Genes associated with prostate cancer.
Genetic polymorphism and prostate cancer (PC) are the most pernicious and recurrently malignancy worldwide. It is the most dominating cause of cancer related casualty among men in the US. Asian countries are inflicted with PC at an alarming rate though still the prevalence of PC is lower than European and American men. Some of the genetic and environmental factors that might play a role in PC risk include: age genetic predilection, family history, race/ethnicity, lifestyle, and dietary habits and non-dietary environmental risk factors such as smoking. Socio-economic factors including economic, scholastic and intellectual factors do not, intrinsically seem to straight away influence the risk of acquiring PC. Other genetic changes that may support an increased risk of developing PC include HPC1, HPC2, HPCX, CAPB, ATM,s HOXB13 and mismatch repair genes. PC occurrence rates are highly variable. Almost all PC mortalities are due to metastatic disease, generally through tumors the progress to be hormone refractory or castrate resistant. PC, developing research has acknowledged a number of candidate genes and biological pathways associated with PC. Indirect pathways such as P13K/AKT signaling pathway is one of most well known alternate pathway in PC Vascular endothelial growth factor (VEGF) is widely known to be potent stimulator of angiogenesis. The over expression of EGFR in a very large majority of cases is accompanied by the succession of PC, implying that this may play a mechanistic role. Numerous occupational factors have been proposed to cause PC. Some of the risk factors include; farmers/agricultural workers, pesticides, shift work and flight personnel. PC treatment can be done through surgery, radical prostatectomy is the main type of surgery. Risks of injury are many – reactions to anesthesia, loss of blood, blood clumps in the legs/lungs, injury to surrounding organs, infection at the site of surgery and many more. The other treatments are hormone therapy, chemotherapy and radio therapy chemotherapy. Chemotherapeutic drugs are typically used one at a time for PC such as transurethral resection of prostate (TURP). Some of the chemotherapeutic drugs are Docetaxel, Cabazitaxel, Mitoxantrone and Estramustine. Among the score of biomarkers being studied, numerous markers and techniques deserve awareness and acceptability for both patients and urologists in clinical practice.
- P13K/AKT signaling pathway
- single nucleotide polymorphisms (SNPs)
Cancer is both genetically and phenotypically sophisticated. Among all the cancers known so far, prostate cancer (PC) is the most pernicious and recurrently diagnosed malignancy worldwide (after lung cancer), counting 1,414,259 new cases (7.3% of all cancer associated diseases) and causing 375,304 deaths (3.8% of all deaths caused by cancer in men) in 2020 . It is the second most dominating cause of cancer related casualty among men in the United States. Prostate cancer is expected to cause 248,530 new cases and 34,130 deaths in the United States in 2021, making it the most common cancer among American men . Prostate cancer is thought to contain a genetic makeup that includes somatic copy number changes, point modifications, structural rearrangements, and chromosomal number differences . The somatic transformation rate of prostate cancer lies between 1x10−6 and 2x10−6 which is identical to breast, renal and ovarian cancer . However, in addition to somatic genetic alterations, it has been discovered that prostate cancer is associated with the loss of tumor suppressor gene activity due to epigenetic changes in their expression. Prostatic adenocarcinoma is the most frequent type of prostate cancer, accounting for nearly all occurrences. It grows in the cells of the glands that produce prostatic fluid. A digital rectal exam (DRE), a prostate-specific antigen (PSA) blood test, a prostate biopsy, or a computed tomography (CT) scan are all common ways for a clinician to detect prostate cancer .
Prostate cancer is categorized as the third highest among cancers of the male urinary and reproductive system in China. In Chinese populations, this condition impairs the quality of life and longevity of men over the age of 50 . India presently has a population of over a billion people, with an estimated 1.5 million cancer cases reported each year. Asian Indians were diagnosed at an average age of 65.9 years (range: 46–86 years). India has a low incidence of prostate cancer. However, due to a dearth of prostate cancer screening, the majority of individuals are detected at an advanced stage . The percentage of individuals with late-stage prostate cancer who have both high-grade illness and bone metastases is 65 percent. African-American men had a greater occurrence rate and a more severe kind of prostate cancer than White men. Prostate cancer is currently afflicting Asian countries at an alarming rate. Still, the prevalence of prostate cancer in Asian men is comparatively lower than European and American men. One reason that is endorsed by epidemiologic studies of immigrant populations and by recent somatic genomic alteration analysis is due to distinct genetic backgrounds. The etiological factors correlated with prostate cancer are still unresolved and ambiguous . Variations in social, environmental, and genetic factors are thought to be the cause of this disparity. Some of the factors that may influence the risk of prostate cancer include:
Age, genetic predisposition,
lifestyle and food habits are all factors to consider.
