Pancreatic Cancer Screening: State of the Art

Christian Gemmel; Axel Eickhoff; Lars Helmstädter; Jürgen F Riemann

Disclosures

Expert Rev Gastroenterol Hepatol. 2009;3(1):89-96. 

In This Article

Risk Factors for Pancreatic Cancer

In terms of ethnic disposition, African-Americans, Ashkenazi Jews, Pacific islanders and native New Zealanders appear to have a higher risk of pancreatic cancer then other races, which might be due to a unique combination of a wide array of environmental and inherited factors ( Table 1 ).[9,10]

Cigarette smoking is an important risk factor with regards to the development of pancreatic cancer. Smokers seem to have a dose-dependent risk, which ranges from two to five.[11,12,13,14] In patients with a family history of pancreatic cancer, smoking increases the risk of developing pancreatic cancer and they tend to develop this disease 10-20 years earlier.[11] Passive smoking does not seem to be associated with a higher risk.[15]

Diabetes mellitus has been shown to be associated with a twofold higher risk for pancreatic cancer.[16,17,18] However, the causality between diabetes and pancreatic cancer is still controversial, with evidence on both sides: diabetes mellitus predisposes a patient to pancreatic cancer; and pancreatic cancer itself has been associated with glucose intolerance and diabetes.[19,20]

Chronic pancreatitis is associated with a two- to 26-fold higher risk of developing pancreatic cancer,[21,22,23] and obesity with a twofold higher risk.[24]

Several diseases have also been shown to be associated with pancreatic cancer, underlining the importance of genetic risk factors.

Individuals with a family history of pancreatic cancer have a considerably increased risk of developing pancreatic cancer,[25] and up to 17% of all pancreatic cancers appear to be hereditary in nature.[26] Familial pancreatic cancer is defined as at least two first-degree relatives being affected with pancreatic cancer without evidence of other familial diseases. According to the National Familial Pancreatic Tumor Registry, the risk of developing pancreatic cancer in relatives of families with at least two affected first-degree relatives is 18-fold higher than that of sporadic cases. Individuals with three affected first-degree relatives have a 57-fold increased risk of developing pancreatic cancer.[27]

Germline mutations (e.g., BRCA2,[28]p16,[29]PRSS1[30] and STK11/LKB1[31]) are known to be associated with hereditary pancreatic cancer syndromes.

Hereditary breast and ovarian cancer is associated with a two- to ninefold risk.[32,33]

Mutations involving BRCA2 as a key regulator of gene transcription are associated with hereditary breast and ovarian cancer. Some of those families have a high incidence of pancreatic cancer and a two- to ninefold higher risk.[32,33] Peutz-Jeghers syndrome, as an autosomal dominant disorder with a multicancer phenotype, is associated with a 132-fold risk and a lifetime risk of 36% for ages 15-64 years.[34] The germline mutations responsible for this syndrome are found to be in the STK11/LKB1 gene. Familial adenomatous polyposis is associated with a fivefold risk,[35] and cystic fibrosis, as an autosomal recessive disease, with a two- to 61-fold risk of developing pancreatic cancer.[36,37,38]

Hereditary pancreatitis, as an autosomal dominant disorder, has also been linked with an increased lifetime risk of pancreatic cancer. It is associated with a 54-fold risk and an estimated lifetime risk of pancreatic cancer of 70 years of age.[30,39] In 60% of cases, the PRSS1 mutation appears to be involved and leads to a high incidence of cancer 30-40 years after the onset of recurrent attacks of pancreatitis.

Familial atypical multiple mole melanoma (FAMMM) is an autosomal dominant, inherited syndrome characterized by multiple nevi, atypical nevi and multiple melanomas. According to studies from Bartsch and colleagues and Vasen and coworkers, a p16 mutation that is associated with FAMMM is responsible for the increased risk of pancreatic cancer among affected individuals with a lifetime risk of up to 16%.[29,40]

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