N U TR IT ION RE S EA R CH 5 2 ( 20 1 8 ) 1 –1 3

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Review Article

Pancreatic cancer: A critical review of dietary risk

Asmaa A. Salem, Gerardo G. Mackenzie⁎

Department of Nutrition, University of California, Davis, One Shields Ave, Davis, CA, 95616

ARTI CLE I NFO A BS TRACT

Article history: Pancreatic cancer is a deadly disease. It is estimated that about 90% of pancreatic cancer
Received 5 August 2017 cases are due to environmental risk factors. Among these, approximately 50% of pancreatic
Revised 31 October 2017 cancer cases may be attributed to diet, which is largely modifiable. Given this large
Accepted 8 December 2017 attribution to diet, there have been numerous epidemiological studies assessing the risk of
various dietary factors on the incidence of pancreatic cancer. However, many of these
Keywords: studies present conflicting and/or inconclusive findings. The objective of this review is two-
Diet fold: (a) to summarize the current evidence on the association between various dietary
Nutrients factors and the risk of developing pancreatic cancer and (b) to discuss what additional
Foods studies are needed to better elucidate the role of diet as a potential risk factor for pancreatic
Pancreatic cancer cancer. We summarized the evidence by using data primarily from meta-analyses and pooled
Pancreatic cancer risk analysis when available, focusing on the most studied nutrients, foods, and dietary patterns.
We observed that, while the association between individual nutrients and pancreatic cancer
risk have been heavily studied, the evidence is mostly conflicting and inconclusive. In
contrast, the evidence of certain associations among dietary patterns and pancreatic cancer
risk is clearer, has more power, and is less conflicting. Therefore, we propose a shift in the
focus of nutritional epidemiological research with regards to pancreatic cancer risk. We
discourage further epidemiological research studies that focus on single nutrients, whereas
we strongly encourage additional studies that investigate how a combination of diet and
other lifestyle factors may promote or prevent pancreatic carcinogenesis.
© 2017 Elsevier Inc. All rights reserved.

Article Outline

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
3. Findings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
3.1. Nutrients and pancreatic cancer risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
3.1.1. Vitamin C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3.1.2. Folate (vitamin B9) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3.1.3. Vitamin E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
3.1.4. Retinoids and carotenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Abbreviations: HCAs, Heterocyclic amines; AGE, Advanced glycation end products; NOCs, N-nitroso compounds; MD, Mediterranean diet.
⁎ Corresponding author at: Department of Nutrition, University of California, Davis, One Shields Ave., Davis, CA, 95616. Tel.: +1 530 752
2140; fax: +1 530 752 8966.
E-mail address: ggmackenzie@ucdavis.edu (G.G. Mackenzie).

https://doi.org/10.1016/j.nutres.2017.12.001
0271-5317/© 2017 Elsevier Inc. All rights reserved.
2 N U TR IT ION RE S EA R CH 52 ( 20 1 8 ) 1 –1 3

3.1.5. Vitamin D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3.1.6. Selenium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3.1.7. Lipids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3.1.8. Discussion: nutrients and pancreatic cancer risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.2. Foods and pancreatic cancer risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.2.1. Red and processed meat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.2.2. Dairy products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.2.3. Fruits and vegetables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.2.4. Whole grains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.2.5. High glycemic foods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.2.6. Alcoholic beverages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.2.7. Discussion: foods and pancreatic cancer risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.3. Dietary patterns and pancreatic cancer risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.3.1. Western-style dietary pattern. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.3.2. Prudent or healthy dietary pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.3.3. Healthy Eating Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.3.4. Mediterranean Diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3.3.5. Discussion: dietary patterns and pancreatic cancer risk . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
5. Knowledge gaps and future research directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