Although hereditary factors have been suspected to have a role in prostate cancer etiology, only a few genetic markers linked to prostate cancer risk have been identified. The strongest risk factor is acknowledged to be a hereditary liability . Variations in the usage of diagnostic tests are reflected in the incidence rates around the world. The importance of family history in obtaining evidence for major genetic determinants in cancer prevalence cannot be overstated. Prostate cancer progression and progression are influenced by lifestyle and nutritional habits. Future research is needed to better understand the interaction of environmental and diaspora factors . Prostate cancer is generally asymptomatic at the initial stage and may require minimal or no treatment at all. However, the most recurring grievance is complications with urination and nocturia. Prostatic hypertrophy causes all of the symptoms listed above. Because the axial skeleton is the most prevalent site of bone metastatic disease, more advanced stages of the disease may exist with urine retention and back pain .
Genetics has an important role in the initiation and progression of prostate cancer. Tumor biomarkers are used to detect, treat, and diagnose many tumors in their early stages. Understanding the genesis and causative risk factors for prostate cancer can help to provide some solutions. This can aid in the expansion of significant screening and precluding methods for prostate cancer. Currently, no evidence supports how to prevent this cancer . A promising understanding of the etiology and causative risk components is crucial for understanding cancer prevention. This cancer has a complex, multiple etiology, with 42 percent genetic factors and 58 percent environmental/lifestyle factors estimated to be involved. Prostate cancer is a growing threat to Asian men’s health. Although the rate of incidence of prostate cancer is far greater in Western cultures (120 per 100,000 in Northern America) than in East Asian cultures (less than 10 per 100,000 in Asia), when Asians migrate to Western countries, their rate of prostate cancer incidence increases . Prostate cancer has all of the criteria of an excellent chemoprevention target illness, including a lengthy latency, high incidence, a huge proportion of tumor markers, and identifiable preneoplastic lesions.
The increased morbidity and mortality from prostate cancer necessitate the implementation of current and effective preventive measures in everyday life. In conclusion, no vital known lifestyle or infectious agent is recognized as a risk factor for prostate cancer, categorizing it as one of the limited widespread cancers with unidentified risk factor .
2. Occurrence rates
Prostate cancer occurrence rates are highly variable. Occurrence, stringency, and mortality rates vary with ethnicities, geological location, and age. Its risk increases with an increase in age with the youngest being least susceptible. Also, this cancer is more widespread and invasive in African-Americans . Native Asians, on the other hand, have a remarkably low incidence of prostate cancer, which is likely due to a combination of environmental and hereditary factors. Prostate cancer has the highest occurrence of 83.4% per 1000,000 incidences in Northern Europe, notably Ireland, and the lowest occurrence rate in South Central Asia, at 6.3 per 100,000. In Asia, however, prostate cancer accounts for only 1–10% of cases, but the incidence of occurrence is rapidly increasing .
Prostate cancer ranks second (37.5 per 100,000) in nations with a high Human Development Index (HDI), and vice versa in countries with a low HDI (11.3 per 100,000). The highest occurrence rates of prostate cancer are found among black men in the United States and the Caribbean, confirming the importance of Western African ancestry in controlling prostate cancer risk. The variation in prostate cancer incidence rates is mainly due to different prostate cancer diagnostic practices globally. In the early 1980s and late 1990s, there was a drastic increase in prostate cancer cases in the United States, Australia, and Canada due to which the detection of pre-symptomatic cancer was feasible . The adoption of prostate-specific antigen (PSA) testing was a major factor in this. One of the most striking features of prostate cancer is the wide range of occurrence rates caused by differences in race, geography, or age, as well as variations in environmental factors such as work environment, nutrition, and lifestyle, all of which can increase the risk of precocious prostate cancer. Environmental factors are one of the reasons for varied incidence rates of different cancers globally . The cause of prostate cancer is unknown, even though it is more common in some populations. However, it is clear that prostate cancer is a multifaceted illness with various genetic and environmental variables contributing to its etiology.
3. Mortality rates
Almost all deaths from prostate cancer are caused by metastatic illness, which occurs when tumors become hormone-refractory or castrate-resistant. Prostate cancer mortality rates have dropped dramatically in Northern America, Northern, and Western Europe, indicating improved treatment and early detection through increased screening . The highest mortality rate of prostate cancer is 27.9 per 100,000 in the Caribbean, with the lowest mortality rate being 3.1 per 100,000 in South Central Asia. The highest occurrence and mortality rates are found in African-American men. As a result, we can speculate that African-American males may maintain some genes that are more susceptible to mutations in prostate cancer and that these mutations are linked to a more aggressive type of cancer. African-American men, as well as men with a family history, should be screened at the age of 45. Undeniable death is the most important prostate cancer endpoint .
