Stanesby Oliver, Jenkins Mark
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.
Centre for Alcohol Policy Research, Department of Public Health, La Trobe University, Melbourne, VIC, Australia.
Eur J Hum Genet. 2017 Jun;25(7):832-838. doi: 10.1038/ejhg.2017.60. Epub 2017 May 10.
Given that colorectal cancer risk depends partly on inherited factors, screening program efficiency may be increased by incorporating genetic factors. We compared the efficiency of screening based on age and genetic risk in a simulated population. We simulated a population matching the size, age distribution and colorectal cancer incidence and mortality of Australia. We also simulated the distribution of genetic risk for colorectal cancer based on the expected number of inherited risk alleles of 45 single-nucleotide polymorphisms (SNPs) previously reported as associated with colorectal cancer. We compared the expected colorectal cancer deaths under three screening programs; age-based, genetic-based and combined age-based and genetic-based. The age-based program would prevent 25.4 deaths per 100 000 invited to screen, none of which would be under age 50; the genetic program would prevent 26.2 deaths per 100 000 invited to screen, 16 of which would be under age 50; and the combined program would prevent 24.4 deaths per 100 000 invited to screen, 16 of which would be under age 50. Genetic testing of 1.5 million 45-49 year olds would identify 91% of the people aged under 50 at sufficient risk to warrant screening, potentially saving 16 colorectal cancer deaths each year. Screening eligibility based on genetic risk profile for age is as efficient as eligibility based on age alone for preventing colorectal cancer mortality, but identifies an additional 7% of the population at sufficient risk to benefit from screening who would not normally be screened given they are aged under 50 years.
鉴于结直肠癌风险部分取决于遗传因素，纳入遗传因素可能会提高筛查项目的效率。我们在一个模拟人群中比较了基于年龄和遗传风险的筛查效率。我们模拟了一个与澳大利亚的规模、年龄分布以及结直肠癌发病率和死亡率相匹配的人群。我们还根据先前报道的与结直肠癌相关的45个单核苷酸多态性（SNP）的遗传风险等位基因预期数量，模拟了结直肠癌的遗传风险分布。我们比较了三种筛查项目下预期的结直肠癌死亡人数；基于年龄的、基于遗传的以及基于年龄和遗传相结合的。基于年龄的项目每10万名受邀筛查者中将预防25.4例死亡，其中没有一例是50岁以下的；基于遗传的项目每10万名受邀筛查者中将预防26.2例死亡，其中16例是50岁以下的；而综合项目每10万名受邀筛查者中将预防24.4例死亡，其中16例是50岁以下的。对150万45 - 49岁的人进行基因检测，将识别出91%的50岁以下具有足够风险值得筛查的人群，每年可能挽救16例结直肠癌死亡病例。基于年龄的遗传风险概况确定筛查资格在预防结直肠癌死亡率方面与仅基于年龄确定资格一样有效，但能识别出另外7%具有足够风险可从筛查中受益的人群，这些人通常因年龄在50岁以下而不会接受筛查。
