癌症。不过，该研究结果能便于临床医生更好地了解哪些患者需要更加密切的跟进关注。

口腔癌是一个全球性的公共卫生问题，每年在世界各地有近30万新发病例。之前，许多这些癌症癌症都出现了癌前病变现象。严重的癌前病变与癌症罹患风险应早已被证实确定的。然而，其中一个巨大的挑战就是如何区分低度病变是不是最有可能发展为癌症。

在2000年，Rosin和他的同事们收集了那些口腔黏膜癌前病变发展到癌症的患者样本，根据他们的DNA差异，将患者分为低风险或高风险类别，研究人员能够正确地区分出哪些人更容易发展为癌患者。

他们分析了296例有轻度或中度口腔异常增生的患者，随后经过多年的BC口腔活检测试，结果发现那些归类为高风险的患者发展罹患口腔癌的风险有增加近23倍。

接着被称为杂合性丢失的两个额外的DNA分子风险标记物被用来更好地区别病人罹患癌症的风险。他们使用前瞻性研究中的疾病样本，并将患者分为分为低、中、高风险组。

Rosin说：相比较于低风险的患者来说、中等风险的患者罹患口腔癌的风险增加了11倍，高风险组的患者罹患口腔癌的风险增加了52倍。

在归类为低风险的患者中，只有3.1％的人在五年内可能会发展得癌症疾病。相比之下，中等风险的患者5年内有16.3％的可能性会得癌症，而高风险的患者5年有63.1％的可能性的癌症。

Rosin表示：识别早期病变可能便于临床医生更早有机会介入治疗，可能有助于在低风险的情况下就防止癌症的发生。

编译自：Researchers identified markers that predict progression of oral lesions to cancer

doi:10.1158/1940-6207.CAPR-12-0173
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Loss of Heterozygosity (LOH) Profiles—Validated Risk Predictors for Progression to Oral Cancer

Lewei Zhang4,5, Catherine F. Poh1,2,4,5, Michele Williams2,4, Denise M. Laronde1,4, Ken Berean5, Pamela J. Gardner3, Huijun Jiang1, Lang Wu6, J. Jack Lee8, and Miriam P. Rosin1,7

A major barrier to oral cancer prevention has been the lack of validated risk predictors for oral premalignant lesions (OPL). In 2000, we proposed a loss of heterozygosity (LOH) risk model in a retrospective study. This paper validated the previously reported LOH profiles as risk predictors and developed refined models via the largest longitudinal study to date of low-grade OPLs from a population-based patient group. Analysis involved a prospective cohort of 296 patients with primary mild/moderate oral dysplasia enrolled in the Oral Cancer Prediction Longitudinal Study. LOH status was determined in these OPLs. Patients were classified into high-risk or low-risk profiles to validate the 2000 model. Risk models were refined using recursive partitioning and Cox regression analyses. The prospective cohort validated that the high-risk lesions (3p and/or 9p LOH) had a 22.6-fold increase in risk (P = 0.002) compared with low-risk lesions (3p and 9p retention). Addition of another 2 markers (loci on 4q/17p) further improved the risk prediction, with five-year progression rates of 3.1%, 16.3%, and 63.1% for the low-, intermediate-, and high-risk lesions, respectively. Compared with the low-risk group, intermediate- and high-risk groups had 11.6-fold and 52.1-fold increase in risk (P < 0.001). LOH profiles as risk predictors in the refined model were validated in the retrospective cohort. Multicovariate analysis with clinical features showed LOH models to be the most significant predictors of progression. LOH profiles can reliably differentiate progression risk for OPLs. Potential uses include increasing surveillance for patients with elevated risk, improving target intervention for high-risk patients while sparing a large number of low-risk patients from needless screening and treatment.