4. Genes associated with prostate cancer risk
Developing research has acknowledged a number of candidate genes and biological pathways associated with increased susceptibility to cancer. A significantly recent direction for scientists to identify genes involved in human disease is Genome-wide association studies (GWAS) . This approach looks for tiny differences in the genome known as SNPs (single-nucleotide polymorphisms). Because genome-wide association studies examine SNPs across the genome, they promise a promising technique to research complex, prevalent diseases in which numerous genetic variations contribute to a person’s risk. Genome-wide association studies provide an enormous approach for the identification of genetic markers correlated with prostate cancer risk. Hundreds of thousands of SNPs can be examined simultaneously in each analysis . In genome-wide association studies (GWAS), case–control surveys, multiple linkage estimations, next-generation sequencing (NGS), and admixture mapping studies, several genes and chromosomal areas have been identified to be associated with prostate cancer. As more prostate cancer risk variations are identified, the cumulative effects of these variants may become increasingly important clinically. Unfortunately, attempts at specifying a reliable biomarker have thus far proved futile (Table 1) [15, 16, 17].
|Genes||Population||N (Total Cases Studied)||Prostate cancer risk||Reference|
|UK and IRELAND||376||Weakly validated||Nyberg et al., 2020|
|UK and IRELAND||447||Validated||Nyberg et al., 2020|
|NON-HISPANIC WHITE||226||Validated||Ingles et al., 1997|
|NORTHERN EUROPEAN||3508||Validated||Cooney et al., 2016|
|TUNISIAN||250||Validated||Souiden et al., 2011|
|CHINESE||495||Validated||Hsing et al., 2001|
|398||Validated||Singh et al., 2013|
|EUROPEAN AMERICANS, JAPANESE and AFRICAN AMERICANS||483||Validated||Grisanzio et al., 2012|
|SOUTHERN CHINESE HAN||509||Validated||Xu et al., 2010|
|EUROPEAN||19421||Validated||Prokunina-Olsson et al., 2010|
|CAUCASIAN||1859||Validated||Nicolaiew et al., 2009|
|(||SWEDISH||2425||Not validated||Wiklund et al., 2004|
|AUSTRALIAN||1557||Not validated||Severi et al., 2003|
|CHINESE||410||Validated||Hsing et al., 2007|
|JAPANESE||782||Not validated||Wang et al., 2003|
|ASHKENAZI JEWISH||2230||Validated||Agalliu et al., 2010|
There is a significant role of genetics in prostate cancer that is indicated through epidemiological studies. In the advancement and succession of prostate cancer, there is an involvement of a heightening number of single nucleotide polymorphisms (SNPs). Individual SNPs show a moderate connection with prostate cancer risk, but when they are combined, they have a larger, dose-dependent association that presently accounts for 30% of prostate cancer family risk. An SNP is a deviation from the predicted nucleotide in a DNA sequence that arises when a single nucleotide (A, T, C, or G) in the genome changes [20, 21, 22, 23, 24]. SNPs are thought to make a significant impact on disease vulnerability. SNPs are simple to find and only exist once, making them an ideal biomarker. Because of the growing interest in the role of SNPs in prostate cancer progression and succession, a large number of studies on SNPs in prostate cancer are being published .
Many case–control studies have recognized innumerable single nucleotide polymorphisms (SNPs) correlated with prostate cancer but the clinical role of these SNPs remains ambiguous. Some SNPs also affect levels of the prostate-secreted proteins, prostate-specific antigen (PSA), hexokinase (HK) 2, and β-microseminoprotein (β-MSP); prostate cancer risk was also related with some of these SNPs. Numerous SNPs associated with prostate cancer affect the role and/or generation of a prostate cancer marker. For example, rs198977 in
|SNP||Chromosome||Population||N (Total Cases Studied)||Prostate Cancer Risk||Reference|
|rs6983267||8q24||Caucasians and Asians||50854||Identified||Li et al., 2015|
|rs1447295||8q24||Caucasians and Asians||50854||Identified||Li et al., 2015|
|rs16901979||8q24||Africans Americans||50854||Identified||Li et al., 2015|
|rs138213197||HOXB13||Europeans||9012||Identified||Beebe-Dimmer et al., 2015|
|rs4242382||8q24||Asian and Caucasian||3657||Identified||Zhao et al., 2014|
|rs4430796||17q12||Non-Hispanic White||421||Identified||Levin et al., 2008|
|rs7501939||17q12||Non-Hispanic white||421||Identified||Levin et al., 2008|
|rs10896449||11q13||European||19395||Identified||Chung et al., 2011|
|rs10486567||7p15.2||Finnish||947||Not identified||Chen et al., 2014|
|rs1938781||11q12||Japanese||5560||Identified||Akamatsu et al., 2012|
|rs2252004||10q26||Japanese||5560||Identified||Akamatsu et al., 2012|
|rs2055109||3p11.2||Japanese||5560||Identified||Akamatsu et al., 2012|
|rs1859962||17q24||Non-Hispanic white||421||Not Identified||Levin et al., 2008|
|rs12793759||11q13||European||19395||Identified||Chung et al., 2011|
|rs3737559||2p15||Icelander||23205||Identified||Gudmundsson et al., 2008|
|rs5945572||Xp11.22||Icelander||23205||Identified||Gudmundsson et al., 2008|
The t-allele of
Androgens are widely known to play a significant role in the progression of prostate cancer, even until it reaches advanced stages. In prostate cancer, especially castration-resistant prostate cancer, the androgen receptor (AR) plays a critical role (CRPC) . Androgen deprivation therapy suppresses hormone-naive prostate cancer; however, AR is altered by prostate cancer and adapts for survival at castration levels of androgen. The AR gene can be found on chromosome X (Xq11–12). Shorter glutamine repeats have been linked to increased AR transcriptional activity . The role of epithelial AR is to send secretory proteins to the prostate gland, such as prostate-specific antigen (PSA), whereas stromal AR is involved in prostate development. Most prostate cancers can be suppressed with androgen deprivation therapy, however, some high-risk prostate tumors progress to castration-resistant prostate cancer, which then thrives under castrated testosterone levels . AR is the most frequent anomalous gene in metastatic CRPC. Several mechanisms play a fundamental role in the development of metastatic CRPC: Point mutations in the androgen receptor, Androgen receptor amplification, Variations of androgen biosynthesis, Variations in androgen receptor cofactor in the prostate cancer, and Androgen receptor variants .
