Yeo Theresa P, Hruban Ralph H, Brody Jonathan, Brune Kieran, Fitzgerald Sheila, Yeo Charles J
Thomas Jefferson University School of Nursing, Edison Building, 130 S. 9th Street, Suite 1252, Philadelphia, PA 19107, USA.
J Gastrointest Surg. 2009 Aug;13(8):1487-94. doi: 10.1007/s11605-009-0923-6. Epub 2009 May 21.
Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. This study characterizes one of the largest national registries of familial PC (FPC) and sporadic PC (SPC), focusing on demographics, clinical factors, self-reported environmental and occupational lifetime exposures, and survival status.
Reported risk factors for PC include advancing age, a family history of PC, high-risk inherited syndromes, cigarette, cigar, and pipe smoking, exposure to occupational and environmental carcinogens, African-American race, high fat/high cholesterol diet, obesity, chronic pancreatitis, and diabetes mellitus.
This retrospective cross-sectional, case-only analysis includes cases of FPC (n = 569) and SPC (n = 689) from the Johns Hopkins National Familial Pancreas Tumor Registry (NFPTR) enrolled between 1994 and 2005.
FPC smokers with environmental tobacco smoke (ETS) exposure were diagnosed at a significantly younger mean age (63.7 years) as compared to FPC non-smokers without ETS exposure (66.6 years; p = 0.05). Non-smoker ETS-exposed cases were diagnosed with PC at a significantly younger mean age (64.0 years) compared to non-smoker non-ETS-exposed cases (66.5 years) (p < 0.0004). The mean age at diagnosis for Ashkenazi Jewish SPC subjects was significantly younger (by 2.1 years) than Ashkenazi Jewish FPC cases (p = 0.05). In addition, Ashkenazi Jewish FPC subjects who smoked were diagnosed 5.9 years earlier than Ashkenazi Jewish FPC non-smokers (p = 0.05). The median length of survival for unresected FPC cases was significantly shorter (168 days) as compared to unresected SPC cases (200 days) (p = 0.04). Survival was improved in resected cases, 713 days for FPC cases and 727 days for SPC cases, but was not significantly different between the groups (p = 0.4). Mild to moderate multiplicative interaction was found between a family history of PC and exposure to asbestos, environmental radon, and environmental tobacco smoke (ETS), as evidenced by odds ratios >1.0.
These are the first data to show that occupational and environmental exposures may act synergistically with inherited or acquired genetic polymorphisms, resulting in earlier occurrence of PC. Exposure to cigarette smoking and ETS exposure in non-smokers when younger than 21 years of age are associated with a younger mean age of diagnosis in FPC and SPC cases and Ashkenazi Jewish smokers, when compared to non-exposed cases. Risk prediction models which take into account environmental exposures as well as family history may more accurately predict the risk of PC. High-risk individuals will likely benefit from early identification of pre-malignant lesions and molecular profiling, as methods of early detection, prevention, and personalized therapy.
胰腺癌（PC）是美国癌症死亡的第四大主要原因。本研究对最大的家族性胰腺癌（FPC）和散发性胰腺癌（SPC）国家登记库之一进行了特征描述，重点关注人口统计学、临床因素、自我报告的一生环境和职业暴露以及生存状况。
报道的胰腺癌风险因素包括年龄增长、胰腺癌家族史、高风险遗传综合征、吸烟（香烟、雪茄和烟斗）、接触职业和环境致癌物、非裔美国人种族、高脂肪/高胆固醇饮食、肥胖、慢性胰腺炎和糖尿病。
这项回顾性横断面、仅病例分析包括1994年至2005年间登记在约翰霍普金斯国家家族性胰腺肿瘤登记库（NFPTR）中的FPC病例（n = 569）和SPC病例（n = 689）。
与无环境烟草烟雾（ETS）暴露的FPC非吸烟者相比，有ETS暴露的FPC吸烟者诊断时的平均年龄显著更年轻（63.7岁）（66.6岁；p = 0.05）。与无ETS暴露的非吸烟病例相比，有ETS暴露的非吸烟病例诊断为胰腺癌时的平均年龄显著更年轻（64.0岁）（66.5岁）（p < 0.0004）。德系犹太SPC受试者的诊断平均年龄比德系犹太FPC病例显著更年轻（年轻2.1岁）（p = 0.05）。此外，吸烟的德系犹太FPC受试者比不吸烟的德系犹太FPC受试者诊断时间早5.9年（p = 0.05）。与未切除的SPC病例（200天）相比，未切除的FPC病例的中位生存时间显著更短（168天）（p = 0.04）。切除病例的生存情况有所改善，FPC病例为713天，SPC病例为727天，但两组之间无显著差异（p = 0.4）。胰腺癌家族史与接触石棉、环境氡和环境烟草烟雾（ETS）之间存在轻度至中度的相乘交互作用，优势比>1.0表明了这一点。
这些是首批数据，表明职业和环境暴露可能与遗传或获得性基因多态性协同作用，导致胰腺癌更早发生。与未暴露病例相比，21岁以下的非吸烟者吸烟和ETS暴露与FPC和SPC病例以及德系犹太吸烟者诊断时更年轻的平均年龄相关。考虑环境暴露以及家族史的风险预测模型可能更准确地预测胰腺癌风险。高危个体可能会从癌前病变的早期识别和分子分析中受益，作为早期检测、预防和个性化治疗的方法。
