Association of Polygenetic Risk Scores Related to Cell Differentiation and Inflammation with Thyroid Cancer Risk and Genetic Interaction with Dietary Intake

SIMPLE SUMMARY: Global thyroid cancer incidence is increasing, especially in women. Genetic and environmental factors mutually contribute to its incidence. We aimed to identify genetic variants to influence thyroid cancer risk and determine their interactions with lifestyles in a large city hospital-based cohort (495 thyroid cancer patients and 56,439 control). The best polygenetic model included DIRC3_rs6759952, GAP43_rs13059137, NRG1_rs7834206, PROM1_rs72616195, LRP1B_rs1369535, and LOC100507065_rs11175834, tumorigenesis and cancer cell differentiation-related genes. Their high polygenetic risk scores (PRS) increased thyroid cancer risk by 3.90-fold compared to low-PRS. Thyroid cancer risk was elevated in females, high white blood cell counts, and high energy, low alcohol, and high seaweed intakes by 4.21, 4.03, 7.00, 4.11, and 4.02-fold, respectively. These factors interacted with PRS: the women with high-PRS elevated thyroid cancer risk much among women with high daily energy, seaweeds, and alcohol intake. These results could be applied to personalized nutrition plans to reduce thyroid cancer risk. ABSTRACT: The incidence of thyroid cancer continues to increase steadily, and this increasing incidence cannot be attributed solely to the overdiagnosis of microcarcinoma or technical advancements in detection methods and may also depend on environmental and genetic factors. However, the impacts and interactions of genetic and environmental factors remain controversial, and they may differ in Eastern and Western countries. The study’s purpose was to identify single nucleotide polymorphisms of genes related to cell differentiation and inflammation to influence thyroid cancer incidence and determine interactions with lifestyles in a large city hospital-based cohort. Genetic variants were selected by genome-wide association study with thyroid cancer participants (case; n = 495) and controls without cancers (n = 56,439). SNPs having gene–gene interactions were selected by generalized multifactor dimensionality reduction. Polygenic risk scores (PRSs) were generated by summing the number of selected SNP risk alleles. PRSs of the best model included 6 SNPs, that is, DIRC3_rs6759952, GAP43_rs13059137, NRG1_rs7834206, PROM1_rs72616195, LRP1B_rs1369535, and LOC100507065_rs11175834. Participants with a high-PRS had a higher thyroid cancer risk by 3.9-fold than those with a low-PRS. The following variables were related to an increased thyroid cancer risk; female (OR = 4.21), high white blood cell count (OR = 4.03), and high energy (OR = 7.00), low alcohol (OR = 4.11), and high seaweed (OR = 4.02) intakes. These variables also interacted with PRS to influence thyroid cancer risk. Meat/noodle diet patterns interacted with PRSs to increase thyroid cancer risk (p = 0.0023). In conclusion, women with a high-PRS associated with cell differentiation and inflammation were at an elevated thyroid cancer risk. Daily energy, seaweeds, and alcohol intake interacted with PRS for thyroid cancer risk. These results could be applied to personalized nutrition plans to reduce the risk of thyroid cancer.