Prostate cancer is one of the most significant health concerns for men worldwide. Numerous researchers carrying out molecular diagnostics have indicated that genetic interactions with biological and behavioral factors play an important role in the overall risk and prognosis of this disease. Single nucleotide polymorphisms (SNPs) are increasingly becoming strong biomarker candidates to identify susceptibility to prostate cancer. We carried out a gene × environment interaction analysis linked to aggressive and non-aggressive prostate cancer (PCa) with a number of SNPs. By using this method, we identified the susceptible alleles in a New Zealand population, and examined the interaction with environmental factors. We have identified a number of SNPs that have risk associations both with and without environmental interaction. The results indicate that certain SNPs are associated with disease vulnerability based on behavioral factors. The list of genes with SNPs identified as being associated with the risk of PCa in a New Zealand population is provided in the graphical abstract.

Age is often considered an important non-modifiable risk factor for a number of diseases, including prostate cancer. Some prominent risk factors of prostate cancer include familial history, ethnicity and age. In this review, various genetic and physiological characteristics affected due to advancing age will be analysed and correlated with their direct effect on prostate cancer.

MED12, a subunit of mediator complex genes is known to harbor genetic mutations, (mostly in exon 2), causal to the genesis of uterine leiomyomas among Caucasian, African American, and Asian women. However, the precise relationship between genetic mutations vs. protein or disease phenotype is not well-explained. Therefore, we sought to replicate the MED12 mutation frequency in leiomyomas of Saudi Arabian women, who represents ethnically and culturally distinct population. We performed molecular screening of MED12 gene (in 308 chromosomes belonging to 154 uterine biopsies), analyzed the genotype-disease phenotype correlations and determined the biophysical characteristics of mutated protein through diverse computational approaches. We discovered that >44% (34/77) leiomyomas of Arab women carry a spectrum of MED12 mutations (30 missense, 1 splice site, and 3 indels). In addition to known codon 44, we observed novel somatic mutations in codons 36, 38, and 55. Most genetically mutated tumors (27/30; 90%) demonstrated only one type of genetic change, highlighting that even single allele change in MED12 can have profound impact in transforming the normal uterine myometrium to leiomyomas. An interesting inverse correlation between tumor size and LH is observed when tumor is positive to MED12 mutation (p < 0.05). Our computational investigations suggest that amino acid substitution mutations in exon-2 region of MED12 might contribute to potential alterations in phenotype as well as the stability of MED12 protein. Our study, being the first one from Arab world, confirms the previous findings that somatic MED12 mutations are critical to development and progression of uterine leiomyomas irrespective of the ethnic background. We recommend that mutation screening, particularly codon 44 of MED12 can assist in molecular diagnostics of uterine leiomyomas in majority of the patients.

Background: There is variable reporting on the benefits of a 200 μg/d selenium supplementation towards reducing prostate cancer impacts. The current analysis is to understand whether stratified groups receive supplementation benefits on prostate health. Methods: 572 men were supplemented with 200 µg/d selenium as selinized yeast for six months, and 481 completed the protocol. Selenium and prostate-specific antigen (PSA) levels were measured in serum at pre- and post-supplementation. Changes in selenium and PSA levels subsequent to supplementation were assessed with and without demographic, lifestyle, genetic and dietary stratifications. Results: The post-supplementation selenium (p = 0.002) and the gain in selenium (p < 0.0001) by supplementation were significantly dependent on the baseline selenium level. Overall, there was no significant correlation between changes in PSA and changes in selenium levels by supplementation. However, stratified analyses showed a significant inverse correlation between changes in PSA and changes in selenium in men below the median age (p = 0.048), never-smokers (p = 0.031), men carrying the GPX1 rs1050450 T allele (CT, p = 0.022 and TT, p = 0.011), dietary intakes above the recommended daily intake (RDI) for zinc (p < 0.05), and below the RDI for vitamin B12 (p < 0.001). Conclusions: The current analysis shows the influence of life factors on prostate health benefits of supplemental selenium.