1. Introduction to summarize the current evidence on the association

between various dietary factors and the risk of developing
pancreatic cancer and (b) to discuss what additional studies
Pancreatic cancer, currently the fourth leading cause of
are needed to better elucidate the role of diet as a potential
cancer death worldwide [1], is projected to become the 2nd
risk factor for pancreatic cancer. Moreover, we point out some
by 2030 [2]. With a 5-year survival rate of approximately 8% [1]
of the challenges and limitations of the research and
and an average survival time of 6 months for those with
emphasize the need for future research to include well-
advanced metastasized disease [3], pancreatic cancer is one of
designed and carefully carried out clinical trials on dietary
the most fatal malignancies with an extremely dismal
patterns to better guide us to elucidate how diet may
prognosis. This exceedingly short survival time, however, is
influence the incidence of pancreatic cancer.
counterbalanced with what research shows to be a very slow
evolution lasting up to 18 years from the time of initiating
mutations in pre-cancerous lesions to metastatic disease [4].
2. Approach
This dichotomy between a slow progression and rapid fatality
strongly suggests that prevention should be a key emphasis in
Using PubMed, we searched for meta-analyses or pooled
reducing pancreatic cancer burden.
analyses of epidemiological studies assessing the association
Like many cancers, pancreatic cancer is considered to have a
between nutrients, diets, or dietary patterns and pancreatic
large environmental attributable risk [5]. It is estimated that
cancer between 2010 and August 2017. When a large cohort
only 5% to 10% of pancreatic cancer cases are hereditary, and
study conducted after a meta-analysis was found, this was
the remaining 90% to 95% are due to environmental risk factors,
referenced as well. Search parameters used were “nutrients”
which are largely modifiable [6]. Of those risk factors, smoking,
or “vitamin” or “vitamin C” or “vitamin D” or “vitamin E” or
alcohol, obesity, diet, and physical inactivity have been the
“selenium” or “folate” or “cholesterol” or “fat” or “vitamin A”
most studied, and numerous studies have shown them to be
or “diet” or “dietary pattern” or “red meat” or “fruits and
associated with increased risk. Of these, smoking and obesity
vegetables” or “whole grains” or “high glycemic” or “dairy” or
are the most well established to have a causal relationship, with
“Mediterranean diet” or “alcohol” and “pancreatic cancer.”
estimates that these factors are significant triggers in approx-
imately 33% and 16% percent of pancreatic cancer cases,
respectively [7]. However, diet may have the largest attribution
of cases; some have estimated that approximately 50% of 3. Findings
pancreatic cancer cases may be attributed to diet [8,9].
Given this large attribution to diet, there have been 3.1. Nutrients and pancreatic cancer risk
numerous epidemiological studies assessing the risk of
various dietary factors on the incidence of pancreatic cancer. Multiple micro and macro nutrients have been assessed
However, many of these studies showed conflicting and/or epidemiologically for their association with the incidence of
inconclusive findings. The objective of this review is 2-fold: (a) pancreatic cancer (Table 1). Among the vitamins, those with a
 N U TR IT ION RE S EA R CH 5 2 ( 20 1 8 ) 1 –1 3
significant and robust amount of data are the water-soluble
vitamins C and B9 and the fat-soluble vitamins D, E, and A
(along with the carotenoids). Among the minerals, selenium
has been researched more extensively. With respect to the
macronutrients, fat, including select fatty acids (eg, polyun-
saturated fatty acids) and cholesterol, have garnered much
research interest. In the sections below, we summarize the
most relevant findings for each of these selected nutrients
and discuss the limitations of the evidence.
3.1.1. Vitamin C
Vitamin C is known for its antioxidant, immune boosting
properties [10]. Given that inflammation and oxidative stress
may play a role in pancreatic carcinogenesis [11,12], it is
biologically plausible that vitamin C may mitigate this
process. In addition, vitamin C can induce apoptosis and
inhibit neoplastic lesions in the pancreas [13,14].
With regards to human epidemiological data, three recent
meta-analyses (2015-2016) have been conducted, with some
but not complete overlap in the studies included [15-17].
Ranging from 15 to 20 studies, including both case-control
and cohort designs, the pooled results of these meta-analyses
consistently show a significantly reduced risk of pancreatic
cancer for those with the highest dietary intake of vitamin C
compared to those with the lowest. The combined relative
risk in these meta-analyses ranges from 0.66 to 0.70. When
stratifying results by study design, however, this significant
inverse association remains only for case-control studies, but
does not persist in cohort studies.
Table 1 – Associations between nutrients and pancreatic cancer risk
Nutrient Potential link to pancreatic cancer
Vitamin C Boosts immune function
Antioxidant
Prevents DNA damage [10]
Folate Methyl donor
Prevent DNA double strand breaks [20]
Deficiency may lead to aberrant
methylation of tumor suppressor or
oncogenes [21].
Vitamin E Chain breaking antioxidant [28]
Growth inhibitory effect of pancreatic
cancer cells in vitro [29,30]
Vitamin A Vitamin A may mechanically reprogram
(Retinoids and pancreatic cancer stellate cells [36]
Carotenoids) β-carotene has pro-vitamin A capacity.
Other carotenoids have antioxidant and
anti-inflammatory properties [37].
Vitamin D Activates genes involved in cell
transformation: proliferation,
apoptosis, differentiation [41].
Modulates the immune system [42].
Selenium Component of antioxidant enzymes [52].
Lipids Chronic and excess dietary fat may
lead to pancreatic hypertrophy [55].
Saturated fat associated with
insulin resistance [57].
Higher Cholesterol increases
pro-inflammatory cytokines [59].
3
Given the limitations of assessing dietary intake and that
serum measures of vitamin C may more accurately indicate
intake, a few studies have investigated this relationship.
Interestingly, one small nested case control study in the EPIC
prospective cohort which followed participants for 11 years
found no association between pre-diagnostic levels of serum
vitamin C (measured once at the beginning of the study) and
pancreatic cancer risk [18]. On the other hand, another large
cohort study showed a statistically significant inverse rela-
tionship between serum vitamin C and pancreatic cancer risk,
despite finding no association for dietary intake as measured
through a 7-day food diary [19]. Although still premature,
these findings suggest the need to determine serum vitamin C
levels in future studies to better correlate the levels of this
vitamin to the incidence of pancreatic cancer.
3.1.2. Folate (vitamin B9)
Folate has been extensively studied for its link to cancer, due
to its function as a methyl donor and its role in the synthesis
of DNA nucleotides [20]. Thus, it is hypothesized that folate
may prevent DNA double strand breaks, whereas a folate
deficiency may lead to aberrant methylation patterns
resulting in the altered expression of tumor-suppressor or
