Pancreatic cancer risk is modulated by inflammatory potential of diet and ABO genotype: a consortia-based evaluation and replication study

Abstract

Diets with high inflammatory potential are suspected to increase risk for pancreatic cancer (PC). Using pooled analyses, we examined whether this association applies to populations from different geographic regions and population subgroups with varying risks for PC, including variation in ABO blood type. Data from six case-control studies (cases, n = 2414; controls, n = 4528) in the Pancreatic Cancer Case-Control Consortium (PanC4) were analyzed, followed by replication in five nested case-control studies (cases, n = 1268; controls, n = 4215) from the Pancreatic Cancer Cohort Consortium (PanScan). Two polymorphisms in the ABO locus (rs505922 and rs8176746) were used to infer participants' blood types. Dietary questionnaire-derived nutrient/food intake was used to compute energy-adjusted dietary inflammatory index (E-DII®) scores to assess inflammatory potential of diet. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted logistic regression. Higher E-DII scores, reflecting greater inflammatory potential of diet, were associated with increased PC risk in PanC4 [ORQ5 versus Q1=2.20, 95% confidence interval (CI) = 1.85-2.61, Ptrend < 0.0001; ORcontinuous = 1.20, 95% CI = 1.17-1.24], and PanScan (ORQ5 versus Q1 = 1.23, 95% CI = 0.92-1.66, Ptrend = 0.008; ORcontinuous = 1.09, 95% CI = 1.02-1.15). As expected, genotype-derived non-O blood type was associated with increased PC risk in both the PanC4 and PanScan studies. Stratified analyses of associations between E-DII quintiles and PC by genotype-derived ABO blood type did not show interaction by blood type (Pinteraction = 0.10 in PanC4 and Pinteraction=0.13 in PanScan). The results show that consuming a pro-inflammatory diet and carrying non-O blood type are each individually, but not interactively, associated with increased PC risk.

Figure 1.

Non-O blood type is associated with increased pancreatic cancer risk compared with blood type O in the Pancreatic Cancer Case–Control (PanC4) studies, after adjusting for age (continuous), sex, race (White, other), personal history of diabetes (yes, no), family history of pancreatic cancer (yes, no), BMI (<25, 25-29, ≥30 kg/m², unknown), pack-years of smoking within smoking category (never, former with <15 pack-years, former with ≥15 pack-years, current with <15 pack-years, current with ≥15 pack-years), and with additional adjustment for study site (Mayo, MDACC, UCSF, Yale) in the pooled estimate. Genotype data were not available in the UMN and the Italian studies. Mayo, Mayo Clinic; MDACC, MD Anderson Cancer Center; UCSF, University of California at San Francisco; Yale, Yale University.

Figure 2.

Increased odds of pancreatic cancer risk among individuals with non-O blood type compared with those with blood type O in the Pancreatic Cancer Cohort Consortium (PanScan) studies, after adjusting for age (continuous), sex, race (White, other), personal history of diabetes (yes, no), family history of pancreatic cancer (yes, no), BMI (<25, 25–29, ≥30 kg/m², unknown), pack-years of smoking within smoking category (never, former with <15 pack-years, former with ≥15 pack-years, current with <15 packyears, current with ≥15 pack-years), and with additional adjustment for study site (ATBC, EPIC, PLCO, NYUWHS and SMWHS) in the pooled estimate. Analyses were restricted to individuals with genotype data. ATBC, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Trial; EPIC, European Prospective Investigation into Cancer and Nutrition; NYU-WHS, New York University Women's Health Study; PLCO, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial; SMWHS, Shanghai Men's and Women's Health Study.

Figure 3.

Every 1.87 units (i.e., standard deviation) increase in energy-adjusted dietary inflammatory index (DII) score (continuous variable) is associated with incremental risk of pancreatic cancer in each of the six Pancreatic Cancer Case–Control Consortium (PanC4) studies, in models that adjusted for age (continuous), sex, race (White, other), diabetes (yes, no), family history of pancreatic cancer (yes, no), BMI (< 25, 25-29, ≥30 kg/m², unknown), pack-years of smoking within smoking category (never, former with <15 pack-years, former with ≥15 pack-years, current with <15 pack-years, current with ≥15 pack-years) and with additional adjustment for study site (Mayo, UMN, MDACC, UCSF, Yale, and Italy) in the pooled estimate. Mayo, Mayo Clinic; MDACC, MD Anderson Cancer Center; UCSF, University of California at San Francisco; UMN, University of Minnesota; Yale, Yale University; Italy, Italian Case control Study.

Figure 4.

Association between every 1.72 units (i.e. standard deviation) increase in energy-adjusted dietary inflammatory index (DII) score (continuous variable) and pancreatic cancer risk among five Pancreatic Cancer Cohort Consortium (PanScan) studies, in models that adjusted for age (continuous), sex, race (White, other), diabetes (yes, no), family history of pancreatic cancer (yes, no), BMI (<25, 25–29, ≥30 kg/m², unknown), pack-years of smoking within smoking category (never, former with <15 pack-years, former with ≥15 pack-years, current with <15 pack-years, current with ≥15 pack-years) and with additional adjustment for study (ATBC, EPIC, PLCO, NYU-WHS and SMWHS) in the pooled estimate. ATBC, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Trial; EPIC, European Prospective Investigation into Cancer and Nutrition; NYU-WHS, New York University Women's Health Study; PLCO, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial; SMWHS, Shanghai Men's and Women's Health Study.