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男性健康专业人员的牙周疾病、牙齿脱落与癌症风险:一项前瞻性队列研究。

Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study.

作者信息

Michaud Dominique S, Liu Yan, Meyer Mara, Giovannucci Edward, Joshipura Kaumudi

机构信息

Department of Epidemiology and Public Health, Imperial College London, London, UK.

出版信息

Lancet Oncol. 2008 Jun;9(6):550-8. doi: 10.1016/S1470-2045(08)70106-2. Epub 2008 May 5.

Abstract

BACKGROUND

Studies suggest that tooth loss and periodontal disease might increase the risk of developing various cancers; however, smoking might have confounded the reported associations. We aimed to assess whether periodontal disease or tooth loss is associated with cancer risk.

METHODS

The analysis was done in a prospective study (the Health Professionals Follow-Up Study [HPFS]), which was initiated in 1986 when US male health professionals aged 40-75 years responded to questionnaires posted by the Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA. In addition to the baseline questionnaires, follow-up questionnaires were posted to all living participants every 2 years and dietary questionnaires every 4 years. At baseline, participants were asked whether they had a history of periodontal disease with bone loss. Participants also reported number of natural teeth at baseline and any tooth loss during the previous 2 years was reported on the follow-up questionnaires. Smoking status and history of smoking were obtained at baseline and in all subsequent questionnaires. Additionally at baseline, participants reported their mean frequency of food intake over the previous year on a 131-item semiquantitative food-frequency questionnaire. Participants reported any new cancer diagnosis on the follow-up questionnaires. Endpoints for this study were risk of total cancer and individual cancers with more than 100 cases. Multivariate hazard ratios (HRs) and 95% CIs were calculated by use of Cox proportional hazard models according to periodontal disease status and number of teeth at baseline.

FINDINGS

In the main analyses, 48 375 men with median follow-up of 17.7 years (1986 to Jan 31, 2004) were eligible after excluding participants diagnosed with cancer before 1986 (other than non-melanoma skin cancer, n=2076) and those with missing data on periodontal disease (n=1078). 5720 incident cancer cases were documented (excluding non-melanoma skin cancer and non-aggressive prostate cancer). The five most common cancers were colorectal (n=1043), melanoma of the skin (n=698), lung (n=678), bladder (n=543), and advanced prostate (n=541). After adjusting for known risk factors, including detailed smoking history and dietary factors, participants with a history of periodontal disease had an increased risk of total cancer (HR 1.14 [95% CI 1.07-1.22]) compared with those with no history of periodontal disease. By cancer site, significant associations for those with a history of periodontal disease were noted for lung (1.36 [1.15-1.60]), kidney (1.49 [1.12-1.97]), pancreas (1.54 [1.16-2.04]; findings previously published), and haematological cancers (1.30 [1.11-1.53]). Fewer teeth at baseline (0-16) was associated with an increase in risk of lung cancer (1.70 [1.37-2.11]) for those with 0-16 teeth versus those with 25-32 teeth. In never-smokers, periodontal disease was associated with significant increases in total (1.21 [1.06-1.39]) and haematological cancers (1.35 [1.01-1.81]). By contrast, no association was noted for lung cancer (0.96 [0.46-1.98]).

INTERPRETATION

Periodontal disease was associated with a small, but significant, increase in overall cancer risk, which persisted in never-smokers. The associations recorded for lung cancer are probably because of residual confounding by smoking. The increased risks noted for haematological, kidney, and pancreatic cancers need confirmation, but suggest that periodontal disease might be a marker of a susceptible immune system or might directly affect cancer risk.

摘要

背景

研究表明,牙齿脱落和牙周疾病可能会增加患各种癌症的风险;然而,吸烟可能混淆了所报告的关联。我们旨在评估牙周疾病或牙齿脱落是否与癌症风险相关。

方法

该分析在一项前瞻性研究(健康专业人员随访研究[HPFS])中进行,该研究始于1986年,当时美国40 - 75岁的男性健康专业人员回复了美国马萨诸塞州波士顿哈佛大学公共卫生学院营养系发布的问卷。除了基线问卷外,每2年向所有在世参与者发放随访问卷,每4年发放饮食问卷。在基线时,询问参与者是否有伴有骨质流失的牙周疾病史。参与者还报告了基线时的天然牙数量,并且在随访问卷中报告了前两年内的任何牙齿脱落情况。在基线及所有后续问卷中获取吸烟状况和吸烟史。此外,在基线时,参与者通过一份包含131个项目的半定量食物频率问卷报告了他们前一年的平均食物摄入频率。参与者在随访问卷中报告任何新的癌症诊断。本研究的终点是总癌症风险以及病例数超过100例的个体癌症风险。根据牙周疾病状况和基线时的牙齿数量,使用Cox比例风险模型计算多变量风险比(HR)和95%置信区间(CI)。

结果

在主要分析中,排除1986年之前被诊断患有癌症(非黑色素瘤皮肤癌除外,n = 2076)以及牙周疾病数据缺失的参与者(n = 1078)后,48375名男性符合条件,他们的中位随访时间为17.7年(1986年至2004年1月31日)。记录了5720例新发癌症病例(排除非黑色素瘤皮肤癌和非侵袭性前列腺癌)。五种最常见的癌症是结直肠癌(n = 1043)、皮肤黑色素瘤(n = 698)、肺癌(n = 678)、膀胱癌(n = 543)和晚期前列腺癌(n = 541)。在调整了包括详细吸烟史和饮食因素在内的已知风险因素后,有牙周疾病史的参与者与无牙周疾病史的参与者相比,患总癌症的风险增加(HR 1.14 [95% CI 1.07 - 1.22])。按癌症部位划分,有牙周疾病史的参与者在肺癌(1.36 [1.15 - 1.60])、肾癌(1.49 [1.12 - 1.97])、胰腺癌(1.54 [1.16 - 2.04];此前已发表的结果)和血液系统癌症(1.30 [1.11 - 1.53])方面存在显著关联。与有25 - 32颗牙齿的参与者相比,基线时牙齿较少(0 - 16颗)的参与者患肺癌的风险增加(1.70 [1.37 - 2.11])。在从不吸烟者中,牙周疾病与总癌症(1.21 [1.06 - 1.39])和血液系统癌症(1.35 [1.01 - 1.81])的显著增加相关。相比之下,肺癌未发现关联(0.96 [0.46 - 1.98])。

解读

牙周疾病与总体癌症风险的小幅但显著增加相关,这种关联在从不吸烟者中持续存在。记录的肺癌关联可能是由于吸烟的残余混杂因素。血液系统、肾脏和胰腺癌风险增加需要进一步证实,但表明牙周疾病可能是易感免疫系统的一个标志,或者可能直接影响癌症风险。

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