oncogenes [21]. In contrast, it has been hypothesized that in
the case of pre-existing neoplastic lesions, folate may allow
for more frequent DNA replication and cell division, poten-
tially leading to further growth of cancerous lesions [20].
The current epidemiological evidence on folate and its
association with the incidence of pancreatic cancer has been
Association with pancreatic cancer risk Reference(s)
Significant reduced risk (remained significant only [15-17]
in case control studies after stratification)
Mixed results for serum vitamin C
Inverse association for dietary folate and total folate [22,23,26,27]
(remained significant only in case-control studies)
No association for supplemental folate
Non-significant U-shaped association for serum folate
Reduced risk (borderline significant association after [15,18,31]
stratification for cohort studies)
Non-significant inverse association for plasma vitamin E
Inverse association for Vitamin A and carotenoids in [15,18,39,40]
general (no association after stratification for cohort studies)
Possible inverse association for lycopene, β-carotene,
and β-cryptoxanthin after stratification by carotenoid type
Inverse association for the highest plasma levels of
β-carotene and zeaxanthin
No association for dietary intake or serum [43-47]
levels of 25-OH D3
Significant inverse association [15,19,53]
(only significant in case control studies)
No association for total fat, saturated fat, [60-65]
monounsaturated fat
Possible inverse association for
polyunsaturated fat, particularly DHA
Increased association for cholesterol
(only significant in case control studies)
4 N U TR IT ION RE S EA R CH 52 ( 20 1 8 ) 1 –1 3
largely inconsistent. A meta-analysis of 13 studies, including
7 case-controls and 6 cohorts, found an inverse association
between dietary folate and total folate for those in the highest
level of folate intake, but no association for supplemental
folate [22]. A potential limitation of this meta-analysis,
however, is the significant heterogeneity found between the
studies. On the other hand, a pooled analysis of 14 cohort
studies found no association for dietary, supplemental, or
total folate intake [23]. Among the 14 cohort studies pooled in
this analysis, only two found an association between folate
intake and pancreatic cancer risk. The ATB Cancer Prevention
Study conducted in smokers reported the lowest levels of
folate intake but found a reduced risk for those in the highest
quartile [24], whereas the Cancer Prevention Study Nutrition
Cohort II, as reported in this meta-analysis, found an
increased risk [25]. Additionally, The Singapore Chinese
Health Study, a prospective cohort not included in these
earlier analyses, found no association between dietary folate
intake and the risk of pancreatic cancer [26]. When analyzing
plasma folate levels, a nested case-control study in the EPIC
cohort found a U-shaped relationship between plasma folate
and pancreatic risk, with an increased, although non-
significant, risk for those in the highest and lowest quintiles
of plasma folate status [27]. Based on these mixed findings,
we cannot currently conclude with any degree of confidence
whether folate is associated with pancreatic cancer risk.
3.1.3. Vitamin E
Vitamin E, a well-known chain-breaking antioxidant, pre-
vents the oxidation of plasma membrane lipids, thereby
maintaining the integrity of the cell membrane [28]. Vitamin
E may prevent tumor growth by preventing DNA and cell
damage caused by the free radicals produced from oxidized
lipids [28]. Besides its role as an antioxidant, there is in vitro
evidence indicating that vitamin E can suppress the growth of
pancreatic cancer cells, [29] and this may be potentially
mediated by the increased expression of the p27 tumor
suppressor gene [30].
Two recent meta-analyses with significant overlap in
the studies included found a significant inverse association
between the highest levels of dietary intake of vitamin E
and pancreatic cancer risk [15,31]. After stratifying by study
design, both meta-analyses found a significant inverse
relationship persist in case-control studies, but differed in
their statistical outcome for cohort studies, even though
they included the same four cohort studies [15,31]. One
study concluded that the inverse relationship remained
significant for cohort studies: pooled RR 0.88 (0.79, 0.99)
[31]. The second meta-analysis concluded that the inverse
association was no longer significant in cohort studies:
pooled OR, 0.85; 95% CI, 0.68-1.06 [15]. This slight difference
appears to be dependent on the type of summary risk
calculated in each study.
When assessing plasma α-tocopherol levels, the afore-
mentioned nested case-control study in the EPIC cohort found
an inverse, but non-significant (P = .08), association for the
highest levels of plasma vitamin E and pancreatic cancer [18].
However, for every doubling of plasma α-tocopherol levels, a
40% reduction in pancreatic cancer risk was found after
analyzing data by a log-transformation.
Thus, the data, so far, suggest that there may be a small
inverse relationship between vitamin E and pancreatic cancer
risk. However, additional larger studies are needed to confirm
whether this inverse relationship is significant and/or wheth-
er it occurs only with individuals at the highest vitamin E
levels.
3.1.4. Retinoids and carotenoids
Vitamin A is essential for cell differentiation and growth, and
therefore this represents a plausible link through which it
may modulate carcinogenesis [32]. In vitro studies have
shown that the retinoids can induce apoptosis in pancreatic
cancer cells [33], as well as inhibit cell adhesion [34] and
migration [35]. In addition, vitamin A may also modulate the
pancreatic cancer microenvironment, by restoring mechani-
cal quiescence in pancreatic stellate cells, through a mecha-
nism involving the retinoic acid receptor beta (RAR-β) [36].
Besides the ability of some of the carotenoids to metabolize
to vitamin A, many of them have been ascribed antioxidant
and anti-inflammatory functions. For example, lycopene has
been found to inhibit pancreatic cancer cell proliferation
[37], and this may be mediated by the suppression of NF-κB
signaling [38].
A meta-analysis including 11 studies showed an inverse
association between the highest levels of dietary vitamin A
intake and pancreatic cancer risk [39]. A limitation of this
meta-analysis was that the majority of the studies in this
analysis were case-control and this inverse association did
not remain significant in the one cohort study included [39]. A
larger meta-analysis including 17 studies investigating vita-
min A, retinol, and the various carotenoids found a signifi-
cantly inverse association for the highest level of vitamin A
intake and pancreatic cancer risk, but no association for
retinol intake [40]. The significant inverse association found
for vitamin A, however, was only observed in case-control
studies after stratification by study design. Similarly, a
significant inverse association was found for the carotenoids
in general, but this also did not persist in cohort studies after
stratification [40].
After stratifying by carotenoid type, an inverse association
was only found for β-carotene (pooled OR, 0.78; 95% CI, 0.66-
