Biomarkers for Early Detection

Christopher J Hoimes1, Matthew T Moyer2, Muhammad Wasif Saif1
1Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA. 2Division of
Gastroenterology/Hepatology, Penn State Hershey Medical Center, Penn State College of
Medicine. Hershey, PA, USA
Pancreatic cancer is the second most frequent gastrointestinal malignancy with an unabated mortality that reflects the advanced stage
of presentation. Detection of early disease through screening likely is the best way to meaningfully prolong survival. The
development of biomarkers for screening holds enormous promise for increasing early detection and impacting mortality. Many
biomarkers have been studied including the serum protein carbohydrate antigen 19-9, vascular endothelial growth factor, and nuclear
factor kappa B, however, still no blood test or other fluid analysis reliably predicts patients with disease. The authors review
abstracts from the 2009 annual meeting of the American Society of Clinical Oncology, Orlando, FL, U.S.A., that report evidence for
early detection using a salivary biomarker array (#4630); a mucin epitope to PAM4 (#4613); a plasma nucleotide marker of hypoxia,
miR-210 (#4624); and a cleavage product of complement pathway component C3b, iC3b (#4626). The meeting featured pancreatic
cancer in over 100 research abstracts, of which, four are reviewed that focus on potential markers for early detection. When applied
to a population of high risk patients, biomarkers of early pancreatic cancer could provide a minimally invasive way of identifying
patients that require further evaluation using endoscopic tools. These molecular beacons may even be found to be sufficiently
sensitive, specific, and cost effective to be applied to a broader population of patients.
Pancreatic cancer is the second most frequent
gastrointestinal malignancy and has a median survival
of less than one year with over 96% incurable at the
time of diagnosis [1, 2]. In 2002, there were roughly
227,000 deaths worldwide with a mortality-to-
incidence ratio of 0.98 [3]. Many biomarkers have been
studied including the serum protein carbohydrate
antigen 19-9, vascular endothelial growth factor, and
nuclear factor kappa B, however, still no blood test or
other fluid analysis reliably predicts patients with
disease. The United States Preventative Services Task
Force (USPSTF) does not currently recommend a
screening program for average risk individuals [4],
however high risk patients with known inherited
predisposition are encouraged to enroll in screening
and surveillance clinical trials that are evaluating an
effective algorithm using endoscopic ultrasound (EUS)
or magnetic resonance imaging (MRI) [5, 6, 7, 8].
Although the etiology of the malignancy remains
unknown, our understanding of key molecular and
tumor microenvironment events can lead to biomarker
candidates for screening or surveillance.
For patients with pancreatic cancer, surgery is the only
durable treatment but less than 20% of tumors are
resectable at the time of diagnosis. Therefore,
prognosis is improved with early diagnosis and can
even be cured with resection of lesions that are less
than one centimeter and without evidence of
lymphovascular invasion [9]. A successful screening
strategy should be attainable given the advancement in
our knowledge of premalignant stages of the disease
such as intraductal papillary mucinous neoplasms
(IPMN) and pancreatic intraepithelial neoplasia
(PanIN), advanced endoscopy techniques, and
improvements in retroperitoneal-space imaging.
Indeed, the disease usually rapidly progresses and
given the penchant to metastasize very early in its
course, assessment intervals need to be sufficiently
frequent and the economic feasibility and increased
complication risk needs to be brought into balance.
A biomarker that is both sensitive and specific to
pancreatic neoplasia - including even IPMN or PanIN -
would complement EUS and MRI modalities and if
Keywords Adenocarcinoma; Antibodies, Monoclonal; CA-19-9
Antigen; Carcinoma, Pancreatic Ductal; Complement C3b; Early
Detection of Cancer; Endoscopes; MicroRNAs; Mucins;
Pancreatic Neoplasms
Abbreviations USPSTF: United States Preventative Services Task
Correspondence Muhammad Wasif Saif
Yale Cancer Center, Yale University School of Medicine, 333
Cedar Street, FMP 116, New Haven, CT, USA
Phone: +1-203.737.1569Fax: +1-203.785.3788
Document URL

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JOP. Journal of the Pancreas - - Vol. 10, No. 4 - July 2009. [ISSN 1590-8577]
adequately safe, sensitive, and economically feasible
could then be applied to a lower risk population.