The binding of anti-androgens such as bicalutamide and flutamide to the ligand-binding domain (LBD) of AR inhibits androgen binding to LBD. In the progression of prostate cancer to castration-resistant prostate cancer, prostate cancer survives and restarts its growth under castration levels of androgen. A second-generation non-steroidal anti-androgen with greater affinity for the LBD of AR is Enzalutamide . Androgens play a critical role in the progression of both normal prostate epithelium and stromal prostate cancer, and activation of genes involved in androgen metabolism may be linked to an increased prostate cancer risk.
A fundamental regulatory enzyme in the steroidogenic pathway is Cytochrome P450 17α-hydroxylase/17,20-lyase (
In the breast cancer predisposition gene 2 (
Hereditary prostate cancer 1 gene (
5. Alternate pathways of PC risk
5.1 PI3K/Akt signaling pathway
Further, there is an involvement of the
Although present research suggests that this pathway gives predictive information, it is unclear whether it offers many significant advantages over currently employed clinical and pathologic indicators. However, there is continued interest in using this pathway as a predictive biomarker for newly targeted medicines of this pathway. Activation of the
5.2 Vascular endothelial growth factor (VEGF)
In both healthy and pathological settings, vascular endothelial growth factor (
5.3 Epidermal growth factor receptor (EGFR)
The overexpression of
5.4 Single nucleotide polymorphisms (SNPs)
In addition, GWAS has identified more than 150 SNVs related to the advancement of prostate cancer, but the clinical advantage of these findings remains skeptical.
Gudmundsson and colleagues identified two prostate cancer susceptibility loci on chromosome 17q in a recent genome-wide association study. Precisely, there was an association of two intronic SNPs in the
The prostate cancer susceptibility alleles on chromosome
Chen et al. demonstrated that two loci (rs4242382 and rs10486567) are highly associated with familial multiple prostate cancer. A stronger effect of the risk allele A at rs10486567 was observed in the presence of the risk allele A at rs4242382. The SNP rs10486567 at 7p15.2 was consistent with the genome-wide study. A three C2-H2-type zinc finger protein, which is a transcriptional repressor of
11q12, 10q26and 3p11.2
We have identified three new loci, 11q12, 10q26, and 3p11.2, that are associated with prostate cancer susceptibility at a genome-wide significance level in the Japanese population. These findings provide additional support for conducting GWAS for prostate cancer in diverse populations to identify risk loci for this genetically heterogeneous cancer. Akamatsu et al. showed that there are three new loci, 11q12, 10q26, and 3p11.2 that are associated with prostate cancer vulnerability at a genome-wide significance level in the Japanese population. These findings provide additional assistance for conducting Genome-wide association studies for prostate cancer in diverse populations to recognize risk loci for this genetically heterogeneous cancer. Further functional studies are required to understand the biological consequences of the newly recognized vulnerable loci in prostate cancer carcinogenesis .
For SNP rs5945572 A on
A risk factor is anything that increases a person’s chance of developing cancer. Although risk factors often influence the chance to develop cancer, most of them do not directly or by themselves cause cancer. Some people with several known risk factors never develop cancer, while others with no known risk factors do . In prostate cancer, it is normal to distinguish between epidemiologic endogenic factors (e.g., race, hormonal factors, genealogical information, age, etc.) and exogenic factors (e.g., sustenance, ecological factors, and lifestyle) which also include smoking, excess body fat accumulation.
6. Genetic and environmental risk factors
One of the most important risk factors for prostate cancer is age. Between the ages of 55 and 74, a person’s risk of acquiring prostate cancer is estimated to be. The occurrence and mortality rates of prostate cancer are significantly linked to age, with the highest prevalence found in older men over 65 years of age .
African-Americans have the highest prostate cancer risk, followed by whites, Hispanics, American Indians/Alaska Natives, and Asian/Pacific Islanders. According to the American Cancer Society, African-Americans have a death rate that is double that of white men. The risk of prostate cancer in Scandinavian males may also be higher. Historically, the occurrence rate in East Asia (Japan and China) has been low. However, when Chinese and Japanese men immigrate to the U.S., they have an elevated risk of developing prostate cancer when compared with their native populations .
