Dietary Vitamin K Intake and the Risk of Pancreatic Cancer

A Prospective Study of 101,695 American Adults

Dao-Wu Yu; Qu-Jin Li; Long Cheng; Peng-Fei Yang; Wei-Ping Sun; Yang Peng; Jie-Jun Hu; Jing-Jing Wu; Jian-Ping Gong; Guo-Chao Zhong

Disclosures

Am J Epidemiol. 2021;190(10):2029-2041. 

In This Article

Results

Participant Characteristics

In the whole study population, the mean energy-adjusted dietary intakes of phylloquinone, menaquinones, and dihydrophylloquinone were 146.2 (standard deviation (SD),155.7) μg/day, 11.7 (SD, 13.7) μg/day, and 3.9 (SD, 3.5) μg/day, respectively. Table 1 shows baseline characteristics of the study population by quartile of energy-adjusted dietary vitamin K intake. Individuals in the highest versus the lowest quartiles of dietary phylloquinone intake had higher physical activity levels and Healthy Eating Index-2015 scores and were more likely to take single or multivitamin supplements.

Compared with individuals in the lowest quartile of dietary menaquinone intake, those in the highest quartile were more likely to be male and current or former smokers, had higher alcohol consumption but lower Healthy Eating Index-2015 scores, and were more likely to have a history of diabetes but less likely to use single or multivitamin supplements. When the study population was categorized by dietary dihydrophylloquinone intake, similar trends were observed. In addition, individuals in the highest versus the lowest quartiles of dietary intake of phylloquinone, menaquinones, or dihydrophylloquinone had higher energy intake from diet and higher intakes of vegetables, meat, coffee, dairy, fiber, saturated fatty acids, polyunsaturated fatty acids, calcium, magnesium, folate, and vitamin A.

Dietary Vitamin K Intake and the Risk of Pancreatic Cancer

A total of 361 pancreatic cancer cases were documented during a mean follow-up of 8.86 (SD, 1.91) years (900,744.57 person-years). The overall incidence rate of pancreatic cancer in our study population was 4.01 cases per 10,000 person-years. Table 2 shows the results of Cox regression on the association of dietary vitamin K intake with the risk of pancreatic cancer in the whole study population. In the fully adjusted model (model 3), individuals in the highest quartile of dietary phylloquinone intake had a lower risk of pancreatic cancer than did those in the lowest quartile (for quartile 4 vs. quartile 1, HR = 0.57, 95% confidence interval (CI): 0.39, 0.83; P for trend = 0.002). Similarly, compared with persons in the lowest quartile, those in the highest quartiles of dietary dihydrophylloquinone intake were found to have a lower risk of pancreatic cancer (for quartile 4 vs. quartile 1, HR = 0.59, 95% CI: 0.41, 0.85; P for trend = 0.006). However, no significant association with the risk of pancreatic cancer was observed for dietary menaquinone intake (for quartile 4 vs. quartile 1, HR = 0.93, 95% CI: 0.65, 1.33; P for trend = 0.816). When the above-mentioned analyses were repeated in 72,903 individuals for whom we had complete data, the direction and the magnitude of the association between dietary vitamin K intake and the risk of pancreatic cancer did not alter substantially, although the linear trend was found to be nonsignificant for dietary dihydrophylloquinone intake (P for trend = 0.426) (Web Table 3).

Additional Analyses

Using restricted cubic spline functions, we found that dietary intakes of phylloquinone (P for nonlinearity = 0.001) and dihydrophylloquinone (P for nonlinearity = 0.008) were inversely related to the risk of pancreatic cancer in a nonlinear dose–response pattern, whereas such a relationship was not found for dietary menaquinone intake (P for nonlinearity = 0.197) (Figure 3). The initial association of dietary intakes of phylloquinone, menaquinones, and dihydrophylloquinone with the risk of pancreatic cancer was not modified by age, sex, BMI, single or multivitamin supplement use, aspirin use, smoking status, and Healthy Eating Index-2015 score in subgroup analyses (all P for interaction > 0.05) (Web Table 4) and did not change materially in a large range of sensitivity analyses (Web Table 5).

Figure 3.

Dose–response analyses on the association of dietary intakes of A) phylloquinone, B) menaquinones, and C) dihydrophylloquinone with the risk of pancreatic cancer, , the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 1993–2009. The reference levels were set as 53.0 μg/day, 3.4 μg/day, and 1.0 μg/day for dietary intakes of phylloquinone, menaquinones, and dihydrophylloquinone, respectively. Hazard ratios were adjusted for age, sex, smoking status, alcohol consumption, physical activity level, body mass index, aspirin use, history of diabetes, family history of pancreatic cancer, intakes of dietary fiber and folate, and energy intake from diet. P values for nonlinearity were 0.001 for phylloquinone intake, 0.197 for menaquinone intake, and 0.008 dihydrophylloquinone intake. CI, confidence interval.

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