Lower Risk Of Pancreatic Cancer Research Articles

Life's Essential 8, genetic susceptibility, and risk of incident pancreatic cancer: A prospective cohort study.

The association between the American Heart Association (AHA) Life's Essential 8 (LE8) and the risk of pancreatic cancer (PC) remains unclear. Our goal was to assess the relationships between LE8, genetic susceptibility, and PC risk. This cohort consisted of 234,102 participants from the UK Biobank. The components of LE8 include diet, nicotine exposure, sleep, physical activity, blood glucose, body mass index, blood lipids, and blood pressure. LE8 is classified into three categories: low cardiovascular health (CVH), moderate CVH, and high CVH. Measurements were made using Cox proportional risk models to estimate impact of associations between LE8, genetic susceptibility, and incidence of PC in participants. Compared to participants with low LE8 scores, those with moderate and high LE8 scores had a 53% (HR, 0.47; 95% CI, 0.39-0.57) and 70% (HR, 0.30; 95% CI, 0.22-0.41) lower risk of developing PC, respectively. Interestingly, among individuals with high genetic risk, high LE8 scores were associated with greater benefits (HR, 0.24; 95% CI, 0.15-0.40), whereas the protective effect was weaker among those with low genetic risk (HR, 0.40; 95% CI, 0.21-0.75). Participants with a high LE8 score and a low polygenic risk score (PRS) had the lowest risk of PC (HR, 0.19; 95% CI: 0.11-0.33). Furthermore, we observed a significant additive interaction between LE8 and PRS. A higher LE8 score is associated with a lower risk of PC, especially for participants with a high PRS. These findings have important implications for participants most genetically predisposed to PC and for targeted strategies for PC prevention.

The Relationship between Statin Intake and Risk of Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Pancreatic neoplasm is one of the types of cancer with a high incidence and case-fatality rate. This study was designed to investigate the relationship between statin intake and the risk of pancreatic cancer with a systematic review and meta-analysis approach. This study was a systematic review and meta-analysis of studies published before 2023 in Cochrane Library, Web of Science (WOS), PubMed, Google Scholar, ScienceDirect, Scopus, and Embase databases. The statistical analyses were conducted using Stata software, version 15. The significance level for this study was set at 0.05. This meta-analysis included 32 studies and a total of 5,849,814 participants. The risk ratio (RR) of pancreatic cancer in comparison to the non-statin receiving group in statin users in total was equal to 0.75 (95% CI: 0.66-0.86, p-value <0.001), in the cohort studies was obtained to be 0.70 (0.53-0.93), in the randomized clinical trials (RCTs) had a ratio of 0.99 (0.53-1.86), while studies conducted in American countries had a ratio of 0.69 (0.51-0.93), studies in Asian countries had a ratio of 0.73 (0.56-0.97), and studies in European countries had a ratio of 0.88 (0.76-1.02). Furthermore, the study did not detect any signs of publication bias. The study findings suggest a potential connection between using statins and a lower risk of pancreatic cancer. However, it is important to note that controlled clinical trials did not find a statistically significant association between taking statins and the development of pancreatic cancer. Therefore, it is advisable to exercise caution when interpreting the results of this study.

Dietary patterns in relation to incidence rate of pancreatic cancer - the Norwegian women and cancer cohort study.

Despite development in cancer treatment and prevention options during the past few years, cancer of the pancreas remains a diagnosis associated with poor prognosis and limited options for prevention. Diet has proven to be an important risk factor for development of many types of cancer, particularly for cancers of the digestive system. Still, evidence regarding its relation to pancreatic cancer remains ambiguous. To investigate the relationship between diet and pancreatic cancer, an analysis of dietary patterns in participants from the Norwegian Women and Cancer Study (n = 89,156; 305 pancreatic cancer cases) was performed. Cox regression analysis was used for studying possible associations between dietary patterns, derived from principal component analysis, and pancreatic cancer incidence. The four most prominent dietary patterns were identified and described: European pattern, animal food consumers' dietary pattern, traditional Norwegian pattern, and alcohol-abstaining dietary pattern. In analysis without adjustment for confounders, being in the highest tertile of the abstaining dietary pattern was associated with lower risk of pancreatic cancer in comparison to the lowest tertile (hazard ratios [HR]: 0.66, 95% confidence interval [CI]: 0.49-0.89). After additional adjustment for height and smoking status, no dietary pattern was associated with increased pancreatic cancer risk, nor was there any difference in effect estimates between strata of smokers and non-smokers. The results of our current analysis do not support the role of major dietary patterns in the development of pancreatic cancer.