0.92; P = .003) and lycopene (pooled OR, 0.84; 95% CI, 0.73-0.97;
P = .020) [40]. A previously mentioned meta-analysis found an
inverse association between highest levels of dietary
β-carotene, but this did not remain significant after stratifi-
cation in cohort studies [15]. Three studies in this
meta-analysis yielded a pooled inverse association between
β-cryptoxanthin and the risk of pancreatic cancer, and a
borderline significant inverse association for lycopene. No
association was found for the other carotenoids. When
measuring plasma levels of carotenoids and retinoids, the
EPIC nested case-control study found an inverse association
with pancreatic cancer risk for the highest plasma levels of
β-carotene and zeaxanthin [18]. No association was found
for plasma levels of β- cryptoxanthin, lycopene, lutein, or α-
carotene. In summary, the most consistent findings of the
mentioned studies point toward a potential inverse associ-
ation between β-carotene and pancreatic cancer risk, while
no definitive conclusions can be made for the other
retinoids/carotenoids.
 N U TR IT ION RE S EA R CH 5 2 ( 20 1 8 ) 1 –1 3
3.1.5. Vitamin D
The mechanisms linking vitamin D and cancer are related to
its role as a regulator of genes involved in cell transformation:
growth, differentiation, proliferation, and apoptosis [41]. For
example, Vitamin D regulates gate-keeper genes which prevent
damaged cells from proliferating and care-taker genes that
promote DNA repair. Vitamin D has been shown to interact
with cyclin D1 to inhibit cell proliferation, and has been
implicated in the modulation of the immune system [42].
Given these mechanisms for Vitamin D and therefore the
biological plausibility associated with its potentially chemo-
preventive functions, it is surprising that the epidemiological
evidence for its association with pancreatic cancer remains
highly inconsistent and conflicting. A meta-analysis of 9
studies with over 1 million participants found no association
between dietary intake of vitamin D or circulating levels of 25-
hydroxyvitamin D (25-OH D3) and the risk of pancreatic
cancer [43]. This is consistent with the fact that some pooled
analyses show an increased risk with higher dietary intake
[44] or with highest levels of plasma 25-OH D3 [45], whereas
another pooled analyses of case-control studies assessing
pre-diagnostic 25-OH D3 plasma levels [46] and two large
prospective cohort studies calculating a predicted vitamin D
status score [47] found a reduced risk of pancreatic cancer for
those with sufficient measured or predicted levels of vitamin D,
respectively. These conflicting results may be attributed to the
different methods of assessing vitamin D status used in the
various studies, as well as geographic location or ethnicity. For
instance, African Americans have a higher incidence of pancre-
atic cancer compared to Caucasian Americans [48-50].
Even though there is ongoing research on the potential
role of vitamin D and vitamin D receptor as a putative
treatment for pancreatic cancer [51], epidemiological data on
vitamin D status and pancreatic cancer risk report mixed
results, with no clear conclusion currently.
3.1.6. Selenium
It is currently still debated whether selenium can reduce the
risk of pancreatic cancer. Selenium is a mineral that functions
as an antioxidant. It reduces oxidative stress and DNA
damage, and is a component of some antioxidant enzymes
such as glutathione peroxidase [52].
Two meta-analyses, with significant overlap in the studies
included, revealed an inverse association for higher dietary
selenium intake and pancreatic cancer risk, but again, this
inverse association was only significant in case-control
studies after stratification by study design [15,53]. Two of the
large cohort studies included in these meta-analyses did
independently find significant inverse associations, for high
versus low selenium intake in the VITAL cohort study [54] and
for a summation of the three highest quartiles compared to
the lowest in the EPIC-Norfolk cohort [19]. Thus, based on
these studies, it is still too early to make any assumptions on
whether selenium can reduce the risk of pancreatic cancer.
3.1.7. Lipids
Two lipid compounds, fatty acids and cholesterol, have
received much research attention for their potential impact
on a variety of disease processes. With respect to pancreatic
cancer, chronic and excessive consumption of dietary fat may
5
lead to hypertrophy and hyperplasia in pancreatic tissue [55].
As dietary fat enters the duodenum, cholecystokinin is
released stimulating the release of lipase enzymes from the
pancreas. An excess, however, may lead to hypertrophy or
hyperplasia in the pancreas in order to keep up with the
demand for digestive enzymes [55]. This, in turn, may render
pancreatic tissue more susceptible to carcinogens. Addition-
ally, a high intake of fat may promote excess bile acid
secretion, which has been shown to stimulate the release of
COX-2, an eicosanoid producing enzyme that has been found
to be over-expressed in pancreatic tumors [56]. High intake of
saturated fat has also been associated with insulin resistance
[57], which may lead to diabetes, a condition shown to
increase the risk of pancreatic cancer [58]. Evidence for a
biological connection between cholesterol and pancreatic
carcinoma is more sparse, but some research indicates that
higher total cholesterol levels may be associated with
increased pro-inflammatory cytokines [59], and inflamma-
tion, as previously mentioned, plays a role in pancreatic
carcinogenesis [11].
Despite some possible mechanisms that may confer
biological plausibility to the association of fat intake and
pancreatic cancer, the epidemiological evidence fails to
support a strong link. One large meta-analysis of 19 studies
reported no association between total fat intake and pancre-
atic cancer risk, as well as no association for both fat from
animal sources or fat from vegetable sources [60]. Another
large meta-analyses of 20 studies that looked at the associa-
tion of various types of fatty acids with pancreatic cancer
incidence, found a non-significant positive association (RR =
1.13 (95% CI, 0.94-1.35) for saturated fatty acids, no association
for monounsaturated fatty acids, and an inverse association
for polyunsaturated fatty acids (RR = 0.87 (95% CI, 0.75-1.00)
[61]. These associations however only remain significant after
stratification in case-control studies. Given the intriguing
potential inverse association between polyunsaturated fatty
acids and pancreatic cancer, many studies have investigated
this relationship. Using fish intake as proxy for long-chain
polyunsaturated fatty acid (LC-PUFA) intake, a meta-analysis
of 19 studies found no association between increased LC-
PUFA intake and pancreatic cancer risk [62]. It is important to
note that most of these studies were conducted in Western
countries, where fish intake may be relatively limited. A large
prospective population-based cohort study conducted in
Japan after this meta-analysis found a non-significant inverse
association for the highest intake of marine omega-3 polyun-
saturated fatty acids. However, this inverse relationship was
significant (P = .03) specifically for docosahexaenoic acid
(DHA) [63]. Thus, the data currently available shows no
