Essay on Genetic Determinants of Prostate Cancer Among Men of African Descent

There are specific changes in epigenetics, and patterns on single-nucleotide-polymorphism amongst African men that are linked with the bigger threat of prostate cancer. There are also distinct variations in fusion-gene products. SEER data (2006) indicate that African-American men have high prevalence rates for prostate cancer (255.5 for every 100,000 people) as compared to other groups such as European Americans (161.4 for every 100,000 people). This is because of specific genetic factors dominant among Africans. Africans have candidate androgen metabolism genes that predispose them to the risk of contracting prostate cancer. First, increased androgens in the bloodstream have been a marker for higher susceptibility of populations to the risk of prostate cancer. African men are known to be one of the niche communities that have higher circulating levels of androgens (Zeigler-Johnson, Spangler, Jalloh, Gueye, Rennert & Rebbeck, 2008). The levels of dihydrotestosterone and related testosterone metabolites have a positive correlation with the risk of a population contracting prostate cancer.

Androgen ablation is also a critical marker in the prospects of reducing prostate tumor size and disease burden. Thus, the disposition of testosterone in a population is a significant marker of its perceived risk of contracting prostate cancer. This includes the enzymes that influence testosterone activation and inactivation. These enzymes affect the capability of testosterone metabolites to send signals. The critical genes are cytochromes p450 (CYP3A5, CYP3A4, and CYP3A43), and five alpha-reductase type II (SRD5A2). The gene pair CYP3A4*1B and CYP3A43*3 offer significant protective effects; and is more common amongst African Americans (35%) as compared to European Americans (4%)(Zeigler-Johnson, Spangler, Jalloh, Gueye, Rennert & Rebbeck, 2008).

The susceptibility genes for prostate cancer mentioned (CYP3A5, and SRD5A2) vary along racial lines. CYP3A4 is higher in African Americans than European Americans. The SRD5A2genotype has a V89L gene variant that has a prevalence of 30%, 27%, 19% and 18% amongst European Americans, African Americans, Ghanaians, and Senegalese.Other candidate genes that create susceptibility for prostate cancer include the macrophage scavenger receptor 1 (MSR1) (MIM 153622),2-5-oligoadenylate-dependent RNase L (RNASEL/HPC1) (MIM 180435) in addition to the ELAC2/HPC2 -17p (MIM 605367). RNASEL and MSR1 cause inflammation and innate immunity. Met1Ile and Glu265X are deleterious mutations most common amongst African Americans (Zeigler-Johnson, Spangler, Jalloh, Gueye, Rennert & Rebbeck, 2008).

2. Discuss the genetic determinants of breast cancer among Ashkenazi Jews (10 marks)

Breast cancer is caused by precise genetic components with the most widespread one being a genetic factor associated with the mutation of BRCA1 and BRCA2 gene. These genes are predisposed in every human, though some people have a genetic mutation that ends up causing a change in the genetic makeup for BRCA1 and BRCA2 (Brandt-Rauf, Raveis, Drummond, Conte & Rothman, 2006). Such mutations increase one's chance of contracting breast cancer. According to CDC (2016), about 50% of all women who contract mutation in their BRCA1 or BRCA2 gene face increased risk of contracting breast cancer at age 70.

Certain ethnic groups are known to have higher chances of contracting genetic mutation on their BRCA1 or BRCA2 genes. According to Brandt-Rauf, Raveis, Drummond, Conte, and Rothman (2006), one such group is the Ashkenazi Jews where 1 in every 40 women are known to have a mutation in their BRCA1 and BRCA2 genes. In the early years, the Ashkenazi Jews lived in closed communities in Europe, where their genetic defects were preserved and passed down their lineage. The isolation made the genetic mutations to flourish. The founder mutations on BRCA1 and BRCA2 genes are responsible for the high rate of breast cancer (1 in every 40 people) recorded amongst the Ashkenazi Jews in recent years. In comparison, the incidence rates for breast cancer in other non-Ashkenazi populations stand at 1 in every 800 people (Brandt-Rauf, Raveis, Drummond, Conte & Rothman, 2006).

References

Brandt-Rauf, S. I., Raveis, V. H., Drummond, N. F., Conte, J. A., & Rothman, S. M. (2006). Ashkenazi Jews and breast cancer: the consequences of linking ethnic identity to genetic disease. American Journal of Public Health, 96(11), 1979-1988.

Zeigler-Johnson, C. M., Spangler, E., Jalloh, M., Gueye, S. M., Rennert, H., &Rebbeck, T. R. (2008).Genetic susceptibility to prostate cancer in men of African descent: implications for global disparities in incidence and outcomes. The Canadian journal of urology, 15(1), 3872.