Screening could make a tremendous impact on this
disease as pancreatic cancer is prevalent with a high
morbidity and mortality, and resection at an early stage
does increase overall survival. We review some of the
newest developments in biomarker identification
presented at the 2009 annual meeting of the American
Society of Clinical Oncology (ASCO) including
evidence for early detection using a salivary biomarker
array (#4630); a mucin epitope to PAM4 (#4613); a
plasma nucleotide marker of hypoxia, miR-210
(#4624); and a cleavage product of complement
pathway component C3b, iC3b (#4626) (Table 1).
Review of Abstracts
1. PAM4
PAM4 is a purified monoclonal antibody that was
generated against mucin collected from the tumor of a
RIP1 xenograft and was shown in previous studies to
be a marker of early pancreatic adenocarcinoma with
better expression in more well differentiated versus less
differentiated pancreatic adenocarcinomas [11, 17].
The group presented the results of additional in vitro
immunohistochemistry, and ex vivo
immunoassay (EIA) studies at the 2009 ASCO meeting
[10]. The immunohistochemistry staining patterns with
PAM4 gave a strong labeling in 92% of the mucinous
cystic neoplasm samples, indicating a good affinity for
this lesion. They also report that they were able to
determine correlation with staining to pathologic grade
of lesion. They previously reported on their EIA
methodology to differentiate pancreatic cancer from
pancreatitis with a sensitivity of 77% and specificity of
95% [18]. Here they carry that further and apply their
EIA technique to a set of samples with known
pancreatic staging (n=49; 25% stage I) and controls
(n=13). The investigators were able to show an overall
specificity of 82% and sensitivity of 85% calculated by
ROC curve analysis. One should note that the study
was limited by a small sample size and a particularly
small number of patients (n=12) with stage I disease.
As their previous pre-clinical work showed a difference
in labeling affinity for degree of differentiation, it
would be worthwhile to see correlations with histologic
2. miR-210
MicroRNAs (miRs) are a class of small noncoding
RNAs that regulate vast numbers of transcripts at the
posttranscriptional level [19] and are emerging as
important modulators of angiogenesis [20]. Specific
endothelial miRs have been implicated in controlling
cellular responses to angiogenic stimuli, including
miR-210 which has been found to be pro-
vasculogenic/angiogenic [14, 21]. Hypoxia causes
increased expression of miR-210 via hypoxia inducible
factor which increases vasculogenesis [14] likely by
interacting with ephrin-A3 (the interaction of miR-210
on the milieu of ephrins, either inhibitory or
stimulatory, has not been fully elucidated). Ho et al.
hypothesized that miR-210 would be overexpressed in
pancreatic cancer which is known to be a hypoxic
environment. The group measured miR-210 in plasma
from a cohort of 11 patients with known pancreatic
cancer and compared to healthy controls. In the
subsequent validation cohort of 12 patients, they
measured a statistically significant 4-fold increase in
miR-210 levels in pancreatic cancer patients. This
hypothesis driven study shows promise in their early
results, and larger cohorts would be helpful in further
characterizing this relationship. This is a non-specific
marker of hypoxia (presumably will be found in other
cases of rapid tissue growth, acute or chronic ischemia,
and other tumors) and would be informative to
characterize the miR-210 profile with histologic grade,
at diagnosis, and understand variations during
treatment that may correlate with disease.
Table 1. Summary of reviewed abstracts.
Abstract #
#4613 [10]
Gold D, et al.
Monoclonal antibody:
• PAM4 is an IgG1 antibody originally generated against mucin from a RIP1 murine pancreatic cancer
xenograft [11].
• PAM4 identifies a “unique antigen” in precursor and neoplasia lesions.
• Abstract does not specify the cancer cell's epitope or target; unclear if it has been characterized.
#4624 [12]
Ho AS, et al
• miR-210 is an endothelial localized pro-angiogenic microRNA.
• miR-210 responds to hypoxia inducible factor and inhibits endothelial ligand ephrin A3 [13, 14].
• miR-210 is elevated in hypoxic cancers such as pancreatic, and non- specific and likely not a marker
of precursor/early lesions.
#4626 [15]
Marten A, et al.
Soluble iC3b
• iC3b is the inactivated complement component that is expressed on apoptotic cells, including
pancreatic cancer cells.
• iC3b binds with CR3 and acts as an opsonin and required for phagocytosis of apoptotic cells by
macrophages or dendritic cells.
• iC3b was elevated prior to radiographic evidence of tumor, and combining with CA 19-9 values
increased sensitivity and specificity.