The high intake of calories and fats in western diets is undoubtedly one of the primary causes of prostate cancer. Saturated fat, which is often ingested from animal sources, may be linked to the development of prostate cancer, however the link is small. Red meat is a key component of animal-fat consumption, and some research suggests red meat consumption has risk ratios. The biological causes for this link are still a mystery. Alpha-linolenic acid, an 18-carbon fatty acid found in meat and some vegetable oils, is significant because it is a necessary precursor for the creation of prostaglandins and leukotrienes. More research is needed to see if dietary substitution of fatty acids implicated in the prostaglandin production pathways affects prostate cancer development .
There are more than 20 epidemiological studies that have evaluated the role of dairy food intake in prostate cancer. These studies are compatible with a positive association, unrelated to the contribution of dairy foods to total and saturated fat intake. Although β-carotene intake has not been related with prostate cancer risk, another crucial dietary carotenoid compound—lycopene—has become the priority of considerable notoriety. Lycopene, which is mostly absorbed through the ingestion of tomato-based foods, is the most important carotenoid in most Americans’ diets. Consuming either a lycopene-rich diet or a β-carotene additive is thought to reduce the incidence of prostate cancer by about 40% . Legumes, which include but are not limited to soy, have also been researched concerning to prostate cancer risk. So far, nothing has been corroborated by the findings. Green tea, another plant product that includes several polyphenolic chemicals with possible anti-carcinogenic qualities, is also being investigated.
Obesity has been found to not affect the overall risk of prostate cancer, according to numerous studies. Obese men, on the other hand, are more likely to develop more aggressive forms of prostate cancer.
6.5 Family history
Numerous investigations, including familial prostate cancer gatherings, twin studies, and illness incidence in young individuals, support the importance of genetic variables. Prostate cancer is classified into two types: familial and sporadic. Familial/genealogical prostatic disease is a malignancy that occurs in affected members of one family at an early age (55 years old). This type of cancer has at least one first-degree relative with prostate cancer [48, 49, 50, 51, 52, 53]. However, in sporadic prostate cancer, the genetic material is damaged over time due to external environmental sensitivity. A family can be affected by this type of cancer if three generations are affected, three first-degree relatives are affected, or two relatives are affected before the age of 55. Both forms of cancer have different rates of occurrence. Familial/genetic cancer has a rate of 15%, while sporadic carcinoma has a rate of 80 to 90%. A meta-analysis of several studies found that the cancer risk is higher for men who have a brother who has been diagnosed with cancer rather than a father. The most and that the genealogical risk is higher for early-onset disease .
7. Non-dietary environmental risk factors
Smoke from burning tobacco is considered a carcinogen for many human malignancies, both submissive and non-submissive. Regardless, determining its causal link with prostate cancer has been a lengthy procedure. Because tobacco smoke carcinogens work explicitly, producing DNA mutations, and indirectly, causing hormone metabolism alterations, the causal link with prostate cancer is biologically reasonable. Some researchers have discovered a link between smoking and specific genetic variants that are linked to an increased risk of prostate cancer .
7.2 Socio-economic factors
All social elements, including economic, lifestyle, scholastic, and intellectual aspects, do not appear to influence the risk of prostate cancer on their own. Despite this, they are indirectly involved by influencing dietary factors, occupational exposure, and access to health systems, both for timely detection and appropriate treatment, and they are unquestionably involved by influencing dietary factors, occupational exposure, and acquisition to health systems [12, 13, 14, 15].
7.3 Other genetic changes
Other genes that may support a heightened risk of developing prostate cancer include
7.4 Occupational risk factors
Prostate cancer is thought to be caused by a variety of occupational variables. Farmers/agricultural workers, chemicals (organochlorine insecticides), shift work, and flight personnel are also risk factors .
The most often used pesticide/insecticide was lead arsenate. Its use was reduced, but not stopped, until 1988, due to later discoveries of its harmful health consequences. In the United States, however, the usage of lead arsenate has poisoned most of the farmed land. Many workers are expected to develop cancer as a result of its carcinogenic qualities. Most frequently used insecticides are organochlorine pesticides, organophosphorus pesticides, carbamates, concerning to and triazines [51, 52, 53, 54, 55, 56]. Ancestry is also important in the interplay between pesticide susceptibility and ancestry. When exposed to pesticides, a person with a family history of prostate cancer has a significantly increased risk of prostate cancer, which has been confirmed for carbamates, fonofos, chlorpyrifos, and phorate. Evidence is also presented that pesticide exposure causes cancer to become more aggressive.
7.6 Organochlorine pesticides
In Swedish and American research, rational results demonstrated a link between organochlorine pesticides and a significantly elevated incidence of prostate cancer. In a Swedish study, chlordane was shown to be the most dangerous organochlorine pesticide, whereas heptachlor, 2,4-dichlorophenoxyacetic acid (2,4-D), and lindane were found to be the most dangerous. Certain review articles support a bit that pesticides may elevate the prostate cancer risk minimally. The specific pesticide that is responsible for the increased risk is not yet discovered .
