The Association Between the Genetic VDR SNP c.907+75C>T and Prostate Cancer Risk Is Modified by Tanning Potential.

BACKGROUND: Prostate cancer (PCa) is a multifactorial disease involving complex interactions between genetic and physiological/environmental factors. Vitamin D receptor (VDR) plays a role in numerous cellular pathways and it has been suggested that VDR genetic variants influence individual susceptibility to PCa. MATERIALS AND METHODS: Logistic regression analysis was used to assess the association of six VDR single nucleotide polymorphisms (SNPs) and factors such as tanning potential and UV sunlight exposure with PCa risk. RESULTS: Marginal significant interactions were found, with a 2-fold increase risk of PCa between SNP 1 (c.278-69G>A) and sunlight UV exposure [odds ratio (OR)=2.02, 95% confidence intervaI (CI)=1.036-4.36; p=0.05]; and a 4-fold increase risk of PCa between SNP 4 (c.907+75C>T) and tanning potential (OR=4.40, 95% CI=0.89-29.12; p=0.0591). In contrast, SNP 5 (rs731236, TaqI) and tanning potential interaction had a protective effect by reducing the risk of PCa by 55% (ß=-0.804; OR=0.448, 95% CI=0.197-9.42; p=0.0427). SNPs 2 (rs61614328) and 6 (rs533037428) did not show any association with PCa even in the presence of UV sunlight exposure. CONCLUSION: The protective effect of SNP 4 from PCa is lost and modified by tanning potential in African Americans. This finding needs to be verified by larger studies in different ethnic populations.

Corrigendum to "Annexin 2 protein expression is associated with breast cancer subtypes in African American women" [Heliyon Volume 6, Issue 2, February 2020, e03241].

[This corrects the article DOI: 10.1016/j.heliyon.2020.e03241.].

Annexin 2 protein expression is associated with breast cancer subtypes in African American women.

BACKGROUND: A review of literature on the expression of Annexin 2 in cancer has shown that there is very limited research work on the association of this protein with breast cancer aggressiveness in African Americans. In the present study, TMA breast tissues from African American women were stained with Annexin 2 antibody to determine the association between the molecular subtypes and Annexin 2 protein expression. METHOD: An annotated case series of 135 breast cancer tissues archived from 2000 to 2010 was acquired from the Howard University Tumor Registry. The association between ANX2 expression and survival by molecular subtypes Luminal A, Luminal B, HER2, and Triple Negative (TN) was assessed using Multinomial regression, chi-square analysis, and Kaplan-Meir graphs (Stata 11). RESULTS: Our findings show a marked association between ANX2 protein expression in Luminal B and HER2 subtypes unadjusted and when adjusted for age. Borderline differences in tumor grade were found in TN only.Univariately, age (<50, 50 + years) and metastases were highly significant for overall survival, disease-free survival and recurrence-free survival. Stage, tumor size, and nodal involvement were of borderline or greater significance for overall and disease-free survival. ANX2 expression was not significant. Kaplan Meier tests of ANX2 showed significant separation of overall survival by ANX2 protein expression in all breast tumor subtypes. In multivariate analyses comparing TN to Luminal A, ANX2 was not important while controlling for age and grade. CONCLUSION: ANX2 might be a biomarker of aggressiveness and a relevant candidate biomarker in high risk African American women with Luminal B and HER2 breast cancer.

Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men.

BACKGROUND: Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa. METHOD: We investigated protein expression of Annexin 2 (ANX2), serine peptidase inhibitor, kazal type 1(SPINK1)/tumor-associated trypsin inhibitor (TATI), and heat shock protein 60 (Hsp60) in 79 archival human prostate trans-rectal ultrasound (TRUS) biopsy tissues according to a modified World Health Organization (WHO) classification: normal (WHO1a), Gleason Score (GS6 (WHO1b), GS7 subgroups (WHO2 = 3 + 4, WHO3 = 4 + 3), GS8 (WHO4), and GS9-10 (WHO5). AA men aged 41-90 diagnosed from 1990 to 2013 at Howard University were included. Automated staining assessed expression of each biomarker. Spearman correlation assessed the direction and relationship between biomarkers, WHO and modified WHO GS, age, and 5-year survival. A two-tailed t-test and ANOVA evaluated biomarkers expression in relationship to WHO normal and other GS levels, and between WHO GS levels. A logistic and linear regression analysis examined the relationship between biomarker score and WHO GS categories. Kaplan-Meier curves graphed survival. RESULTS: ANX2 expression decreased monotonically with the progression of PCa while expression of SPINK1/TATI and Hsp60 increased but had a more WHO GS-specific effect; SPINK1/TATI differed between normal and GS 2-6 and HSP60 differed between GS 7 and GS 2-6. WHO GS was found to be significantly and negatively associated with ANX2, and positively with SPINK1/TATI and Hsp60 expression. High SPINK1/TATI expression together with the low ANX2 expression at higher GS exhibited a bi-directional relationship that is associated with PCa progression and survival. CONCLUSION: Importantly, the data reveal that ANX2, and SPINK1/TAT1 highly associate with WHO GS and with the transition from one stage of PrCa to the next in AA men. Future research is needed in biracial and larger population studies to confirm this dynamic relationship between ANX2 and SPINK1 as independent predictors of PCa progression in all men.