#4630 [16]
Wong DT, et al.
Multiplex of mRNA of
and microbial S. mitis
• Used a human genome array to identify mRNA or bacterial signatures in saliva of patients with
pancreatic cancer.
• A combination of 4 mRNA markers and one bacterial biomarker gave the best sensitivity and
specificity in identifying pancreatic cancer patients.
CA 19-9: carbohydrate antigen 19-9; iC3b: inactivated C3b; miR: microRNA

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3. Soluble iC3b
The alternative complement pathway requires C3 and
C3b for activation, and control of C3b amplification is
tightly regulated by cleavage to an inactive form, iC3b.
Thus, iC3b is the inactivated complement component
that is expressed on apoptotic cells, including
pancreatic cancer cells, which may be necrotic from
treatment or hypoxic conditions. iC3b binds with CR3
and acts as an opsonin and required for phagocytosis of
apoptotic cells by macrophages or dendritic cells.
Marten et al. analyzed soluble iC3b in 232 plasma
samples taken from subjects post pancreatic cancer
resection, healthy volunteers, and high risk patients
[15]. This prospective study followed patients with
paired serum analysis and imaging every three months
and reported that up to four months prior to
radiographic defined recurrence, soluble iC3b plasma
levels were significantly increased resulting in an AUC
of 0.85 which could be further increased by combining
it with the tumor marker CA 19-9 (AUC=0.92).
Expression of soluble iC3b is non-specific which the
investigators recognize that therefore combined their
information with CA 19-9 levels. Despite its non-
specific nature, expression of iC3b is especially
important in understanding the interaction of a patient’s
immune system and tumor, as iC3b levels could reflect
ability for immune tolerance to the tumor via
presentation to dendritic cells [22]. This component
warrants additional investigation in all clinical states
including at diagnosis, during treatment, and with
4. Salivary Multiplex of mRNA and Bacterial
Investigators evaluated the transcriptome of patients’
saliva for differences between pancreatic cancer,
pancreatitis, and healthy controls. They started with 11
candidate mRNAs and two microbial biomarkers and
applied a logistic regression model using a combination
of three of the mRNA biomarkers (ACRV1, DMXL2,
and DPM1) and found a 93% sensitivity and 90%
specificity for pancreatic cancer from healthy controls.
Further analysis found that when they combined four
biomarkers (mRNA biomarkers ACRV1, DMXL2,
DPM1, and bacterial biomarker S. mitis) they could
differentiate pancreatic cancer patients from all non-
cancer patients (chronic pancreatitis and healthy
controls) with 93% sensitivity and 85% specificity
[16]. While the study is limited by a small sample size,
it does demonstrate a novel and potentially important
multiplex salivary biomarker panel for the non-
invasive detection of pancreatic cancer.
Pancreatic cancer meets criteria of the USPSTF and
WHO for consideration of screening given its
prevalence, coupled with its considerable mortality and
potential for durable and meaningful disease free
period when caught early and resected. The pancreas is
different from other tubular parts of the gastrointestinal
tract in that the retroperitoneal space is more difficult
to access, sample, and image. This makes anatomy-
driven modes of screening and surveillance such as
endoscopy or cross-sectional imaging dependent upon
availability of an experienced and technically adept
physician, and widespread screening with these
modalities would be cost prohibitive. Therefore,
patients with high risk for disease are targeted and
clinical trials have shown EUS as promising for
screening and surveillance for this population [7, 23].
As screening trials for the high risk populations are
ongoing with a primary focus on imaging or
endoscopy, preclinical efforts are focused on
identifying new biomarkers. Candidate biomarkers can
be hormones, enzymes, oncofetal antigens, proteins or
nucleotides that are either overexpressed in malignant
or premalignant lesions or found to be unique and not
in normal tissue. The 2009 ASCO annual meeting
presented the data of Gold et al. [10] who reported an
antigenic determinant that appears to be unique to
cancer cells as expressed by the PAM4 paratope and
could be useful in early detection. This yet undefined
epitope deserves identification and classification.