7.7 Shift work
Shift work is usually classified as work that is not done during the day. As a result, continual night shift work is classified as shift work. There is a strong link between shift work exposure and prostate cancer. Because of the various exposure conditions, the degree of variability is fairly significant. A meta-analysis conducted by Krstev et al. and prior meta-analyses provided evidence that shift employment, including night work, can raise the risk of prostate cancer .
7.8 Flight personnel
A great number of researchers have looked into the risk of cancer in-flight crew members. Because flight crews frequently travel across multiple time zones, they are sometimes thought to be representatives for circadian rhythm disturbance. They are, nonetheless, subjected to carcinogenic ionizing cosmic radiation . They are, nonetheless, subjected to carcinogenic ionizing cosmic radiation. Cancer risk might be increased as a result of several exposures. According to a meta-analysis undertaken by Krstev et al., pilots had a considerably increased risk of prostate cancer. It is difficult to explain the variation between the pilots and cabin crew by circadian rhythm disorder or cosmic radiation and could be due to unrestricted distraction . The evidence implies that there may be a link between pilots and prostate cancer.
A farmer’s job entails a variety of responsibilities, including animal care, dealing with feed, seed, and animal waste, salvaging hay and other grains, driving tractors and other vehicles, operating various machines, and performing maintenance and repairs. As a result, they are exposed to organic and inorganic dust, pesticides, fungus, germs, viruses, lubricants, diesel exhaust, and welding fumes, and ultraviolet light [49, 50, 51, 52, 53]. Due to a variety of exposures, numerous studies have suggested an increased prostate cancer risk in farmers compared to other occupations.
PSA (prostate-specific antigen) is a substance produced by the prostate gland. High PSA readings can indicate prostate cancer, prostatitis (a noncancerous illness), or an enlarged prostate gland. The prostate-specific antigen (PSA) test is the most widely used prostate cancer screening method. This is a straightforward blood test that determines the amount of PSA in your circulation. This test is usually the first step in any prostate cancer diagnosis. Nonetheless, PSA screening alone cannot determine whether cancer is present. The PSA test is also used to monitor the effects of treatment for prostate cancer, such as surgery, radiation, hormone therapy, and chemotherapy . When a man undergoes treatment for prostate cancer, his PSA level will plunge significantly. Conventional screening with PSA is one of the tools the physician will use to measure if cancer has recurred. Biochemical recurrence occurs when PSA levels rise to a certain threshold following prostate cancer treatment. This means that some cancer cells have managed to survive and are now releasing PSA. If this occurs, the doctor will schedule additional testing and suggest additional treatment options.
8. Prostate cancer treatment
8.1 Surgery for prostate cancer
A radical prostatectomy is the main type of surgery for prostate cancer. In this operation, the surgeon removes the complete prostate gland and additionally some of the tissue around it, including the seminal vesicles . This includes:
In the more conventional approach to prostatectomy, called an open prostatectomy, the surgeon operates through a single long skin incision (cut) to eliminate the prostate and surrounding tissues whereas, in a laparoscopic prostatectomy, the surgeon makes numerous minor incisions and uses extraordinary long surgical tools to eliminate the prostate. The surgeon either holds the equipment straight away or uses a control panel to specifically move robotic arms that clasp the equipment . This technique of prostatectomy has become more common in recent times. If done by experienced surgeons, the laparoscopic radical prostatectomy can provide outcomes analogous to the open approach.
8.1.1 Open prostatectomy
Open prostatectomy comprises Radical retropubic prostatectomy and Radical perineal prostatectomy.
22.214.171.124 Radical retropubic prostatectomy
For this open operation, the surgeon creates an incision in the lower abdomen, from the umbilicus down to the pubic bone. Either general anesthesia (asleep) or spinal or epidural anesthesia (drugging the lower half of the body) is given together with sedation during the surgery. If there is a plausible chance that cancer might have spread to surrounding lymph nodes (based on your PSA level, prostate biopsy results, and other conditions), the surgeon may also eliminate some of these lymph nodes at this time which is known as a pelvic lymph node dissection. The nodes are then dispatched to the laboratory to identify if they have cancer cells in them. If the cancer cells are found in any of the nodes, the surgeon might not proceed with the surgery . This is because it is doubtful if cancer can be cured with surgery and eliminating the prostate could assist with severe side effects. After the prostate is eliminated, still under anesthesia, a catheter which is a thin, flexible tube will be put in the penis to help exude the bladder. The catheter will usually stay in place for 1 to 2 weeks until healed. After the catheter is removed, patients can urinate on their own .
126.96.36.199 Radical perineal prostatectomy
In this open operation, the surgeon makes an incision in the skin between the anus and scrotum (the perineum). This strategy is used less often because it is more plausible to lead to erection problems and because the surrounding lymph nodes cannot be eliminated. But it is usually a shorter operation and might be an alternative if erections are not concerned and there is no need for the lymph nodes to be removed. It also might be used if any other medical conditions make retropubic surgery dangerous. It can be just as remedial as the retro public approach if done accurately . The perineal operation may cause less pain and an easier recuperation than the retropubic prostatectomy. After the surgery, still under anesthesia, a catheter will be put in the penis to assist exude the bladder. The catheter usually stays in place for 1 to 2 weeks until healed. After the catheter is removed, patients can urinate on their own.
