Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
Ann Oncol. 2022 Jul;33(7):693-701. doi: 10.1016/j.annonc.2022.03.276. Epub 2022 Apr 6.
Pancreatic cancer presents as advanced disease in >80% of patients; yet, appropriate ages to consider prevention and early detection strategies are poorly defined. We investigated age-specific associations and attributable risks of pancreatic cancer for established modifiable and non-modifiable risk factors.
We included 167 483 participants from two prospective US cohort studies with 1190 incident cases of pancreatic cancer during >30 years of follow-up; 5107 pancreatic cancer cases and 8845 control participants of European ancestry from a completed multicenter genome-wide association study (GWAS); and 248 893 pancreatic cancer cases documented in the US Surveillance, Epidemiology, and End Results (SEER) Program. Across different age categories, we investigated cigarette smoking, obesity, diabetes, height, and non-O blood group in the prospective cohorts; weighted polygenic risk score of 22 previously identified single nucleotide polymorphisms in the GWAS; and male sex and black race in the SEER Program.
In the prospective cohorts, all five risk factors were more strongly associated with pancreatic cancer risk among younger participants, with associations attenuated among those aged >70 years. The hazard ratios comparing participants with three to five risk factors with those with no risk factors were 9.24 [95% confidence interval (CI) 4.11-20.77] among those aged ≤60 years, 3.00 (95% CI 1.85-4.86) among those aged 61-70 years, and 1.46 (95% CI 1.10-1.94) among those aged >70 years (P = 3×10). These factors together were related to 65.6%, 49.7%, and 17.2% of incident pancreatic cancers in these age groups, respectively. In the GWAS and the SEER Program, the associations with the polygenic risk score, male sex, and black race were all stronger among younger individuals (P ≤0.01).
Established risk factors are more strongly associated with earlier-onset pancreatic cancer, emphasizing the importance of age at initiation for cancer prevention and control programs targeting this highly lethal malignancy.
超过 80%的胰腺癌患者在就诊时已处于晚期；然而，对于合适的年龄阶段，人们尚未明确应考虑采取预防和早期检测策略。我们研究了既定的可改变和不可改变的风险因素与胰腺癌之间的年龄特异性关联和归因风险。
我们纳入了两项前瞻性美国队列研究的 167483 名参与者，这些参与者在 30 多年的随访期间发生了 1190 例胰腺癌病例；来自一项已完成的多中心全基因组关联研究（GWAS）的 5107 例胰腺癌病例和 8845 例欧洲血统对照参与者；以及在美国监测、流行病学和最终结果（SEER）计划中记录的 248893 例胰腺癌病例。在不同的年龄组中，我们在前瞻性队列中研究了吸烟、肥胖、糖尿病、身高和非 O 血型；在 GWAS 中研究了 22 个先前确定的单核苷酸多态性的加权多基因风险评分；以及在 SEER 计划中研究了男性性别和黑人种族。
在前瞻性队列中，所有五个风险因素与年轻参与者的胰腺癌风险相关性更强，而在年龄>70 岁的参与者中，相关性减弱。与无风险因素的参与者相比，有 3 至 5 个风险因素的参与者的风险比分别为≤60 岁年龄组的 9.24（95%置信区间[CI] 4.11-20.77）、61-70 岁年龄组的 3.00（95%CI 1.85-4.86）和>70 岁年龄组的 1.46（95%CI 1.10-1.94）（P=3×10）。这些因素共同导致了这些年龄组中分别有 65.6%、49.7%和 17.2%的胰腺癌发病。在 GWAS 和 SEER 计划中，多基因风险评分、男性性别和黑人种族与胰腺癌的关联在年轻个体中均更强（P≤0.01）。
既定的风险因素与早发性胰腺癌的相关性更强，这强调了针对这种高度致命性恶性肿瘤的癌症预防和控制计划应根据发病年龄来启动的重要性。