convincing association between fat intake and pancreatic
cancer risk, with larger more robust trials needed to conclu-
sively determine whether an inverse association between
omega-3 fatty acids and pancreatic cancer risk exists.
With respect to cholesterol, one meta-analysis found a
significantly positive association between highest dietary
cholesterol intake and pancreatic cancer risk. However, this
relationship only remained significant in case-control studies
after stratification [64]. Another meta-analysis, which includ-
ed most but not all of the studies in the previously mentioned
meta-analysis, also found a significant positive association
6 N U TR IT ION RE S EA R CH 52 ( 20 1 8 ) 1 –1 3
for dietary cholesterol intake, but again this relationship only
remained significant in case-control studies, and when
stratifying for geographic location, was only significant for
studies conducted in North America [65]. A dose–response
analysis indicated that for every 100 mg/day increase in
dietary cholesterol, there was a significant 8% increase in risk
for pancreatic cancer [65].
3.1.8. Discussion: nutrients and pancreatic cancer risk
This survey of the literature on the association between
various nutrients and pancreatic cancer risk brings up some
important points for consideration. First, it is common to find
studies on the same nutrient reporting different, and at times,
completely conflicting outcomes. Second, a common theme
found in the analysis is that strength of the evidence varies
depending on study design. While case-control studies are
more likely to find a significant association between the
nutrient of interest and the outcome of pancreatic cancer,
these significant associations rarely ever hold in cohort
studies. It is important to note that cohort studies are
considered to have a stronger and more robust design, free
of some of the serious limitations that accompany the case-
control studies. Because dietary intake is measured after
disease diagnosis, case-control studies suffer from limitations
such as recall bias, reverse causality, and surrogate reporting.
Although study design is a significant source of conflicting,
inconclusive results, measurement error and confounding
variables are serious limitations of epidemiological studies,
regardless of design. Both case-control and cohort studies
generally assess dietary intake using food frequency ques-
tionnaires, which have long been shown to be replete with
inaccuracies and limitations [66]. In fact, some epidemiol-
ogists have called into serious question the validity of
these questionnaires [67], arguing that it is time to abandon
their use as a means of assessing the intake of specific
nutrients, especially when attempting to assess their
association with diseases as complex as cancer [68].
Although these scientists purport that 7 day food diaries
may potentially circumvent the limitations of the food
frequency questionnaire, even these may not adequately
reflect long-term intake [69]. Even in the one study cited
that measured dietary intake using a 7-day food diary,
results of serum levels of vitamin C in the same study still
conflicted with measures of dietary intake using the 7-day
food diary, with the former indicating an inverse associa-
tion with pancreatic cancer, and the latter showing no
association [19]. This suggests that assessing dietary intake
through the currently available methods may not be
appropriate for measuring intakes of specific nutrients,
and that future research on specific nutrients should opt
for more objective biomarkers of nutritional status.
Another important issue for consideration with regards to
attempting to associate the dietary intake of select nutrients
with pancreatic cancer risk is the fact that these nutrients are
not commonly consumed (nor do they naturally exist) in
isolation. Given the high correlation of various nutrients
within a particular food, attempting to identify the specific
nutrient responsible for a reduced risk of disease through
epidemiological studies assessing dietary intake is rather
questionable [70]. Nutrients present in a given food are not
only highly correlated, but they also appear to act synergis-
tically, having additive and potentially compounding effects
on health [71]. The milieu in which a nutrient exists within a
food, known as the food matrix, may also impact the
physiological effect of that nutrient, suggesting that the unit
of interest in nutritional research should be the food, and not
a specific nutrient [72].
A related consideration that may affect the analysis of the
studies and contribute to the confusion in the literature is
that in some cases there is a lack of clear distinction on
whether the select nutrient measured included intake
through food, supplementation, or a combination of the two.
This distinction is critical since, as just mentioned, nutrients
ingested as part of a food matrix can be absorbed differently
than a nutrient given as a supplement.
3.2. Foods and pancreatic cancer risk
We next reviewed the evidence on some of the most
commonly studied foods and their impact on the risk of
pancreatic cancer. Many studies have been conducted on
various foods, including red and processed meat, dairy
products, fruits and vegetables, whole grains, alcoholic
beverages, and high glycemic foods (Table 2). In the sections
below, we summarize the most relevant findings for each of
the foods mentioned and discuss the limitations of the
evidence.
3.2.1. Red and processed meat
Red meat, barbequed or cooked at high temperatures,
contains heterocyclic amines (HCAs) which have been
shown to be mutagens associated with pancreatic cancer
[73]. Additionally, advanced glycation end products (AGEs)
found in red meat cooked at high temperatures have been
hypothesized to cause chronic inflammation, explaining
their possible association with pancreatic cancer [74]. Also,
N-nitroso compounds (NOCs), found in processed meats, are
known carcinogens that increase the risk of pancreatic
cancer [75], as may be the nitrite preservative [76].
The most recent and inclusive meta-analysis of 28 studies
involving red and processed meat consumption reports a
significant positive association for red meat in case-control
studies, but not cohort studies [77]. When stratifying by sex,
however, a significant positive association persists in men for
red and processed meat consumption in cohort studies as
well. A dose–response analysis indicates an 11% increased
risk of pancreatic cancer for every 100 g/day of red meat, but
no association for every 50 g/day of processed meat con-
sumption [77]. An earlier meta-analysis of only prospective
studies did reveal, however, a 19% increase in pancreatic risk
for every 100 g of processed meat consumed daily [78]. It is
important to carefully interpret these data, based on possible
confounders. For instance, high red meat eaters tend to also
have high alcohol intake and as mentioned in the introduc-
tion, high alcohol intake is associated with higher pancreatic
cancer risk. Thus, it remains unclear whether the observed
associations are fully attributable to red meat intake itself,
because of potential residual confounding by unadjusted
dietary factors, such as alcohol consumption, that co-vary
with red meat intake.
 N U TR IT ION RE S EA R CH 5 2 ( 20 1 8 ) 1 –1 3 7