Marten et al. [15] and Ho et al. [12] discuss results
where they saw overexpression of a complement
pathway component and a pro-angiogenic nucleotide,
respectively, that reach statistical significance when
compared to patients without cancer, and soluble iC3b
became elevated 4 months prior to radiographic
progression. Wong et al. [16] used a multiplex model
of 4 mRNAs and a bacterial biomarker that is detected
in saliva and able to differentiate patients with
pancreatic cancer from those with other pancreas
disease or healthy controls. While these are
encouraging findings, larger cohorts are needed to
better gauge their sensitivity and specificity, and to
understand their profile amongst the range of
presentation of disease - from premalignant to poorly
differentiated lesions. Furthermore, it is possible a
combination of markers, as done by Marten et al. and
Wong et al. and even modalities with imaging or EUS,
will be needed to achieve sufficient reliability.
Discussion of candidate modalities must consider the
population to target. The cause of most pancreatic
cancer cases remains unknown, though several risk
factors have been identified. Smoking is the most
extensively studied risk factor for pancreatic cancer
and was first identified in the 1960s while studying its
link to lung cancer [24]. Smokers carry at least a 2-fold
increased risk with a cigarette-dose-response, and 25%
of all pancreatic cancer is caused by this single factor
[1, 25]. Other factors that portend a high risk include
advancing age, a family history of pancreatic cancer,
hereditary pancreatitis, and germline cancer syndromes
including Peutz-Jeghers syndrome, familial atypical
multiple mole melanoma syndrome, familial breast
cancer, and others (Table 2). In addition, male gender
and African American race are associated with a slight
increased risk. Heavy alcohol consumption may

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JOP. Journal of the Pancreas - - Vol. 10, No. 4 - July 2009. [ISSN 1590-8577]
increase risk in some patients insofar as it increases
risk for chronic pancreatitis, though the association
between alcohol and pancreatic cancer has not been
proven in multiple trials. Diabetes mellitus may be
associated with pancreatic cancer, though it is hard to
distinguish a cause versus effect role.
EUS and MRI can be complimentary techniques for the
detection of lesions in individuals at high risk for
developing pancreatic cancer and the addition of
biomarkers to EUS and MRI modalities could further
increase sensitivity and specificity. Results of two
prospective trials evaluating EUS and MRI for high
risk patients were recently presented at the 2009
Digestive Disease Week, Chicago, IL, USA. Harinck et
al. evaluated high risk individuals (n=33) annually
using EUS, MRI, and both, with investigators blinded
to the alternative imaging modality [32]. Eight (24%)
patients had focal lesions; detected by both EUS and
MRI in 4 (12%), by MRI alone in 2 (6%), and by EUS
alone in 2 (6%). The lesions missed by EUS were two
simple cysts, and the MRI missed one cyst and one
Screening for pancreatic cancer in patients at high risk
often identifies neoplasms that can be resected upon
the first screen. Verna et al. reported a prospective
MRI and EUS screening of individuals with high risk
for pancreatic cancer due to family history, a hereditary
cancer syndrome, or familial pancreatic cancer [33].
Fifty-one patients (average age: 52 years) in 43
families completed initial testing over three years, and
nine (18%) of the 51 patients had malignant or pre-
malignant lesions identified in the initial round of
testing that were successfully resected.
Detection and resection of early disease currently is the
only treatment which can offer a long durable control
or even cure. Shifting the preponderance of advanced
stage at diagnosis to premalignant or T1 lesions
through screening selected populations holds enormous
promise for a favorable impact on mortality. Improved
early detection screening modalities are needed and
molecular beacons may even be found to be
sufficiently sensitive, specific, and cost effective to be
applied to a broader population of patients. Synergies
are anticipated where reliable biomarker discoveries
translate into a new imaging agent or therapeutic target.
Conflict of interest The authors have no potential
conflicts of interest
1. American Cancer Society (ACS). Cancer Facts & Figures 2009
Atlanta, GA, USA: American Cancer Society (ACS), Editor. 2009:
2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer
statistics, 2009. CA Cancer J Clin 2009 June 9. [PMID 19474385]
Table 2. Risk factors for pancreatic adenocarcinoma to consider when determining populations to screen. (adapted from Rulyak [31] and Larghi et
al. [23]).
