The PDZ and LIM domain 5 (PDLIM5) gene may play a role in cancer, bipolar disorder, major depression, alcohol dependence and schizophrenia; however, little is known about the interaction effect of steroid and PDLIM5 gene on cancer. This study examined 47 single-nucleotide polymorphisms (SNPs) within the PDLIM5 gene in the Marshfield sample with 716 cancer patients (any diagnosed cancer, excluding minor skin cancer) and 2848 noncancer controls. Multiple logistic regression model in PLINK software was used to examine the association of each SNP with cancer. Bayesian logistic regression in PROC GENMOD in SAS statistical software, ver. 9.4 was used to detect gene–steroid interactions influencing cancer. Single marker analysis using PLINK identified 12 SNPs associated with cancer (P < 0.05); especially, SNP rs6532496 revealed the strongest association with cancer (P = 6.84 × 10−3); while the next best signal was rs951613 (P = 7.46 × 10−3). Classic logistic regression in PROC GENMOD showed that both rs6532496 and rs951613 revealed strong gene–steroid interaction effects (OR = 2.18, 95% CI = 1.31−3.63 with P = 2.9 × 10−3 for rs6532496 and OR = 2.07, 95% CI = 1.24 −3.45 with P = 5.43 × 10−3 for rs951613, respectively). Results from Bayesian logistic regression showed stronger interaction effects (OR = 2.26, 95% CI = 1.2 −3.38 for rs6532496 and OR = 2.14, 95% CI = 1.14 −3.2 for rs951613, respectively). All the 12 SNPs associated with cancer revealed significant gene–steroid interaction effects (P < 0.05); whereas 13 SNPs showed gene–steroid interaction effects without main effect on cancer. SNP rs4634230 revealed the strongest gene–steroid interaction effect (OR = 2.49, 95% CI = 1.5 −4.13 with P = 4.0 × 10−4 based on the classic logistic regression and OR = 2.59, 95% CI = 1.4 −3.97 from Bayesian logistic regression; respectively). This study provides evidence of common genetic variants within the PDLIM5 gene and interactions between PLDIM5 gene polymorphisms and steroid use influencing cancer.

The PDZ and LIM domain 5 (PDLIM5) gene may play a role in alcohol dependence (AD), bipolar disorder, and major depressive disorder; however, no study has identified shared genetic variants within PDLIM5 gene among AD, type 2 diabetes (T2D), and hypertension. This study investigated the association of 72 single nucleotide polymorphism (SNPs) with AD (1066 AD cases and 1278 controls) in the Study of Addiction - Genetics and Environment (SAGE) sample and 47 SNPs with T2D (878 cases and 2686 non-diabetic) and hypertension (825 cases and 2739 non-hypertensive) in the Marshfield sample. Multiple logistic regression models in PLINK software were used to examine the associations of genetic variants with AD, T2D, and hypertension and SNP x alcohol consumption interactions for T2D and hypertension. Twenty-five SNPs were associated with AD in the SAGE sample (p < 0.05); rs1048627 showed the strongest association with AD (p = 5.53 × 10−4). Of the 25 SNPs, 5 SNPs showed associations with both AD in the SAGE sample and T2D in the Marshfield sample (top SNP rs11097432 with p = 0.00107 for T2D and p = 0.0483 for AD) while 6 SNPs showed associations with both AD in the SAGE sample and hypertension in the Marshfield sample (top SNP rs12500426 with p = 0.0119 for hypertension and p = 1.51 × 10−3 for AD). SNP (rs6532496) showed significant interaction with alcohol consumption for hypertension. Our results showed that several genetic variants in PDLIM5 gene influence AD, T2D and hypertension. These findings offer the potential for new insights into the pathogenesis of AD, T2D, and hypertension.