Dietary Factors and Pancreatic Cancer Risk: An Umbrella Review of Meta-Analyses of Prospective Observational Studies.

Dietary factors may be associated with the occurrence of pancreatic cancer. This umbrella review aimed to review and grade the evidence for the associations between dietary factors and pancreatic cancer risk. We searched PubMed, EMBASE, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and CINAHL for eligible literature. We included meta-analyses of randomized controlled trials (RCTs) or prospective observational studies. We used AMSTAR-2, a measurement tool to assess systematic reviews, to evaluate the methodological quality of the included meta-analyses. For each association, we calculated the summary effect size, 95% CI, heterogeneity, number of cases, 95% prediction interval, small-study effect, and excess significance bias. The protocol for this review was registered in the PROSPERO database (CRD42022333669). We included 41 meta-analyses of prospective observational studies describing 59 associations between dietary factors and pancreatic cancer risk. None of the retrieved meta-analyses included RCTs. No association was supported by convincing or highly suggestive evidence; however, there was suggestive evidence of a positive association between fructose intake and pancreatic cancer risk. There was weak evidence for an inverse association of nuts intake or adherence to the Mediterranean diet with pancreatic cancer incidence, and for positive associations between a higher intake of red meat or heavy alcohol intake and pancreatic cancer incidence. The remaining 54 associations were nonsignificant. Consistent with the American Institute for Cancer Research review, this umbrella review found that regular consumption of nuts and reduced intake of fructose, red meat, and alcohol were associated with a lower risk of pancreatic cancer. Emerging weak evidence supported an inverse association between adherence to the Mediterranean diet and pancreatic cancer risk. As some associations were rated as weak and most were considered nonsignificant, further prospective studies are needed to investigate the role of dietary factors and risk of pancreatic cancer.

Plant-based diets and the risk of pancreatic cancer: a large prospective multicenter study

BackgroundPlant-based diets have been recommended for improving health outcomes, including cancer. However, previous studies on plant-based diets and the risk of pancreatic cancer are scarce and fail to consider plant food quality. ObjectivesWe sought to examine the potential associations of 3 plant-based diet indices (PDIs) with the risk of pancreatic cancer in a US population. MethodsA population-based cohort of 101,748 US adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The overall PDI, healthful PDI (hPDI), and unhealthful PDI (uPDI) were constructed to qualify adherence to overall, healthy, and less healthy plant-based diets, respectively, with higher scores indicating better adherence. Multivariable Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was conducted to identify the potential effect modifiers. ResultsOver a mean follow-up of 8.86 years, 421 pancreatic cancer cases occurred. Participants in the highest compared with the lowest quartiles of overall PDI had a lower risk of pancreatic cancer [HRquartile 4 versus 1: 0.74; 95% confidence interval (CI): 0.57, 0.96; Ptrend = 0.023]. A stronger inverse association was observed for hPDI (HRquartile 4 versus 1: 0.56; 95% CI: 0.42, 0.75; Ptrend < 0.001). Conversely, uPDI was positively associated with the risk of pancreatic cancer (HRquartile 4 versus 1: 1.38; 95% CI: 1.02, 1.85; Ptrend = 0.012). Subgroup analyses revealed a stronger positive association for uPDI in participants with BMI <25 (HRquartile 4 versus 1: 3.22; 95% CI: 1.56, 6.65) than in those with BMI ≥25 (HRquartile 4 versus 1: 1.08; 95% CI: 0.78, 1.51) (Pinteraction = 0.001). ConclusionsIn this US population, adherence to a healthy plant-based diet confers a lower risk of pancreatic cancer, whereas adherence to a less healthy plant-based diet confers a higher risk. These findings highlight the importance of considering plant food quality in preventing pancreatic cancer.

Adherence to Mediterranean Diet and Risk of Pancreatic Cancer: Systematic Review and Meta-Analysis.

