Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev
The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen
Ann Oncol. 2017 Jan 1;28(1):175-181. doi: 10.1093/annonc/mdw536.
We hypothesized that common breast cancer risk alleles are associated with incidences of breast cancer and other cancers in the general population, and identify low risk women among those invited for screening mammography.
About 35 441 individuals from the Danish general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0–2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer.
Breast cancer incidence in the 19 010 women was increased across allele sum quintiles (log-rank trend test; P = 1×10 − 12), but not incidence of other cancers (P = 0.41). Age- and study-adjusted hazard ratio for the fifth versus the first allele sum quintile was 1.82 (95% confidence interval; 1.53–2.18). Corresponding hazard ratios per allele were 1.04 (1.03–1.05) and 1.05 (1.02–1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year-old women, the starting age for screening mammography in Denmark, the average 5-year breast cancer risk was 1.5%, overall and 1.1%, 1.4%, 1.6%, 1.7%, 2.1%, for the first through fifth quintile, respectively. Based on age, nulliparity, familial history, and allele sum, 25% of women aged 50–69 years, and 94% of women aged 40–49 years, had absolute 5-year breast cancer risks ≤ 1.5%. Using polygenic risk score led to similar results.
Common breast cancer risk alleles are associated with incidence and mortality of breast cancer in the general population, but not with other cancers. After including breast cancer allele sum in risk assessment, 25% of women currently being offered screening mammography had an absolute 5-year risk below the cutoff of average risk for a 50-year-old woman.
我们假设常见的乳腺癌风险等位基因与普通人群中乳腺癌和其他癌症的发病率有关，并在接受乳房 X 光筛查的女性中确定低风险女性。
大约 35441 名丹麦普通人群的个体在接受血液采样后，在丹麦健康登记处进行了长达 21 年的随访。在对 72 个乳腺癌风险位点进行基因分型后，计算了每个个体的等位基因总和。我们使用简单的等位基因总和，而不是传统的多基因风险评分，因为它更有可能检测到与其他终点风险相关的关联，而不仅仅是乳腺癌。
在 19010 名女性中，乳腺癌发病率随等位基因总和五分位数的增加而升高（对数秩检验趋势检验；P=1×10-12），但其他癌症的发病率没有增加（P=0.41）。第五五分位与第一五分位相比，年龄和研究调整后的风险比为 1.82（95%置信区间，1.53-2.18）。每个等位基因的相应风险比为乳腺癌发病率和死亡率的 1.04（1.03-1.05）和 1.05（1.02-1.08），在各种危险因素之间相似。在 50 岁开始进行丹麦乳房 X 光筛查的女性中，总体和第 1 至第 5 五分位的平均 5 年乳腺癌风险分别为 1.5%、1.1%、1.4%、1.6%、1.7%和 2.1%。基于年龄、未婚、家族史和等位基因总和，50-69 岁的女性中有 25%，40-49 岁的女性中有 94%，绝对 5 年乳腺癌风险≤1.5%。使用多基因风险评分会产生类似的结果。
常见的乳腺癌风险等位基因与普通人群中乳腺癌的发病率和死亡率有关，但与其他癌症无关。在风险评估中纳入乳腺癌等位基因总和后，目前接受乳房 X 光筛查的女性中有 25%的绝对 5 年风险低于 50 岁女性平均风险的截止值。
