染色体信息可预测口腔癌风险
2012-08-26 11:09:05   来源： 丁香园   作者：  评论：0 点击：

染色体信息可预测口腔癌风险

Chromosomes Predict Oral Cancer Risk

A pattern of chromosomal changes can predict which patients withpremalignant oral lesions will go on to cancer, researchers reported.研究人员报道：染色体变化形式可以预测患者癌变前口腔病损是否会转为癌症。
Patients with a loss of heterozygosity (LOH) onthe short arms of chromosomes 9 and 17 and the long arm of chromosome 4 have a52-fold increase in the risk of oral squamous cell carcinoma compared withthose who retain the heterozygous copy on all three, according to Miriam Rosin,PhD, of the BC Cancer Agency in Vancouver, and colleagues.温哥华BC癌症研究中心的Miriam Rosin博士（PhD）与他的同事发现：在9号，17号染色体短臂以及4号染色体长臂杂合性缺失的患者相比那些保留了杂合性的人来说患口腔鳞状细胞癌的 风险为52倍。
The finding, from a prospective study of 296patients with mild or moderate oral dysplasia, "holds great promise forimproving the clinical management of oral precancers," Rosin andcolleagues argued online in Cancer Prevention Research.通过对296名患有轻微或中度口腔畸形的患者的一项前瞻性研究，结果“对于提升临床上处理癌症前期的手段大有前途”。癌症预防研究中心 的Rosin与同事在网上如是说。
"The results of our study should help tobuild awareness that not everyone with a low-grade oral premalignant lesionwill progress to cancer," Rosin said in a statement. "However, theyshould also begin to give clinicians a better idea of which patients needcloser follow-up."“我们研究的结果将建立并不是所有具有口腔癌前低级病损的人都会发展为癌症这样一个认识。”Rosin说，“然而，他们同样需要给 临床医生关于对何种患者做更多随访的建议。”
The prospective study is a follow-up to aretrospective analysis published in 2000, in which Rosin and colleagues showedthat loss of heterozygosity on the short arms of chromosomes 3 and 9 wasassociated with progression of oral lesions.这项前瞻性研究是对2000年发表的一项回顾性研究的后续，在其中Rosin和他的同事发现染色体3号和9号短臂杂合性的丢失与病损癌变 相关。
In the current analysis, they refined the modeland showed that chromosome 3 is less important than combinations of the otherthree -- 4, 9, and 17 -- with chromosome 9 playing a central role.在如今的分析中，他们精确了模型并发现3号染色体不如其它三个染色体的结合更为重要，即4，9和17，其中9号最为重要。
The "extraordinarily well-done andwell-analyzed studies (are) a major advance," commented Webster Cavenee,PhD, of the University of California San Diego in La Jolla, Calif.加利福尼亚州拉荷亚加州大学圣地亚哥分校的Webster Cavenee,博士（PhD）说：“这项非凡的，很好实施和分析的研究，是一个重大的进步。”
Cavenee, one of the researchers who in 1983 firstidentified loss of heterozygosity as a cause of cancer, argued that suchgenetic changes can in principle be used to predict progression.于1983年首批发现杂合性缺失导致癌症的研究人员之一Cavenee表示这样的基因改变在原则上可以预测癌症发展。
The study by Rosin and colleagues is an"incisive test" of that idea, Cavenee wrote in an accompanyingperspective article.Rosin和他同事的工作是对这种想法的一项“深刻的测试”，Cavenee在一篇相关的分析文章中写道。
LOH is usually defined as the loss of normalfunction of one copy of a gene in which the other copy was already inactivated.杂合性丢失是基因一个拷贝的正常功能丢失，同时另一个拷贝已经失活。
Rosin and colleagues used the prospective cohortfirst to validate their retrospective model in which LOH on the short arms ofchromosomes 3 and 9 was associated with an increased risk of cancer, whileretention of heterozygosity was not.Rosin及其同事通过前瞻性群组确定了回顾性模型中3，9号染色体短臂的丢失增加了癌症的风险，而保留了杂合性的则不会。
Only 1 of every 100 lesions with the low-riskpattern progressed, but 39 of the 40 patients with LOH on both chromosomesprogressed, they reported, and the high-risk pattern was associated with a22.6-fold increase in the risk of progression.在低风险人群中，100名患者中仅有一名发展为癌症，而在杂合性缺失人群中40名中有39名发展为癌症。在高风险人群中，发展成 为癌症的几率增加了22.6倍。
Analysis suggested that LOH on chromosome 3 didnot play a significant role, however, so the researchers conducted a recursivepartitioning study on seven chromosomes in which LOH might play a role.分析显示3号染色体的杂合性丢失并不是非常重要，从而，研究人员对7个杂合性缺失可能发挥作用的染色体进行了递归拆分研究。
That analysis suggested that patients without LOHon chromosome 9 would be at low risk, those with LOH on chromosome 9 and one ofchromosomes 4 and 17 would be at intermediate risk, while those with LOH on allthree would be at high risk.分析结果表明9号染色体无杂合性缺失的患者风险较低，9号染色体有杂合性缺失，4和17号染色体中有一个有杂合性缺失的患者为中度风险，而三条 染色体均为杂合性缺失的为高度风险。
In the prospective cohort, 46.8% fell into thelow-risk category, 43.2% were intermediate, and 10.1% were high-risk, theyreported.在前瞻性群组中，46.8%的人为低风险，43.2%的人为中度风险，10.1%的人为高度风险。
Five-year progression rates were 3.1% for those atlow risk, 16.3% for those at intermediate risk, and 63.1% for those in thehigh-risk group.低风险的5年癌变率为3.1%，中度风险为16.3%，而高度风险为63.1%。
Compared with low-risk lesions:与低风险人群相比:
The hazard ratio for intermediate-risk lesions was11.6 (95% CI 2.7 to 49.9, P=0.001)The hazard ratio for high-risk was 52.1 (95% CI11.8 to 230.6, P<0.001)The finding "means that two out of everythree high-risk cases are progressing," Rosin said. "Identifyingwhich early lesions are more likely to progress may give clinicians a chance tointervene in high-risk cases and may help to prevent unnecessary treatment inlow-risk cases."中度风险病损的风险比为11.6%（95% CI 2.7 to 49.9, P=0.001）