Pancreatic cancer (PC) represents the 6th cause of cancer death. Although the aetiology of PC is not completely understood, numerous risk factors have been identified in association with this cancer, among them diet. However, little is known about the association between the Mediterranean Diet (MedDiet) and the risk of PC. For this reason, we conducted a systematic review with meta-analysis according to the PRISMA guidelines, searching on three databases (PubMed/MEDLINE, Scopus, and EMBASE). The protocol was registered in PROSPERO. Both fixed and random effect models were performed. The Effect size was reported as a hazard ratio (HR) with a 95% Confidence Interval (CI). A total of eight articles were included. The methodological quality of the included meta-analyses was high. Our results show that a higher adherence to the MedDiet is associated with a lower risk of PC [HR:0.82 (0.76-0.88) p < 0.001, based on 1,301,320 subjects]. The results were also confirmed in sensitivity and subgroups analyses (avoidance of potential overlapping effects, type of tools used to assess dietary intake and the diagnosis of PC, prevalence and incidence of PC risk, country where the studies took place, sex, and cancer site). Promoting a higher adherence to the MedDiet could be an effective approach to reduce the risk of PC.

Dietary Inflammatory Index, Alternative Healthy Eating Index-2010, Mediterranean Diet Score and the risk of pancreatic cancer

BackgroundPrevious studies of dietary patterns and pancreatic cancer risk have been inconclusive; we aimed to investigate the association of Mediterranean Diet Score (MDS), Alternative Healthy Eating Index-2010 (AHEI-2010), and Dietary Inflammatory Index (DII®) with risk of pancreatic cancer. MethodsWe used data from the Melbourne Collaborative Cohort Study including 33,690 men and women aged 40–69 years at recruitment in 1990–1994. A total of 258 incident cases of pancreatic cancer was identified over an average of 23.7 years of follow-up. Hazard ratios (HR) were estimated using Cox regression, with age as the underlying time metric, adjusting for potential confounders including sex, height, country of birth, education, socio-economic position, physical activity, energy intake, smoking status, pack-years smoking, years since quitting smoking, and alcohol intake. ResultsA healthier diet as assessed by the AHEI-2010 was associated with a lower risk of pancreatic cancer [HRQuartile4 vs Quartile1 = 0.58; 95%CI 0.40 – 0.85; p for trend 0.003]. Weaker but consistent evidence was observed for the other indexes [DII® HRQuartile4 vs Quartile1 = 1.30; 95%CI 0.82 – 2.06; p for trend 0.1], [MDS HRCategory3 vs Category1 = 0.79; 95%CI 0.49 – 1.26; p for trend 0.06]. ConclusionAdherence to a healthier diet, as assessed by the AHEI-2010, may reduce the risk of pancreatic cancer.

Diets, Dietary Patterns, Single Foods and Pancreatic Cancer Risk: An Umbrella Review of Meta-Analyses.

Pancreatic cancer (PC) represents the third leading cause of cancer death in 2020. Despite the fact that, in 2018, the World Cancer Research Fund report concluded that there is still a lack of evidence on the role of foods or diets and risk for PC, a flourishing body of evidence has been published and needs to be analyzed. For this reason, we conducted an umbrella review on the association between different dietary patterns/food components and PC. Data sources PubMed/MEDLINE, Scopus, Web of Science, EMBASE, and the Cochrane Collaboration were searched. The Joanna Briggs Institute Umbrella Review Methodology was used. The protocol was registered in PROSPERO. A total of 23 articles were included, covering a wide range of dietary patterns/food components: healthy/prudent dietary patterns (n = 4), Mediterranean diets (MedDiet) (n = 1), plant-based diets (n = 2), the Dietary Inflammatory Index (DII) (n = 2), western diets (n = 2), and, lastly, unhealthy diets (n = 2). Regarding dietary components, the following were assessed: total fruit (n = 2), citrus fruit (n = 1), total vegetables (n = 2), cruciferous vegetables (n = 1), red meat (n = 6), processed meat (n = 4), poultry (n = 2), eggs (n = 1), fish (n = 5), whole grain (n = 2), potato (n = 1), and nuts (n = 2). The methodological quality of the included meta-analyses was generally low or critically low. Although the strength of evidence was generally weak, convincing or suggestive evidence was found for a healthy/prudent, plant-based diet, fruit and vegetables, and lower risk of PC, whereas a high intake of red meat was associated with a higher risk of PC at a convincing level of evidence. Further studies are needed to confirm the role of the other dietary patterns/food components and the risk of PC.