3.2.2. Dairy products 3.2.4. Whole grains

Dairy products contain nutrients that have been hypothe-
sized to either promote or prevent carcinogenesis. Dairy
products naturally contain calcium and have been fortified
with vitamin D, which has been hypothesized to play a role in
preventing carcinogenesis [41,42]. On the other hand, dairy
products may also contain hormones and growth factors,
which can promote tumor growth [79-81].
Given this potential dual nature of dairy foods, it is not
surprising that epidemiological evidence is inconsistent and
conflicting. A pooled analysis of 14 cohort studies found no
association between pancreatic cancer risk and the intake of
total milk, whole milk, low fat milk, cheese, cottage cheese,
ice cream, or yogurt [82].
3.2.3. Fruits and vegetables
Fruits and vegetables contain many nutrients and phyto-
chemicals that have antioxidant, anti-mutagenic and anti-
carcinogenic properties [83-85]. The aforementioned vitamins
C, E, and folate as well as the carotenoids can be found in rich
quantities in many to most fruits and/or vegetables. In
addition, isothiocyanates, phytochemicals found in crucifer-
ous vegetables are powerful inducers of the detoxification
enzymes, which assist in the removal of potentially carcino-
genic substances. Similarly, fiber present in fruits and
vegetables can bind carcinogens, lower inflammatory
markers in circulation [86], and improve insulin metabolism
[87], dysregulation of which is associated with pancreatic
cancer [47,79,81].
The most recent and inclusive meta-analysis of 24 studies
assessing the association between fruit and vegetable intake
and pancreatic cancer risk found an inverse association,
which was significant in case-control studies and borderline
significant in cohort studies [88]. When stratifying by geo-
graphic location, this correlation was only significant for
vegetables in North America, whereas it was significant for
both fruit and vegetables in Asia. A meta-analysis of 9 studies
assessing specifically cruciferous vegetable intake found a
significant inverse association for the highest intake of
cruciferous vegetables, which remained significant in case-
control studies, but did not persist in cohort studies [89]. This
relationship was also most significant in studies conducted in
the United States.
Whole grains share some of the beneficial nutrients found in
fruits and vegetables previously discussed: mainly fiber,
vitamin E, and folate, and for these reasons, there are
biologically plausible mechanisms by which they may reduce
the risk of pancreatic cancer. Additionally, whole grain intake
has been associated with a reduced risk of diabetes [90], an
established risk factor for pancreatic cancer [58].
Given this association with diabetes, it is surprising that
the relationship of whole grains to pancreatic cancer has only
been assessed in a little more than a handful of case-control
studies, and 1 cohort study to date. A meta-analysis of these 8
studies indicates an inverse association for the highest levels
of whole grain consumption, which is statistically significant
only for the case-control studies [91]. No association was
found in the cohort study.
3.2.5. High glycemic foods
As previously discussed, insulin resistance and type II diabetes
have been associated with an increased risk of pancreatic
cancer [58]. There also have been associations made between
diabetes and foods high in glycemic index or glycemic load, as
well as the post-prandial glycaemia that results after con-
sumption of such foods [92]. Moreover, some studies have
found an association between high blood glucose levels and
the incidence of pancreatic cancer, particularly in women [93].
Fructose-sweetened beverages have also been found to induce
insulin resistance in overweight or obese individuals [94].
Despite the biological plausibility of this association, a
comprehensive meta-analysis of prospective studies found
no association between pancreatic cancer and glycemic
index, glycemic load, total carbohydrate intake, as well as
sucrose in both their high versus low and dose–response
analyses [95].
Aune et al observed, however, a significant positive
association for highest levels of fructose consumption, as
well as a 22% increased risk for every 25 g/day of fructose
consumed [95]. There are some speculations regarding the
mechanism on how fructose may increase pancreatic cancer
risk. These include: (a) the contribution of fructose to nucleic
acid synthesis through the pentose phosphate pathway
(catalyzed by an activation of the transketolase enzyme),
which is greater than glucose [96]; and as previously

Table 2 – Associations between foods and pancreatic cancer risk

Food Association with pancreatic cancer risk Reference(s)