8.1.2 Laparoscopic prostatectomy
If treatment with laparoscopic surgery is taken under consideration, it is crucial to comprehend what is familiar and what is not yet familiar about this approach. The most significant factors are likely to be the aptitude and experience of the surgeon. If it is decided that laparoscopic surgery is the right treatment, be sure to look for a surgeon with a lot of experience. Laparoscopic prostatectomy comprises Laparoscopic radical prostatectomy and Robotic-assisted laparoscopic radical prostatectomy .
188.8.131.52 Laparoscopic radical prostatectomy
For a laparoscopic radical prostatectomy (LRP), the surgeon inserts special long equipment through numerous small incisions in the abdominal wall to eliminate the prostate. One of the pieces of equipment has a small video camera on the end, which lets the surgeon see the interior of the body. Laparoscopic prostatectomy has some advantages over open radical prostatectomy, encompassing limited blood loss and pain, shorter hospital stays (usually no more than a day), rapid recovery times, and the catheter will need to remain in the bladder for less time . The rates of major side effects from LRP, such as erection difficulties and discomfort holding urine (incontinence) seem to be about as identical as for open prostatectomies. Recovery of bladder control may be hindered slightly with this approach. However, more long-term studies are required to compare side effects and risks of recurrence. Between open prostatectomy and laparoscopic radical prostatectomy, the success of either technique seems to be determined primarily by the experience and aptitude of the surgeon .
184.108.40.206 Robotic-assisted laparoscopic radical prostatectomy
This technique is also known as robotic prostatectomy. In this technique, laparoscopic surgery is done using a robotic system. The surgeon settles down at a control panel in the operating room and robotic arms are moved to operate through numerous small incisions in the patient’s abdomen. Robotic prostatectomy has superiority over the open approach in terms of less pain, blood loss, and healing time. But with regards to the side effects, men are most concerned about urinary and/or erection difficulties . There does not seem to be a discrepancy between robotic prostatectomy and other techniques. For the surgeon, the robotic system may provide more maneuverability and more accuracy when moving the equipment than a conventional laparoscopic radical prostatectomy. Regardless, the most important factor in the accomplishment of either type of laparoscopic surgery is the surgeon’s experience and aptitude.
8.2 Risks of prostate surgery
The risks with any type of radical prostatectomy are much like those of any major surgery. Difficulties throughout or momentarily after the operation can encompass:
Reactions to anesthesia
Loss of blood from the surgery
Blood clumps in the legs or lungs
Injury to surrounding organs
Infections at the site of surgery.
8.3 Side effects of prostate surgery
The major possible side effects of radical prostatectomy include incontinence of urine i.e., being unable to control urine and erectile dysfunction i.e., impotence; problems getting or keeping erections. These side effects can also occur with other forms of prostate cancer treatment [57, 58, 59].
Incontinence of urine: not being able to control urine or having leakage or dribbling. Being incontinent can influence not only physically but emotionally and socially as well. Some of the major types of incontinence include:
Men who lack self-restraint of stress might leak urine when they cough, laugh, sneeze, or exercise. Lacking self-restraint of stress is the most popular after prostate surgery. It’s usually induced by trouble with the bladder sphincter valve. Prostate cancer treatments can damage this valve that keeps urine in the bladder or the nerves that keep the valve functioning.
Men who lack self-restraint of overflow have trouble emptying their bladder. They take a long time to urinate and have a dribbling stream with little force. This is usually inflicted by blockage or narrowing of the bladder opening by scar tissue.
Men who lack self-restraint of urge have an instant need to urinate. This happens when the bladder becomes too susceptible to stretching as it fills with urine.
Barely after surgery, men lost all proficiency to control their urine. This is called continuous incontinence.
Chemotherapy (chemo) utilizes anti-cancer drugs injected into a vein or given orally. These drugs travel through the bloodstream to reach cancer cells throughout the body. Chemo is periodically used if prostate cancer has spread outside the prostate gland and hormone therapy has been proven futile. Contemporary research has also indicated that chemo might be beneficial if provided along with hormone therapy. Chemo is still not a conventional treatment for timely prostate cancer .
9.1 Chemo drugs in treatment of prostate cancer
Chemo drugs are typically used one at a time for prostate cancer. Some of the chemo drugs used to treat prostate cancer comprise of:
Extensively, the first chemo drug given is docetaxel, in combination with the steroid drug prednisone. If this does not function or stops functioning, cabazitaxel is usually the following chemo drug attempted (Although there may be additional treatment options as well).
Docetaxel and cabazitaxel have been indicated to help men live longer, on average than former chemo drugs. They may slow cancer’s development and also decrease its symptoms, resulting in a better quality of life. However, chemo is very improbable to remedy prostate cancer. Other chemo drugs being researched for utilization in prostate cancer include carboplatin, oxaliplatin, and cisplatin [56, 57, 58].