Composite Score of Healthy Lifestyle Factors and the Risk of Pancreatic Cancer in a Prospective Cohort Study

Abstract While the associations between individual lifestyle factors and risk of pancreatic cancer were studied extensively, their combined impact has not been examined. We evaluated the association of a composite score of healthy lifestyle factors, including body mass index, cigarette smoking, the Alternative Healthy Eating Index-2010 (AHEI-2010), sleep duration, and physical activity with pancreatic cancer risk in the Singapore Chinese Health Study, an ongoing prospective cohort study of 63,257 Chinese aged 45 to 74 years at enrollment in 1993 to 1998 with up to 25 years of follow up. Cox proportional hazard regression method was used to estimate HR and its 95% confidence interval (CI) with adjustment for multiple potential confounders. We identified 316 incident pancreatic cancer cases among the cohort participants after a mean 17 years of follow up. Individuals with higher composite scores representing healthier lifestyle were at significantly lower risk of pancreatic cancer. The multivariate-adjusted HRs (95% CIs) of pancreatic cancer incidence for the composite scores 2, 3, 4, 5, 6 to 7 were 0.60 (0.50–0.91), 0.48 (0.32–0.71), 0.45 (0.31–0.67), 0.41 (0.27–0.62), and 0.38 (0.24–0.62), respectively, compared with the scores 0 to 1 (Ptrend &amp;lt; 0.0001). The inverse association was more apparent among participants without diabetes history and was robust in men and women as well as in alcohol drinkers and nondrinkers. In summary, the association for pancreatic cancer risk was stronger for the aggregated than individual healthy lifestyle factors. These findings suggest that a more comprehensive lifestyle modification strategy would be more effective for prevention of pancreatic cancer than the change of a single lifestyle factor. Prevention Relevance: In this large prospective Asian study, we calculated a composite score of healthy lifestyle factors, including body mass index, cigarette smoking, the Alternative Healthy Eating Index-2010 (AHEI-2010), sleep duration, and physical activity and found this composite score was associated with a significant reduction in pancreatic cancer risk, by as much as 62%. This finding suggests that public health programs emphasizing comprehensive lifestyle modification strategy would be more effective for prevention of pancreatic cancer than the change of a single lifestyle factor.

Changes in Metabolic Syndrome Status are Associated With Altered Risk of Pancreatic Cancer: A Nationwide Cohort Study

Metabolic syndrome (MetS) is reversible; however, the effect of changes in MetS status on pancreatic cancer risk is unknown. We aimed to investigate the effects of changes and persistence in MetS status on pancreatic cancer risk. This nationwide cohort study included 8,203,492 adults without cancer who underwent 2 consecutive biennial health screenings provided by the Korean National Health Insurance System between 2009 and 2012 and were followed up until 2017. MetS was defined as the presence of 3 of its 5 components, which were evaluated at 2 consecutive biennial health screenings. Participants were categorized into the MetS-free, MetS-recovered, MetS-developed, or MetS-persistent group. Multivariable Cox proportional hazards regression models were used. During the 40,464,586 person-years of follow-up (median, 5.1 years), 8010 individuals developed pancreatic cancer. Compared with the MetS-free group, the MetS-persistent group had the highest risk of pancreatic cancer (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.23-1.37), followed by the MetS-developed group (HR, 1.17; 95% CI, 1.09-1.25) and the MetS-recovered group (HR, 1.12; 95% CI, 1.04-1.21) after adjusting for potential confounders (P for trend <.001). The MetS-recovered group was associated with a lower risk of pancreatic cancer than that in the MetS-persistent group (P < .001). The association between changes in MetS status and pancreatic cancer risk did not differ according to sex or obesity (all P for interactions >.05). In this study, recovering from MetS was associated with a reduced risk of pancreatic cancer compared with persistent MetS, suggesting that pancreatic cancer risk can be altered by changes in MetS.