Risk classes
or gene
High risk (RR ≥ 5%)
- Family history of pancreatic cancer (Seattle cohort)
- Family history of pancreatic cancer (US National Tumor Reg):
- Pancreatic cancer in ≥ 3 first degree relatives
- Pancreatic cancer in 2 first degree relatives
- Familial multiorgan cancer syndromes:
- Peutz-Jeghers syndrome
- Familial atypical multiple mole melanoma (FAMMM)
- Hereditary breast-ovarian cancer
- Familial adenomatous polyposis
- Familial breast cancer
- Hereditary pancreatitis
- Cystic fibrosis
Smokers develop early onset pancreas cancer [26]
Five5 to 10 fold risk for first-degree relatives [27]
RR = 32
RR = 6.4
RR = 132
Cumulative lifetime risk = 17
RR = 5
RR = 5
RR =53
RR = 32
Moderate risk
- Male gender
- African American race
- Tobacco
- Chronic pancreatitis
- Hereditary breast-ovarian cancer
- Pancreatic cancer in one first degree relative
- Germline diseases associated with pancreatic cancer:
- Hereditary nonpolyposis colorectal cancer (HNPCC)
- Li-Fraumeni
- Ataxia-telengiectasia
- Fanconi’s anemia
3p, 9p, 9q,16q
RR = about 3 [25]
RR = 4.5
Breast cancer is most common tumor [29]
Average risk (RR ≤ 1.5%)
- Moderate alcohol use
- Coffee consumption
RR: relative risk

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JOP. J Pancreas (Online) 2009 Jul 6; 10(4):352-356.
JOP. Journal of the Pancreas - - Vol. 10, No. 4 - July 2009. [ISSN 1590-8577]
3. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,
2002. CA Cancer J Clin 2005; 55:74-108. [PMID 15761078]
4. Agency for Healthcare Research and Quality (AHRQ).
Screening for Pancreatic Cancer. Recommendation Statement. U.S.
Department of Health & Human Services. Washington, DC, USA,
5. Brentnall TA, Bronner MP, Byrd DR, Haggitt RC, Kimmey MB.
Early diagnosis and treatment of pancreatic dysplasia in patients with
a family history of pancreatic cancer. Ann Intern Med 1999;
131:247-55. [PMID 10454945]
6. Canto MI, Goggins M, Yeo CJ, Griffin C, Axilbund JE, Brune
K, et al. Screening for pancreatic neoplasia in high-risk individuals:
an EUS-based approach. Clin Gastroenterol Hepatol 2004; 2:606-21.
[PMID 15224285]
7. Canto MI. Screening for pancreatic neoplasia in high-risk
individuals: who, what, when, how? Clin Gastroenterol Hepatol
2005; 3(7 Suppl. 1):S46-8. [PMID 16012996]
8. Brand RE, Lerch MM, Rubinstein WS, Neoptolemos JP,
Whitcomb DC, Hruban RH, et al. Advances in counselling and
surveillance of patients at risk for pancreatic cancer. Gut, 2007.
56(10): p. 1460-1469. [PMID 1787257]
9. Ariyama J, Suyama M, Satoh K, Sai J. Imaging of small
pancreatic ductal adenocarcinoma. Pancreas 1998; 16:396-401.
[PMID 9548685]
10. Gold D, Modrak DE, Newsome G, Karanjawala Z, Hruban R,
Goggins M, Goldenberg DM. Detection of early-stage pancreatic
carcinoma. J Clin Oncol 2009; 27(15 Suppl.):Abstract 4613.
11. Gold DV, Lew K, Maliniak R, Hernandez M, Cardillo T.
Characterization of monoclonal antibody PAM4 reactive with a
pancreatic cancer mucin. Int J Cancer 1994; 57:204-10. [PMID
12. Ho AS, Huang X, Cao H, Koong AC, Le QT. Detection of
circulating hypoxia-regulated miR-210 in pancreatic adenocarcinoma
patients. J Clin Oncol 2009; 27(15 Suppl.):Abstract 4624.
13. Pulkkinen K, Malm T, Turunen M, Koistinaho J, Ylä-Herttuala
S. Hypoxia induces microRNA miR-210 in vitro and in vivo ephrin-
A3 and neuronal pentraxin 1 are potentially regulated by miR-210.
FEBS Lett 2008; 582:2397-401. [PMID 18539147]
14. Fasanaro P, D'Alessandra Y, Di Stefano V, Melchionna R,
Romani S, Pompilio G, et al. MicroRNA-210 modulates endothelial
cell response to hypoxia and inhibits the receptor tyrosine kinase
ligand Ephrin-A3. J Biol Chem 2008; 283:15878-83. [PMID
15. Marten A, Büchler MW, Wente MN, Schmidt J. Soluble iC3b as
an early marker for pancreatic adenocarcinoma compared to CA 19.9
and radiology. J Clin Oncol 2009; 27(15 Suppl.):Abstract 4626.