Red and processed meat Positive association (remains significant after [77,78]
stratification only in case control studies for
both sexes; remains significant in cohort studies for men)
Dairy products No association [82]
Fruits and vegetables Inverse association (only borderline significant in cohort studies) [88,89]
Whole grains Inverse association (only significant in case control studies) [91]
High glycemic foods No association for glycemic load, glycemic index, [95]
total carbohydrate intake, and sucrose.
Positive association for highest levels of fructose consumption
Alcoholic beverages Positive association for heavy drinkers [102,103]
8 N U TR IT ION RE S EA R CH 52 ( 20 1 8 ) 1 –1 3
mentioned (b) chronic fructose feeding to mice leads to an
increase in insulin resistance and obesity [97]. Thus, fructose,
which is mainly ingested in the form of high fructose corn
syrup in processed foods and drinks, may increase pancreatic
cancer risk. However, this finding of an increased risk with
fructose intake warrants further investigation in studies with
better adjustment for confounding factors.
3.2.6. Alcoholic beverages
Although alcohol itself has been classified as a Group 1
carcinogen [98], it is thought that its metabolites, such as
acetaldehyde, may be more directly involved in carcinogen-
esis. With regards to pancreatic carcinogenesis, long-term
alcohol consumption may be associated with chronic pancre-
atitis, a known risk factor for pancreatic cancer [99,100].
Additionally, acetaldehyde and other fatty acid ethyl esters
produced from ethanol in pancreatic acinar cells may result in
inflammation of the pancreas [100].
Several meta-analyses have been conducted to assess the
association between alcohol consumption and the risk of
pancreatic cancer. One meta-analysis included a total of 32
studies and found an increased risk of pancreatic cancer for
those who consumed 3 or more drinks a day [1.22 (95% CI,
1.12-1.34)], and no increase in risk for those who consumed
less than 3 drinks a day [101]. The increased risk for heavy
drinkers remained, and was in fact stronger, in the cohort
studies. Similar results of increased association for heavy
drinking were reported in two more recent (2016-2017) meta-
analyses [102,103]. On the other hand, a smaller meta-
analysis of five case-control studies conducted in China failed
to find an association between alcohol consumption and
pancreatic cancer risk [104]. Limitations of this study,
however, include the small number of studies analyzed, as
well as the type of study included (case controls only) and the
specific study population. Finally, a large cohort study (not
included in any of the meta-analyses) found that alcohol
consumption was associated with earlier onset of pancreatic
cancer, and this effect was seen most strongly in heavy
drinkers [105]. Thus, based on the above, there appears to be a
link between heavy alcohol consumption and the risk of
pancreatic cancer, implying that a threshold effect may be at
play, where an effect is only seen once a certain level of
alcohol consumption is reached.
3.2.7. Discussion: foods and pancreatic cancer risk
The current evidence on foods and their association with
pancreatic risk yields a few more consistent results than the
literature on individual nutrients, but still leaves much to be
desired in terms of clear, unequivocal associations. Granted,
there does appear to be a positive association with the intake
of red and processed meat, for men in particular [77], a
positive association with alcohol in heavy drinkers, and a
possible inverse association with the consumption of fruits
and vegetables, particularly in Asian countries [88]. However,
the associations for other foods with biologically plausible
mechanisms for increasing or decreasing the risk of pancre-
atic cancer are overwhelmingly weak or null, particularly
when looking at prospective cohort studies [82,91,95].
In agreement with our previous discussion, this could be
largely due to the measurement error inherent in the food
frequency questionnaires used by these studies, and their
subsequent questionable validity [66-68]. This could also be
due to the numerous confounding variables present in such
studies and the difficulty in adequately controlling for them
[106]. Potential confounders in these nutritional studies
include other foods consumed by the individual [107]. For
example, with respect to foods, an individual who consumes
a greater amount of red meat may also consume more alcohol
and/or fructose-sweetened beverages and less fruits, vegeta-
bles, and whole grains, rendering it difficult to pinpoint which
food (whose presence or absence) may be contributing to the
association. Moreover, foods are also often consumed in
combination with other foods, if not at a given meal, at least
throughout a given day or week. This observation points,
again, to the idea of food synergy, in which different foods
(like nutrients) may interact to impact physiology in a way
that is different than when consumed in isolation.
3.3. Dietary patterns and pancreatic cancer risk
The above findings and analysis suggest that one's dietary
pattern may be more indicative of disease risk, as the effect of
a dietary pattern may be greater than the sum of its
constituent foods [108]. Of the variety of dietary patterns
characteristic of an individual's eating behavior, nutritionists
often divide them into two broad categories, known as the
Western-style dietary pattern and the prudent/healthy die-
tary pattern (Table 3). Similar in composition to the prudent
pattern, the Mediterranean diet has also garnered much
research interest for its favorable associations with reduction
in disease risk. In the sections below, we summarize the most
relevant findings for each of the dietary patterns mentioned
and discuss the implications and limitations of the evidence.
3.3.1. Western-style dietary pattern
A Western-style dietary pattern is characterized by high
intake of red or processed meats, refined grains, sweets,
high fat dairy products, potatoes, and low intake of fruits and
vegetables [102]. A meta-analysis which included 18 studies
that considered dietary intake consistent with a Western-
style diet found a significant positive association for those in
the highest category of intake of foods in the Western-type
dietary pattern compared to those in the lowest category of
intake (OR, 1.24; 95% CI, 1.06-1.45; P = .008) [102].
3.3.2. Prudent or healthy dietary pattern
A prudent or healthy dietary pattern is characterized by high
intakes of fruits, vegetables, whole grains, olive oil, fish, soy,
poultry, and low fat dairy [102]. The aforementioned meta-
analysis included 17 studies that assessed a prudent or
healthy dietary pattern and found a reduced risk of pancreatic
cancer (OR, 0.85; 95% CI, 0.77-0.95; P = .004) for those in the
highest category of intake of these foods as compared to those
in the lowest category of intake [102].
3.3.3. Healthy Eating Index
One of the cohort studies included in the previous meta-
analysis [102] assessed adherence to the 2005 Dietary Guide-
lines for Americans [109]. Using the Healthy Eating Index to
score adherence to a high quality diet composed of fruit,
 N U TR IT ION RE S EA R CH 5 2 ( 20 1 8 ) 1 –1 3
vegetables, grains, legumes, and low fat dairy and meat, this
study found a reduced risk of pancreatic cancer for those in
the highest categories of compliance (HR, 0.85; 95% CI, 0.74-
0.97) [109].
3.3.4. Mediterranean Diet
Although one of the case-control studies in the meta-analysis
of dietary patterns [102] assessed adherence to the Mediter-
ranean diet (MD), very few prospective studies have exclu-
sively examined adherence to a MD diet and its association
with pancreatic cancer risk. One cohort study calculated a
non-alcohol MD score (arMED) based on 8 dietary components
with high scores indicating a high consumption of fruits,
vegetables, legumes, fish, olive oil, and cereals (both white
and non-white) and low consumption of meat and dairy
products [110]. This prospective study conducted in 10
European countries with over 500 000 participants failed to
find a significant association between arMED score and
pancreatic cancer risk, but did find a borderline significant
association in Southern European cohorts, who tended to
have higher arMED scores [110]. Another prospective study
conducted in North Sweden calculated a MD score based on
similar criteria with a few slight differences [111]. This study,
which lasted for 18 years, included alcohol intake, only
considered whole-grain intake versus refined grains, and
took into consideration the ratio of MUFA and PUFA to SFA.
A significant reduction in mortality due to pancreatic cancer
was found [HR, 0.82 (95% CI, 0.68-0.99)] in men with highest
level of adherence to the MD diet according to these criteria as
compared to those with the lowest level of adherence.
