Bioinformatic and experimental methods were used to assess the distribution of MSR1 across the genome, evaluate the regulatory potential of such elements and explore the role of MSR1 elements in cancer, particularly non-familial breast cancer and prostate cancer.
Minor alleles of rs2243250 (T) in IL4 (OR = 1.46, 95% CI 1.03-2.08, P-trend = 0.03), rs1800896 (G) in IL10 (OR = 0.77, 95% CI 0.61-0.96, P-trend = 0.02), rs2430561 (A) in IFNG (OR = 1.33, 95% CI 1.02-1.74; P-trend = 0.04), rs3747531 (C) in MSR1 (OR = 0.55, 95% CI 0.32-0.95; P-trend = 0.03), and possibly rs4073 (A) in IL8 (OR = 0.81, 95% CI 0.64-1.01, P-trend = 0.06) were associated with higher- (Gleason 7-10; N = 222), but not lower- (Gleason 2-6; N = 380) grade prostate cancer.
In our study, we investigated the potential association between KLK3, AR, RNASEL, MSR1, and ELAC2 polymorphisms, expression patterns, exposure to environmental factors, and PCa in a Spanish cohort.
Our study provides the proof-of-principle that some of the genetic variants (such as rs486907, rs627928 and rs2127565) in genes RNASEL, MSR1 and ELAC2 can be used as predictors of aggressiveness and progression of PCa.
Many polymorphisms in genes, such as ELAC2 (locus HPC2), RNase L (locus hereditary prostate cancer 1 gene [HPC1]), and MSR1 have been recognized as important genetic factors that confer an increased risk of developing prostate cancer in many populations.
However, ionizing radiation combined with in situ vaccination with DCs, in which the immunosuppressive scavenger receptor A (SRA/CD204) has been downregulated by lentivirus-mediated gene silencing, profoundly suppressed the growth of two mouse prostate cancers (e.g., RM1 and TRAMP-C2) and prolonged the lifespan of tumor-bearing animals.
In this region, genetic variants of the class A scavenger receptor (SR-A) gene have been associated with prostate cancer risk and have been highlighted as a potential susceptibility gene of cancer.
Combining high-risk genotypes of MSR1 and ELAC2 in Caucasians and of RNASEL and MSR1 in Hispanics showed synergistic effects and suggest that an interaction between both genes in each ethnicity is likely to confer prostate cancer risk.
To evaluate further the relationship between MSR1 variants and prostate cancer risk, we sequenced all the 11 MSR1 exons, exon-intron junctions, promoter regions, as well as 5' and 3' untranslated regions (UTRs) in 86 individuals from Shanghai, China.
In analysis of selected candidate cancer susceptibility genes, two MSR1 SNPs (rs9325782, GEE p = 0.008 and rs2410373, FBAT p = 0.021) were associated with prostate cancer and three ERBB4 SNPs (rs905883 GEE p = 0.0002, rs7564590 GEE p = 0.003, rs7558615 GEE p = 0.0078) were associated with breast cancer.
Western blot showed that SRA protein was expressed at a higher level in PC-3 than in LNCaP cells, suggesting that SRA may be related to hormone-independent growth of prostate cancer.
Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment.
We examined polymorphisms within ELAC2 (S217L, A541T, E622V), MSR1 (P275A, R293X, aIVS5-59c), and RNASEL (E265X, R462Q, D541E) in 150 European-Americans with metastatic prostate cancer and 170 prostate cancer-free controls using pyrosequencing assays.
Overall, this meta-analysis suggests the MSR1 gene does not independently confer a major risk to PCa but may confer a moderate risk to PCa, especially in black men.