Chemo drugs for prostate cancer are typically given intravenously (IV), as an infusion over a certain period and some drugs, such as estramustine, are given as a pill orally. Usually, a slightly larger and sturdier IV is required in the vein system to dispense chemo. They are known as central venous catheters (CVCs), central venous access devices (CVADs), or central lines. They are used to provide medicines, blood products, nutrients, or fluids right into the blood and can also be used to take out blood for testing. Many different kinds of CVCs are available. The most common types are the port and the PICC line .
Doctors usually give chemo in cycles, with each period of treatment followed by a relaxation period to give some time to recuperate from the impact of the drugs. Cycles are more frequently 2 or 3 weeks long. The schedule differs depending on the drugs used. For example, with certain drugs, the chemo is provided only on the first day of the cycle. With other drugs, it is provided for a few days in succession or once a week. Then, at the verge of the cycle, there are repetitions of the chemo scheduled to begin the next cycle. The duration of medication for progressive prostate cancer is based on how well it is functioning and what side effects it causes [56, 57, 58].
9.2 Apparent side effects of chemotherapy
Chemo drugs invade cells that are dividing instantly, which is why they function against cancer cells. But various cells in the body, such as those in the bone marrow (where new blood cells are made), the lining of the mouth and intestines, and the hair follicles, also divide rapidly. These cells can also be influenced by chemo, which can lead to side effects. The side effects of chemo are determined by the kind and dose of drugs provided and for how long they are consumed . Various common side effects can include:
Loss of hair
Nausea and vomiting
Heightened chance of infections (from experiencing inadequate white blood cells)
Manageable bruising or bleeding (from experiencing inadequate blood platelets)
Exhaustion (from experiencing inadequate red blood cells)
These side effects are temporary and normally disappear once the treatment is finished. There are usually ways to reduce these side effects. For example, drugs can be provided to help intercept or decrease nausea and vomiting. Together with these risks, various side effects are observed more usual with particular chemo drugs. For example:
Docetaxel and cabazitaxel occasionally cause drastic allergic reactions. Medicines are provided before each treatment to help preclude this. These drugs can also destruct nerves leading to a phenomenon known as peripheral neuropathy, which can cause numbness, tingling, or burning sensations in the hands or feet.
Mitoxantrone can, very unusually, cause leukemia after several years.
Estramustine conveys an intensified risk of blood clots.
If any side effects are noticed while getting chemo, report them to the cancer care team so that they can be treated quickly. In certain cases, the doses of the chemo drugs may need to be decreased or medication may need to be impeded or ceased to obstruct the effects from getting worse.
Chemoprevention, a prophylactic strategy that utilizes non-poisonous natural or artificial compounds to alter, impede, or avert cancer by targeting certain steps in the carcinogenic pathway, is gaining adhesion among health care practitioners. Soy isoflavones and curcumin, staples of the Asian diet, have demonstrated convincing results as practical factors for the chemoprevention of prostate cancer . This is because of their proficiency to regulate various intracellular signaling pathways which comprise cellular proliferation, apoptosis, inflammation, and androgen receptor signaling. Contemporary information has disclosed that the DNA damage response (DDR) is one of the timeliest incidents in the multistep advancement of human skin cancers to aggressive malignancy. Soy isoflavones and curcumin stimulate the DDR, providing an alternative and justification for their clinical application in prostate cancer chemoprevention.
The prostate cancer risk can be ameliorated by approximately 30% by soy food consumption. Elevated soy consumption is correlated with localized prostate cancer reduction even among Japanese men with a significantly high soy intake concerning Caucasians. Moreover, a lower mortality rate from prostate cancer was correlated with soy consumption. The level of PSA decreases in prostate cancer patients simply because of the customary consumption of soy. Lately, it has been reported that the widespread presence of equal production, a potential risk factor for prostate cancer, is decreasing in the young generations of Korea and Japan [53, 54, 55, 56, 57, 58].
Some of the important points to take into consideration are that chemoprevention must be safe, sustain the quality of life, reduce the occurrence, consequence, and harshness of the disease and be economically feasible. Of all the drugs that have demonstrated greater scientific evidence in clinical trials, worth mentioning are inhibitors of the enzyme 5-α reductase, which converts testosterone into dihydrotestosterone and two isoforms exist, type 1 and type 2 exist for this.
Dutasteride is an influential inhibitor of 5-α reductase and is 45 times stronger than finasteride in hindering type 1 isoform and twice as strong on isoform 2. Undoubtedly, this is a guaranteeing drug in the prevention of prostate cancer in the risk population . Among the scores of biomarkers being studied, numerous markers and techniques deserve awareness because of the promising published data indicating that better prostate cancer screening methods will be available in the coming times that will maintain non-aggressiveness and acceptability for both patients and urologists in clinical practice.
Conflict of interest
The authors declare a conflict of interest as none.