3.3.5. Discussion: dietary patterns and pancreatic cancer risk
Although the number of studies are fewer, the evidence
analyzed indicates that dietary patterns are more significant-
ly associated with pancreatic cancer risk, with a healthy or
prudent pattern decreasing risk and a Western-style diet
increasing risk. The evidence for a link between the MD diet
and pancreatic cancer is sparser, with insufficient studies to
conduct a large meta-analysis. Despite this, analysis of the
cohort study that failed to detect an association brings up an
interesting point worth commenting on [110]. Although no
significant association was detected overall, a borderline
significant association was detected in populations that
tended to score higher with respect to adherence to a MD
diet. It is conceivable that with more extreme variation in the
adherence to a MD diet in the studied population, as may
Table 3 – Associations between dietary patterns and
pancreatic cancer risk
Dietary patterns Association with References(s)
pancreatic cancer risk
Western-style Positive association [102]
(OR, 1.24; 95% CI,
1.06-1.45; P = .008)
Prudent or healthy Reduced risk of [102]
pancreatic cancer
(OR, 0.85; 95% CI,
0.77-0.95; P = .004)
9
have been possible in the Southern European cohort in the
EPIC study or in the Swedish study [111], associations are
more likely to become evident.
Additionally, as it has been pointed out, although food
frequency questionnaires are rather crude measures, they
may be adequate enough to detect broader measures of
consumption as in these dietary pattern analyses [68]. These
dietary patterns, reflecting more realistically an individual's
dietary intake and the complexity of the synergies between
nutrients in foods, and foods in combination with each other,
are also more significantly associated with disease risk
[71,108].
It is interesting to note that the associations seen in these
meta-analyses of dietary patterns are not as dramatic as one
might expect, especially when considering the large estimat-
ed attribution of pancreatic cancer cases to dietary causes
[6,8]. As pointed out above, this may be due to the weakness of
current dietary assessment tools to accurately detect the
magnitude of associations as they truly are [68]. This could
also be due to the difficulty in controlling for confounding
variables, as previously discussed [106]. Although many
studies attempt to statistically control for other risk factors
for pancreatic cancer such as smoking, obesity, and diabetes,
the statistical controls applied are far from perfect and may
leave behind a residual confounding. Moreover, many studies
do not adequately control for all confounding variables, nor
can it be assumed that all possible confounders have been
recognized.
4. Conclusion
Given that there are no current screening recommendations
for pancreatic cancer, primary prevention is of utmost impor-
tance. Therefore, a better understanding of the etiology and
risk factors, including dietary risk factors, is essential for the
primary prevention of this disease. Following our thorough
analysis of the evidence on this topic, a key trend emerges. As
we advance from individual nutrients to foods to dietary
patterns, the evidence of certain associations with pancreatic
cancer risk becomes clearer, has more power, and is less
conflicting. This supports the notion of food synergy and
prompts a more holistic approach to studying dietary risk.
5. Knowledge gaps and future research directions
Our analysis of the data revealed a number of limitations and
gaps in our current knowledge of dietary factors and
pancreatic cancer risk. Below, we describe some of these
limitations and suggest avenues for future research to further
our understanding in this critical area. First, in the meta-
analyses reviewed assessing the association of nutrients and
foods to pancreatic cancer risk, it was common to find that
statistically significant results only remain significant after
stratification in case control studies. Due to this, we empha-
size the need to focus future research on epidemiological
associations by using the more robust prospective cohort
design. This will lend more credence to any associations
10 N U TR IT ION RE S EA R CH 52 ( 20 1 8 ) 1 –1 3
found. Second, with respect to nutrients, many studies report
conflicting results, and this may be due in part to the
inadequacy of food frequency questionnaires to accurately
estimate dietary intake of the nutrients of interest. We
therefore propose that food frequency questionnaires no
longer be used as tools to assess nutrient intake, and that
more accurate and objective markers of nutritional status be
developed, validated, and utilized. Third, given the role of the
food matrix and the concept of food synergy, we generally
discourage a heavy focus on assessing the association of
specific nutrients with pancreatic cancer risk. This does not
suggest that it is not important to study individual nutrients
or specific foods. In fact, experimental studies, whether in
vitro or in vivo, are valuable in elucidating the mechanisms by
which certain nutrients affect physiological or pathophysio-
logical states, and may assist in developing therapeutic
approaches. Thus, there is an urgent need for further
experimental studies to research the role of nutrients in this
context.
In other words, it appears unwise to continue devoting
time, effort, and funds into determining specific nutrient-
disease associations through epidemiology for the purposes
of public health recommendations. It is highly unlikely that
one or two specific nutrient deficiencies are the culprits
behind the pandemic of such a highly complex and multifac-
torial disease as pancreatic cancer. Rather, it is likely a
combination of a number of nutrient deficiencies/excesses
along with oxidative stress or inflammation imposed by other
dietary choices, better reflected in the dietary pattern, that are
contributing to this disease process.
Given that diet is only one aspect of a lifestyle that
contributes to the risk of pancreatic cancer, it appears critical
to consider diet within the context of other lifestyle and
established risk factors, such as smoking, obesity, physical
inactivity, and excessive alcohol consumption [9]. For exam-
ple, the NIH-AARP Diet and Health study assessed the risk of
pancreatic cancer based on lifestyle score and prospectively
followed close to 500 000 participants for approximately 7
years [112]. The highest lifestyle score possible in their study
was 5, which indicated that the individual never smoked or
ceased at least 10 years ago, engaged in at least 20 minutes of
vigorous activity 3 to 4 times per week, had limited alcohol
consumption, a healthy BMI, and adhered to a MD type diet. A
58% reduction in pancreatic cancer risk was observed when
comparing those with the highest score (5) to those with the
lowest (0). Similarly, a 46% reduction in risk was noted for
those in the two highest score categories (4-5) as compared to
those in the lower categories (0-1). These dramatic and
significant associations represent compelling evidence that
we cannot truly separate diet alone as a causative factor in
the etiology of pancreatic cancer.
In fact, as previously mentioned, pancreatic cancer
presents multiple risk factors, which may have an additive
or compounding effect or interaction with each other.
Established risk factors include diabetes, pancreatitis,
smoking, heavy drinking, and Helicobacter pylori infection [9],
whereas others may be yet to be officially recognized or even
discovered. These may include exposure to environmental
toxins [113,114], chronic stress [115], or even the effects of our
food system, both locally and globally [116,117]. Therefore, we
propose that future epidemiological research studies, espe-
cially prospective cohort studies, should focus on how a
combination of these various factors may interact with
dietary patterns to promote carcinogenesis of the pancreas.
Finally, and perhaps even more importantly, we see the
need for future research to determine the most effective
evidence-based strategies for the implementation of what is
already known. We call for an increase in nutrition and
disease prevention education in our health science programs,
so physicians and nurses can encourage dietary and lifestyle
practices that are known to reduce the risk of disease. Efforts
to assist and make accessible to individuals and communities
the practice of the known healthy lifestyle choices are
paramount [118]. Further research should be devoted to
determining the best evidence-based practices in this area.
Not only does this have the potential to reduce the incidence
of pancreatic cancer specifically, but numerous other chronic
diseases as well.
Acknowledgment
This work was supported by funds from the University of
California, Davis to G.G.M. The authors declare no conflict of
interest.
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