Prostate Cancer
Prostate cancer is the second most common cancer in men after skin cancer and the second leading cause of cancer death in men after lung cancer. Risk factors for prostate cancer include increased age, family history and black race
Overview
Prostate cancer is the second most common cancer in men after skin cancer and the second leading cause of cancer death in men after lung cancer. Risk factors for prostate cancer include increased age, family history and black race. In early stages, prostate cancer is asymptomatic and is typically detected by screening. Although many prostate cancers are sporadic, about 5-15% of prostate cancer diagnoses may be associated with a strong hereditary component. Genetic testing has found its place in routine testing for breast, ovarian and prostate cancers amongst others, providing actionable preventive measures to increase life expectancy and quality of life.
Hereditary cancer syndromes are encountered in all medical specialties. Although they account for about 5% of all malignancies, it is of special importance to identify these patients because, unlike patients with sporadic cancers, they require special, long-term care as their predisposition can cause them to develop certain tumors at a relatively early age. Most hereditary cancers are associated with a “germline mutation” that will be present in every cell of the human body. Identification of patients at risk of inherited cancer susceptibility is dependent upon the ability to characterize genes and alterations associated with increased cancer risk as well as gathering a detailed personal and family history aiding in the identification of the mode of inheritance as well as other family members at risk of suffering from this susceptibility. Most hereditary cancer syndromes follow an autosomal dominant inheritance, and the penetrance is high.
The Igenomix Prostate Cancer Precision Panel provides a comprehensive analysis of the most common genes responsible for the development of a malignant growth in the prostate using next-generation sequencing (NGS) to fully understand the spectrum of relevant lung cancer predisposition genes.
Indication
The Igenomix Comprehensive Inherited Caner Precision Panel is indicated as a screening and diagnostic test in those cases where there are:
- Family history of prostate cancer
- Blood in the urine
- Frequent urination
- Urge to urinate
- Pain or burning during urination
- Weak or interrupted urine flow
- Fatique
- Lower back pain
- Change in bowel habits
- Unintentional weight loss
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular diagnosis for an accurate clinical diagnosis of a patient with personal or family history suggestive of a hereditary cancer syndrome with predisposition to prostate cancer.
- Early initation of treatment with a multidisciplinary team for appropriate total body screening, early surgical intervention, or pharmacologic treatment.
- Risk assessment and genetic counselling of asymptomatic family members according to the mode of inheritance.
- Reduce morbidity related toprostate cancer, or morbidity secondary to complications of surveillance and treatment.
- Categorization of genetic alterations into predictive levels of standard, investigational or hypothetic target therapies in the molecular pathology reports.
- Improved pathways from diagnosis to treatment in susceptible populations.
See all genes and diseases
Gene | OMIM Diseases | Inheritance* | % Gene Coverage (20x) | HGMD** |
APC | ColorectalCancer,Gastric | AD | 98.92 | 1846 of 1882 |
AR | Androgen Insensitivity | AD,X,XR,G | 97.96 | NA of NA |
BARD1 | Breast Cancer, Hereditary | AD | 99.86 | 195 of 195 |
BMPR1A | Hereditary Mixed Polyposis | AD | 100 | 124 of 127 |
BRCA1 | Breast Cancer, Familial | AD,AR,MU | 98.97 | 2783 of 2894 |
BRCA2 | Breast Cancer, Breast-Ovarian | AD,AR,MU | 98.51 | 3343 of 3451 |
BRIP1 | Breast Cancer, | AD,AR | 94.97 | 235 of 237 |
CDH1 | Blepharocheilodontic | AD | 100 | 361 of 363 |
CDKN2A | Melanoma-Astrocytoma | AD | 94.99 | 257 of 262 |
CHEK2 | Breast Cancer, Li-Fraumeni | AD | 99.47 | 307 of 310 |
EPHB2 | ProstateCancer/ | AR | 98.08 | 12 of 12 |
GREM1 | Hereditary | 99.89 | 5 of 5 | |
KLF6 | Gastric Cancer, | AD | 100 | 1 of 1 |
MAD1L1 | ProstateCancer | AD | 100 | 2 of 2 |
MDM2 | Lessel-Kubisch Syndrome, | AR | 99.92 | 1 of 1 |
MLH1 | Hereditary Nonpolyposis | AD,AR | 99.94 | 1079 of 1118 |
MRE11 | Ataxia-Telangiectasia-like | AR | 99.95 | NA of NA |
MSH2 | Lynch Syndrome, | AD,AR | 99.99 | 1032 of 1057 |
MSH6 | HereditaryNonpolyposis | AD,AR | 99.28 | 613 of 641 |
MXI1 | ProstateCancer | AD | 94.55 | NA of NA |
NAB2 | SolitaryFibrousTumour/ | 99.43 | NA of NA | |
NBN | Aplastic Anemia, Acute | AR,MU,P | 100 | 200 of 200 |
PALB2 | Breast Cancer, | AD,AR | 98.78 | 601 of 617 |
PTEN | Cowden Disease, | AD | 99.97 | 609 of 629 |
RAD50 | Nijmegen Breakage | AR | 99.94 | 117 of 120 |
RAD51 | Breast Cancer, Fanconi | AD | 99.98 | 16 of 16 |
RAD51C | FamilialBreast-OvarianCancer, | AR | 100 | 130 of 130 |
RAD51D | Hereditary Breast And | 100 | 97 of 97 | |
RNASEL | HereditaryProstate | AD | 99.83 | 7 of 7 |
RNF43 | Sessile Serrated Polyposis | AD | 99.98 | 13 of 13 |
STAT6 | SolitaryFibrousTumour/ | 99.78 | NA of NA | |
TP53 | Basal Cell Carcinoma, | AD,MU,P | 98.92 | 557 of 563 |
ZFHX3 | Prostate | AD | 99.14 | 8 of 8 |
*Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial.
**Number of clinically relevant mutations according to HGMD
References
National Comprehensive Cancer Network. (2021). Retrievedfrom https://www.nccn.org/professionals/physician_gls/default.aspx#detection
Zhen, J. T., Syed, J., Nguyen, K. A., Leapman, M. S., Agarwal, N., Brierley, K., Llor, X., Hofstatter, E., &Shuch, B. (2018). Genetic testing for hereditary prostate cancer: Current status and limitations. Cancer, 124(15), 3105–3117. https://doi.org/10.1002/cncr.31316
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Tan, S. H., Petrovics, G., &Srivastava, S. (2018). Prostate Cancer Genomics: Recent Advances and the Prevailing Underrepresentation from Racial and Ethnic Minorities. International journal of molecular sciences, 19(4), 1255. https://doi.org/10.3390/ijms19041255
Heise, M., & Haus, O. (2014). Dziedzicznyrakgruczołukrokowego [Hereditary prostate cancer]. Postepyhigieny i medycynydoswiadczalnej (Online), 68, 653–665. https://doi.org/10.5604/17322693.1104682
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