Type 2 diabetes prevention diet and the risk of pancreatic cancer: A large prospective multicenter study

Type 2 diabetes prevention diet confers a lower risk of type 2 diabetes, which exhibits overlapping mechanisms with pancreatic cancer. We performed a prospective study to examine whether adherence to this dietary pattern is associated with a reduced risk of pancreatic cancer. A population-based cohort of 101,729 American adults was identified. A dietary diabetes risk reduction score was computed to reflect adherence to this dietary pattern, with higher scores representing greater adherence. Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Prespecified subgroup analyses were used to identify the potential effect modifiers. After an average follow-up of 8.86 years (900,871.67 person-years), a total of 402 pancreatic cancer cases were observed. In the fully adjusted model, participants in the highest quartile of dietary diabetes risk reduction score were found to have a reduced risk of pancreatic cancer compared with those in the lowest quartile [HRquartiles 4versus1: 0.62; 95% confidence interval (CI): 0.44, 0.86; Ptrend=0.004], which remained in a series of sensitivity analyses. Subgroup analyses further found that this favorable association was more pronounced in current or former smokers (HRquartiles 4versus1: 0.48; 95% CI: 0.30, 0.77) than in never smokers (HRquartiles 4versus1: 0.71; 95% CI: 0.44, 1.15), although the interaction test did not reach statistical significance (Pinteraction=0.095). Greater adherence to type 2 diabetes prevention diet is associated with a lower risk of pancreatic cancer in this US population. More studies are needed to confirm our findings.

Abstract 854: Dietary quality indexes and risk of pancreatic cancer: Findings from a prospective cohort study

Abstract Background. Dietary quality index represents a long-term dietary intake of nutritive and non-nutritive compounds. Therefore, it would be more informative for evaluating the association between dietary intake and health outcomes, including pancreatic cancer, in different populations with distinct dietary habits and patterns. Limited research has been conducted on the effect of dietary quality index (DQI) on pancreatic cancer risk in Asian populations. Methods. Using data from Singapore Chinese Health Study, a prospective cohort study of 63,257 Chinese men and women aged 45-74 at enrollment during 1993-1998, we created four diet-quality index scores: the Alternative Health Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH) and Heathy Diet Indicator (HDI) based on the baseline information collected using validated semi-quantitative food frequency questionnaire. After a mean 17 years of follow-up, 316 participants developed pancreatic cancer. The Cox proportional hazard regression method was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for pancreatic cancer in relation to different levels of these DQI scores. Results. High scores of AHEI-2010, aMED and DASH were associated with lower risk of pancreatic cancer (all Ptrend&amp;lt;0.05). Compared with the lowest quartile, HRs (95% CIs) of pancreatic cancer for the highest quartiles of AHEI-2010, aMED and DASH were 0.65 (0.46-0.90), 0.60 (0.41-0.89), and 0.69 (0.48-0.98), respectively, after adjustment for age, sex, body mass index, alcohol intake, tobacco smoking, and history of diabetes. We did not find a discernable heterogeneity in these dietary quality indexes-pancreatic cancer risk associations by body mass index levels or status of diabetes or smoking. Conclusion. High quality diet is significantly associated with reduced risk of pancreatic cancer. The consistent results across different DQIs support the notion that adherence to a healthy diet may lower the risk of pancreatic cancer, suggesting that dietary modification may be a cost-effective approach for primary prevention of pancreatic cancer. Funding: The Singapore Chinese Health Study was supported by the National Institutes of Health (NIH) of the United States (grants # R01 CA144034 and UM1 CA182876). HN Luu is partially supported by the University of Pittsburgh Medical Center Hillman Cancer Center start-up grant. P Paragomi was supported by the NIH T32CA186873 training grant in cancer epidemiology and prevention; W-P Koh was partially supported by the National Medical Research Council, Singapore (NMRC/CSA/0055/2013). Citation Format: Hung N. Luu, Pedram Paragomi, Aizhen Jin, Renwei Wang, Nithya Neelakantan, Rob M. van Dam, Randall E. Brand, Woon-Puay Koh, Jian-Min Yuan. Dietary quality indexes and risk of pancreatic cancer: Findings from a prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 854.