高风险病损风险比为52.1%（95% CI 11.8 to 230.6, P<0.001）

结果“意味着高风险人群中每三个有两个癌症都在发展，”Rosin说，“确定何种病损更有可能癌变将帮助临床医生提早干预高风险人群并可以减少低风险人群中不必要的治疗开销。”
The researchers got similar results when they usedthe new model to recalculate risk groups and progression in the originalretrospective cohort and then in the two cohorts.研究人员在原有回顾组以及两个组中通过新模型重新计算风险和癌变概率得出了类似的结果。
For example, in the combined groups, 5-yearprogression rates were 4.8%, 22.9%, and 65.4%, respectively, in the low-,intermediate-, and high-risk groups.比如说，在混合组中，5年癌变率在低，中，高风险人群中分别为4.8%, 22.9%和 65.4%。
And in the low-risk group, no patient developedcancer during a median follow-up of 44.6 months.在低风险人群中，平均44.6的随访中，没有患者患癌症。
The study is "an important next step" indeveloping LOH profiles that pick out those at high risk for cancer, arguedMark Lingen, DDS, PhD, of the University of Chicago Medical Center in Chicago,and Eva Szabo, MD, of the National Cancer Institute in Bethesda, Md.这项研究是通过描绘杂合性缺失来评估癌症风险“重要的下一步”，芝加哥大学医学中心的Mark Lingen博士以及美国国家癌症中心的Eva Szabo博士说道。
In a second perspective article, they said thefindings have "direct implications for standard care in the communitysetting, identifying low-risk individuals who are not in need of aggressive monitoringor treatment."

在第二篇观念性论著中，他们提到这项发现“可以为群体设置以及标准治疗提供直接提示，并能够帮助确定低风险人群以避免过度医疗。”