16. Wong DT, Zhang L, Farrell J, Zhou H, Elashoff D, Gao K,
Paster B. Salivary biomarkers for pancreatic cancer detection. J Clin
Oncol 2009; 27(15 Suppl.):Abstract 4630.
17. Gold DV, Karanjawala Z, Modrak DE, Goldenberg DM, Hruban
RH. PAM4-reactive MUC1 is a biomarker for early pancreatic
adenocarcinoma. Clin Cancer Res 2007; 13:7380-7. [PMID
18. Gold DV, Modrak DE, Ying Z, Cardillo TM, Sharkey RM,
Goldenberg DM. New MUC1 serum immunoassay differentiates
pancreatic cancer from pancreatitis. J Clin Oncol 2006; 24:252-8.
[PMID 16344318]
19. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of
post-transcriptional regulation by microRNAs: are the answers in
sight? Nat Rev Genet 2008; 9:102-14. [PMID 18197166]
20. Suárez Y, Sessa WC. MicroRNAs as novel regulators of
angiogenesis. Circ Res 2009; 104:442-54. [PMID 19246688]
21. Crosby ME, Kulshreshtha R, Ivan M, Glazer PM. MicroRNA
regulation of DNA repair gene expression in hypoxic stress. Cancer
Res 2009; 69:1221-9. [PMID 19141645]
22. Schmidt J, Klempp C, Büchler MW, Märten A. Release of iC3b
from apoptotic tumor cells induces tolerance by binding to immature
dendritic cells in vitro and in vivo. Cancer Immunol Immunother
2006; 55:31-8. [PMID 15891882]
23. Larghi A, Verna EC, Lecca PG, Costamagna G. Screening for
pancreatic cancer in high-risk individuals: a call for endoscopic
ultrasound. Clin Cancer Res 2009; 15:1907-14. [PMID 19276278]
24. Wynder EL, Mabuchi K, Maruchi N, Fortner JG. Epidemiology
of cancer of the pancreas. J Natl Cancer Inst 1973; 50:645-67.
[PMID 4350660]
25. Lin Y, Tamakoshi A, Kawamura T, Inaba Y, Kikuchi S,
Motohashi Y, et al. A prospective cohort study of cigarette smoking
and pancreatic cancer in Japan. Cancer Causes Control 2002; 13:249-
54. [PMID 12020106]
26. Rulyak SJ, Lowenfels AB, Maisonneuve P, Brentnall TA. Risk
factors for the development of pancreatic cancer in familial
pancreatic cancer kindreds. Gastroenterology 2003; 124:1292-9.
[PMID 12730869]
27. Klein AP, Brune KA, Petersen GM, Goggins M, Tersmette AC,
Offerhaus GJ, et al. Prospective risk of pancreatic cancer in familial
pancreatic cancer kindreds. Cancer Res 2004; 64:2634-8. [PMID
28. Watson P, Lynch HT. Extracolonic cancer in hereditary
nonpolyposis colorectal cancer. Cancer 1993; 71:677-85. [PMID
29. Ghadirian P, Lynch HT, Krewski D. Epidemiology of pancreatic
cancer: an overview. Cancer Detect Prev 2003; 27:87-93. [PMID
30. van der Heijden MS, Yeo CJ, Hruban RH, Kern SE. Fanconi
anemia gene mutations in young-onset pancreatic cancer. Cancer Res
2003; 63:2585-8. [PMID 12750283]
31. Rulyak SJ. Identification and management of familial pancreatic
cancer. In: Kochman ML, ed. Gastrointestinal Oncology. Thorofare,
NJ, USA: Slack Inc., 2005:68-71.
32. Harinck F, Kluijt I, Poley JW, Cats A, Aalfs CM, Gouma DJ, et
al. Comparative yield of endosonography and magnetic resonance
imaging in individuals at high-risk for pancreatic cancer.
Gastroenterology 2009; 136(5 Suppl. 1):A147 (Abstract 965).
33. Verna EC, Sy C, Stevens PD, Stavropoulos SN, Hwang C,
Chabot JA, Frucht H. Pancreatic cancer screening in a prospective
cohort of high risk patients: an effective and comprehensive strategy
of genetics and imaging. Gastroenterology 2009; 136(5 Suppl.
1):A451 (Abstract M194

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