Dehydroepiandrosterone modulates oxidative DNA damage in pancreatic cancer: A case-control study.

Background and AimDehydroepiandrosterone (DHEA) has a protective role against several types of cancer, although its mechanisms of action are still unknown, it may be related to the antioxidant effect of DHEA. We hypothesized that DHEA has a preventive effect on the formation of the 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) DNA adduct in pancreatic cancer patients.MethodsSerum DHEAs were quantified by the ELISA method in 50 pancreatic cancer patients with histopathological diagnosis of adenocarcinoma and 50 matched controls. The amount of 8‐OHdG was assessed in peripheral blood leukocyte extracted DNA using a 32P‐DNA postlabeling technique.ResultsPancreatic cancer patients had lower serum DHEA levels than healthy controls, although it did not differ significantly. Instead, the 8‐OHdG DNA adduct was significantly higher in the case than in the control (P = <0.001). Remarkably, the negative correlation between 8‐OHdG and DHEA was distinguished between cases (P = 0.025, r = −0.315) but not in controls (P = 0.078, r = −0.250). In the crude and corrected estimate for pancreatic cancer risk, a significant protective effect of DHEA against pancreatic cancer was found with increasing DHEA when 8‐OHdG is greater than its median (adjusted OR = 0, 79, 95% confidence intervals [CI]: 0.66–0.94). Similarly, a lower risk of pancreatic cancer was observed in the third tertile of DHEA (adjusted OR = 0.05, 95% CI: 0.004–0.69).ConclusionsThese results indicate that serum DHEA reduces the risk of pancreatic cancer with an anti‐DNA damage effect. Hence, the influence of DHEA to prohibit the accumulation of 8‐OHdG may be one of its physiological functions.

Dietary Vitamin K Intake and the Risk of Pancreatic Cancer: A Prospective Study of 101,695 American Adults.

No epidemiologic studies have been conducted to assess the association of intake of dietary vitamin K with the risk of pancreatic cancer. We used prospective data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial between 1993 and 2009 to fill this gap. A total of 101,695 subjects were identified. Dietary intakes of phylloquinone (vitamin K1), menaquinones (vitamin K2), and dihydrophylloquinone (dihydrovitamin K1) were assessed using a food frequency questionnaire. Cox regression was applied to calculate hazard ratios and 95% confidence intervals. During a mean follow-up of 8.86 years (900,744.57 person-years), 361 cases of pancreatic cancer were documented. In the fully adjusted model, dietary intakes of phylloquinone (for quartile 4 vs. quartile 1, hazard ratio (HR)=0.57, 95% confidence interval (CI): 0.39, 0.83; P for trend =0.002) and dihydrophylloquinone (for quartile 4 vs. quartile 1, HR=0.59; 95% CI: 0.41, 0.85; P for trend =0.006), but not menaquinones (for quartile 4 vs. quartile 1, HR =0.93; 95% CI: 0.65, 1.33; P for trend =0.816), were found to be inversely associated with the risk of pancreatic cancer in a nonlinear dose-response manner (all P values for nonlinearity<0.05), and this was not modified by predefined stratification factors and remained in sensitivity analyses. In conclusion, dietary intakes of phylloquinone and dihydrophylloquinone, but not menaquinones, confer a lower risk of pancreatic cancer. Future studies should confirm our findings.

Whole-Grain Intake and Pancreatic Cancer Risk—The Danish, Diet, Cancer and Health Cohort

