Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA.
Department of Civil and Environmental Engineering, Tufts University School of Engineering, Medford, MA, USA.
JNCI Cancer Spectr. 2021 Apr 19;5(3). doi: 10.1093/jncics/pkab037. eCollection 2021 Jun.
Observational studies indicate that periodontal disease may increase the risk of colorectal, lung, and pancreatic cancers. Using a 2-sample Mendelian randomization (MR) analysis, we assessed whether a genetic predisposition index for periodontal disease was associated with colorectal, lung, or pancreatic cancer risks.
Our primary instrument included single nucleotide polymorphisms with strong genome-wide association study evidence for associations with chronic, aggressive, and/or severe periodontal disease (rs729876, rs1537415, rs2738058, rs12461706, rs16870060, rs2521634, rs3826782, and rs7762544). We used summary-level genetic data for colorectal cancer (n = 58 131 cases; Genetics and Epidemiology of Colorectal Cancer Consortium, Colon Cancer Family Registry, and Colorectal Transdisciplinary Study), lung cancer (n = 18 082 cases; International Lung Cancer Consortium), and pancreatic cancer (n = 9254 cases; Pancreatic Cancer Consortia). Four MR approaches were employed for this analysis: random-effects inverse-variance weighted (primary analyses), Mendelian Randomization-Pleiotropy RESidual Sum and Outlier, simple median, and weighted median. We conducted secondary analyses to determine if associations varied by cancer subtype (colorectal cancer location, lung cancer histology), sex (colorectal and pancreatic cancers), or smoking history (lung and pancreatic cancer). All statistical tests were 2-sided.
The genetic predisposition index for chronic or aggressive periodontitis was statistically significantly associated with a 3% increased risk of colorectal cancer (per unit increase in genetic index of periodontal disease; = .03), 3% increased risk of colon cancer ( = .02), 4% increased risk of proximal colon cancer ( = .01), and 3% increased risk of colorectal cancer among females ( = .04); however, it was not statistically significantly associated with the risk of lung cancer or pancreatic cancer, overall or within most subgroups.
Genetic predisposition to periodontitis may be associated with colorectal cancer risk. Further research should determine whether increased periodontitis prevention and increased cancer surveillance of patients with periodontitis is warranted.
观察性研究表明，牙周病可能会增加结直肠癌、肺癌和胰腺癌的风险。本研究采用两样本 Mendelian 随机化（MR）分析，评估牙周病遗传易感性指数与结直肠癌、肺癌或胰腺癌风险之间的关系。
本研究的主要工具包括与慢性、侵袭性和/或严重牙周病具有强全基因组关联研究证据的单核苷酸多态性(rs729876、rs1537415、rs2738058、rs12461706、rs16870060、rs2521634、rs3826782 和 rs7762544)。本研究使用了结直肠癌（n=58131 例；遗传学和结直肠癌流行病学联合会、结肠癌家族登记处和结直肠跨学科研究）、肺癌（n=18082 例；国际肺癌联合会）和胰腺癌（n=9254 例；胰腺癌联合会）的汇总水平遗传数据。本研究采用了四种 MR 方法：随机效应逆方差加权（主要分析）、Mendelian Randomization-Pleiotropy RESidual Sum and Outlier、简单中位数和加权中位数。本研究还进行了二次分析，以确定关联是否因癌症亚型（结直肠癌部位、肺癌组织学）、性别（结直肠癌和胰腺癌）或吸烟史（肺癌和胰腺癌）而异。所有统计检验均为双侧。
慢性或侵袭性牙周炎的遗传易感性指数与结直肠癌风险增加 3%（牙周病遗传指数每增加一个单位；=0.03）、结肠癌风险增加 3%（=0.02）、近端结肠癌风险增加 4%（=0.01）和女性结直肠癌风险增加 3%（=0.04）相关；然而，其与肺癌或胰腺癌风险之间总体上或在大多数亚组中均无统计学显著相关性。
牙周炎的遗传易感性可能与结直肠癌风险相关。进一步的研究应确定是否需要加强对牙周病患者的牙周病预防和癌症监测。