BackgroundPancreatic cancer is a highly deadly disease with a poor prognosis. There is limited knowledge about prevention of the disease; thus, identification of risk factors is important to reduce the disease incidence. ObjectivesThe aim of the present study was to prospectively investigate associations between incidence of pancreatic cancer and whole-grain intake measured in 2 ways: as whole-grain product intake (g whole-grain products/d) and as whole-grain intake (grams of whole grains/d). Moreover, the intake of subgroups of these was also investigated: whole-grain products (rye bread, whole-grain bread, and oatmeal/muesli) and cereals (rye, wheat, and oats). MethodsIn total, 55,995 Danish adults aged 50–64 y, of whom 446 developed pancreatic cancer (17.5 y mean follow-up), were included in the study. Detailed information on daily intake of whole-grain products was available from a validated self-administered FFQ, and intake of whole-grain cereals (wheat, rye, and oats) was estimated using information from a 24-h dietary recall. The association between the whole-grain exposures and incidence of pancreatic cancer was investigated by Cox regression analyses adjusted for potential confounders. ResultsTotal whole-grain product intake was associated with a 7% lower incidence of pancreatic cancer per serving (50 g/d) (HR: 0.93; 95% CI: 0.86, 1.00), and in the sex-specific analyses, an inverse association was found only in men. No association was found for total whole-grain intake (per 16-g serving size; HR: 0.96; 95% CI: 0.89, 1.03). When investigating specific whole-grain products and cereals individually, none were alone associated with lower incidence of pancreatic cancer. ConclusionOur findings indicate that intake of whole grains is associated with lower risk of pancreatic cancer in middle-aged men. Consuming ample amounts of whole grains may prove beneficial in terms of lowering pancreatic cancer risk.

Low-carbohydrate diets and the risk of pancreatic cancer: a large prospective cohort study.

Low-carbohydrate diets have become a popular approach for weight loss in recent years. However, whether low-carbohydrate diets are associated with the risk of pancreatic cancer remains to be elucidated. Hence, we examined the association of low-carbohydrate diets with the risk of pancreatic cancer in a US population. A population-based cohort of 95 962 individuals was identified. A low-carbohydrate-diet score was calculated to quantify adherence to this dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate risk estimate for the association of the low-carbohydrate-diet score with the risk of pancreatic cancer. Subgroup analysis was used to identify the potential effect modifiers. After an average follow-up of 8.87 years (875856.9 person-years), we documented a total of 351 pancreatic cancer cases. In the fully adjusted model, the highest versus the lowest quartiles of the overall low-carbohydrate-diet score were found to be associated with a reduced risk of pancreatic cancer (hazard ratioquartile 4 versus 1: 0.61; 95% confidence interval: 0.45, 0.82; Ptrend < 0.001). Subgroup analysis found that the inverse association of low-carbohydrate diets with the risk of pancreatic cancer was more pronounced in individuals aged ≥65 years than in those aged <65 years (Pinteraction = 0.015). Similar results were obtained for animal and vegetable low-carbohydrate-diet scores. In conclusion, low-carbohydrate diets, regardless of the type of protein and fat, are associated with a lower risk of pancreatic cancer in the US population, suggesting that adherence to low-carbohydrate diets may be beneficial for pancreatic cancer prevention. Future studies should validate our findings in other populations.

Docosahexaenoic acid inhibits the proliferation of Kras/TP53 double mutant pancreatic ductal adenocarcinoma cells through modulation of glutathione level and suppression of nucleotide synthesis.

The treatment of cancer cells obtained by blocking cellular metabolism has received a lot of attention recently. Previous studies have demonstrated that Kras mutation-mediated abnormal glucose metabolism would lead to an aberrant cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Previous literature has suggested that consumption of fish oil is associated with lower risk of pancreatic cancer. In this study, we investigated the anti-cancer effects of docosahexaenoic acid (DHA) in human PDAC cells in vitro and in vivo. Omega-3 polyunsaturated fatty acids (PUFAs) such as DHA and eicosapentaenoic acid (EPA) significantly inhibited the proliferation of human PDAC cells. The actions of DHA were evaluated through an induction of cell cycle arrest at G1 phase and noticed a decreased expression of cyclin A, cyclin E and cyclin B proteins in HPAF-II cells. Moreover, it was found that co-treatment of DHA and gemcitabine (GEM) effectively induced oxidative stress and cell death in HPAF-II cells. Interestingly, DHA leads to an increased oxidative glutathione /reduced glutathione (GSSG/GSH) ratio and induced cell apoptosis in HPAF-II cells. The findings in the study showed that supplementation of GSH or N-Acetyl Cysteine (NAC) could reverse DHA-mediated cell death in HPAF-II cells. Additionally, DHA significantly increased cellular level of cysteine, cellular NADP/NADPH ratio and the expression of cystathionase (CTH) and SLCA11/xCT antiporter proteins in HPAF-II cells. The action of DHA was, in part, associated with the inactivation of STAT3 cascade in HPAF-II cells. Treatment with xCT inhibitors, such as erastin or sulfasalazine (SSZ), inhibited the cell survival ability in DHA-treated HPAF-II cells. DHA also inhibited nucleotide synthesis in HPAF-II cells. It was demonstrated in a mouse-xenograft model that consumption of fish oil significantly inhibited the growth of pancreatic adenocarcinoma and decreased cellular nucleotide level in tumor tissues. Furthermore, fish oil consumption induced an increment of GSSG/GSH ratio, an upregulation of xCT and CTH proteins in tumor tissues. In conclusion, DHA significantly inhibited survival of PDAC cells both in vitro and in vivo through its recently identified novel mode of action, including an increment in the ratio of GSSG/GSH and NADP/NADPH respectively, and promoting reduction in the levels of nucleotide synthesis.

A prospective evaluation of serum methionine-related metabolites in relation to pancreatic cancer risk in two prospective cohort studies.

Deficiencies in methyl donor status may render DNA methylation changes and DNA damage, leading to carcinogenesis. Epidemiological studies reported that higher dietary intake of choline is associated with lower risk of pancreatic cancer, but no study has examined the association of serum choline and its metabolites with risk of pancreatic cancer. Two parallel case-control studies, one nested within the Shanghai Cohort Study (129 cases and 258 controls) and the other within the Singapore Chinese Health Study (58 cases and 104 controls), were conducted to evaluate the associations of baseline serum concentrations of choline, betaine, methionine, total methyl donors (i.e., sum of choline, betaine and methionine), dimethylglycine and trimethylamine N-oxide (TMAO) with pancreatic cancer risk. In the Shanghai cohort, odds ratios and 95% confidence intervals of pancreatic cancer for the highest quartile of choline, betaine, methionine, total methyl donors and TMAO were 0.27 (0.11-0.69), 0.57 (0.31-1.05), 0.50 (0.26-0.96), 0.37 (0.19-0.73) and 2.81 (1.37-5.76), respectively, compared to the lowest quartile. The corresponding figures in the Singapore cohort were 0.85 (0.23-3.17), 0.50 (0.17-1.45), 0.17 (0.04-0.68), 0.33 (0.10-1.16) and 1.42 (0.50-4.04). The inverse associations of methionine and total methyl donors including choline, betaine and methionine with pancreatic cancer risk in both cohorts support that DNA repair and methylation play an important role against the development of pancreatic cancer. In the Shanghai cohort, TMAO, a gut microbiota-derived metabolite of dietary phosphatidylcholine, may contribute to higher risk of pancreatic cancer, suggesting a modifying role of gut microbiota in the dietary choline-pancreatic cancer risk association.

Statins and pancreatic cancer risk in patients with chronic pancreatitis: A Danish nationwide population-based cohort study.

Statins (HMG-CoA reductase inhibitors) have antiinflammatory and possibly anticancer properties. We hypothesized that statin use is associated with lower risk of pancreatic cancer in patients with chronic pancreatitis. This nationwide population-based cohort study included all Danish patients diagnosed with incident chronic pancreatitis from 1 January 1996 to 31 December 2012. We used the Danish National Prescription Registry to ascertain information on statin prescriptions for members of the study population before and after their pancreatitis diagnosis. We computed crude incidence rates, incidence rate ratios (IRRs) and adjusted hazard ratios (HRs) with associated 95% confidence intervals (CIs) for pancreatic cancer, comparing statin users with nonusers. We computed HRs using Cox proportional hazards regression with statins treated as a time-varying exposure lagged by 1 year, adjusting for age, sex, socioeconomic status and individual comorbidities. The study included 8,311 chronic pancreatitis patients with a median age of 54 years. We observed 153 pancreatic cancers during 60,365 person-years of follow-up. The unadjusted IRR comparing statin users with nonusers was 1.00 (95% CI: 0.60-1.60). Adjustment for potential confounders only had a small impact on the estimate (adjusted HR: 0.90; 95% CI: 0.56-1.44). Our findings suggest that statin use is not associated with pancreatic cancer risk in patients with chronic pancreatitis.

Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.