Risk Factors for Prostate Cancer

A man’s lifetime risk of developing prostate cancer is 1 in 7. Some men with prostate cancer remain asymptomatic and die from unrelated causes. This is because cancer occurs when the man is already at an advanced staged, and the tumor grows slowly.[1] Treatment can be administered when it starts becoming symptomatic, and although not cured, it can be controlled. The person may die of other diseases because they are more severe and the person is at an advanced age. The estimated number of men who have prostate cancer that is present but not detected or diagnosed during a patient’s lifetime is higher than the number of men who have clinically recognized the disease. Many tests have been designed to understand better the genetic and biologic mechanisms that determine why some prostate cancers remain clinically silent while others cause severe, life-threatening illness.[1]*Modified from National Cancer Institute Data The three most recognized risk factors are age, race, and family history of prostate cancer.

Age

Age is a significant risk factor for prostate cancer. It is rarely seen in men younger than 40 years old. The probability of being diagnosed with prostate cancer is 1 in 325 for men 49 years or younger. 1 in 4 men aged 50-59 years. 1 in 17 for men aged 60-69. 1 in 10 for men aged 70 and older with an overall lifetime risk of 1 in 7.[1]

Race

The risk of developing and dying from prostate cancer is higher among blacks, intermediate among whites, and lowest among Asians.[5,6] Differences in incidence among populations worldwide further address the race.

Family History

As with breast and colon cancer, prostate cancers cluster in families.[7-11] Five to ten percent of prostate cancer is believed to be caused by high-risk inherited genetic factors. A person who has a brother or father with prostate cancer increases his risk of prostate cancer. The relative risk for a person with a brother with prostate cancer is 3.14. It is 2.35 when he has a father who has prostate cancer and 2.25 with any relative with prostate cancer. Most of this data has been obtained from Swedish population-based family cancer database that contain more than 11.8 million men and among whom 26,651 men who are verified with prostate cancer and of which 5,623 were among related families.[12] The RR increases to 8.5 when a father and two brothers are affected and increases to 17.7 when three brothers are diagnosed with prostate cancer. The risk also increases with age in affected families and is about 5% by age 60, 15% by age 70, and 30% by age 80. As compared to the average population, where the risk is 0.45%, 3% and 10% by the same periods in the general population. The risk of prostate cancer also increases in men who have a family history of breast cancer in a mother or sister. These clusters of prostate cancer in some families may be due to genetic mutations such as BRCA1 and BRCA2 genes.[13-16] Members of such families may benefit from genetic counseling.

Differences in Incidence Among Populations Worldwide

Prostate cancer exhibits tremendous differences among populations worldwide. There is a 60 to 100-fold difference in the incidence of cancer in countries with low rates of prostate cancers when compared to countries with high rates of prostate cancer.[2] In Asia, men have an age-adjusted incidence rate of 2 to10 cases per 100,000 men. African American men have the highest incidence of prostate cancer with a 60% higher incidence than white men.[3] Among white men, northern European countries have a higher incidence than other countries.  These differences may be due to multiple factors. They include genetic, environmental, access to healthcare as well as differences in screening and treatment. Gaps in screening practice may also affect prostate cancer diagnosis. An analysis of population-based data from Sweden suggested that a diagnosis of prostate cancer in 1 brother leads to an early diagnosis in the second brother using PSA screening. This may account for prostate cancer diagnosis in younger men seen in national incidence data.

Other Modifiers of Prostate Cancer Risk

Some dietary risk factors may affect prostate cancer risk. These include fat and or meat consumption,[17] lycopene,[18-19] and nutritional products including calcium and vitamin D.[20] Phytochemicals and plant-derived compounds may play a role in prostate cancer prevention.[21] Asian men typically consume soy products that contain phytoestrogens, and this may contribute to lower incidence. Alcohol does not increase the risk of prostate cancer. However, smoking may increase the risk. Obesity may also increase the risk of prostate cancer. One study found that there was an increase in prostate cancer risk with Vitamin E supplement.

Risk of Developing a Second Cancer after Developing Prostate Cancer

Risk of developing second cancer after acquiring prostate cancer Radiation therapy as initial treatment of prostate cancer was found to increase bladder and rectal cancers as well as carcinoid malignancies. There is also an excess risk of pancreatic cancer and melanoma. In the Swedish study of 18,207 men with prostate cancer, 560 developed a second malignancy, and the RR was increased for colorectal, kidney, bladder, and squamous cell carcinoma. Having a family history of prostate cancer increased the risk of bladder cancer, myeloma, and squamous cell skin cancer.

Inheritance of Prostate Cancer Risk

Some studies have suggested that familial clustering of disease among men with early-onset prostate cancer was best explained by the presence of a rare frequency of 0.003 autosomal dominant, highly penetrant gene allele. Hereditary prostate cancer genes were predicted to account for almost 50% of all patients who have prostate cancer diagnosed at age 55 years or younger.

4K Test to reduce Overdiagnosis and Detect Aggressive Cancer

The 4K score identifies the risk of aggressive prostate cancer if a patient has an abnormal DRE or elevated PSA and is especially useful in deciding whether to proceed with a biopsy. It has accuracy in predicting aggressive cancer and predicting metastasis 20 years before it occurs. It also has the ability for patients to set personal thresholds for themselves along with their care provider based on their age, life expectancy, and health.

Previously, age-specific PSA, PSA velocity, and PSA density were used to improve the specificity of PSA to detect prostate cancer. However, recent studies have suggested that PSA density is an invasive procedure requiring a rectal ultrasound. Moreover, it does not provide much more information that PSA alone.

The 4K Test combines four prostate-specific kallikrein assay results with clinical data in an algorithm that calculates the individual patient’s percent risk for aggressive prostate cancer. In a prospective, blinded, multicenter US study the 4Kscore Test showed higher accuracy than PSA, PHI and PCA3 in predicting aggressive prostate cancer.

It is essential to address patients understanding of their family history, whether there are any cancer syndromes in their family, comorbidities, age and get a yearly PSA. MRI every 3 to 5 years is useful since the goal is to detect cancer early and determine the best way to manage these risks. Genetic counselors can help in counseling, so patients know their actual risks and how they should act on them. A home genetic test can help patients concerned about their cancer risks.

Patients hear they’re at increased risk of malignancy, but don’t understand the degree of risk. Sometimes patients are told they have a 15% lifetime risk of prostate cancer and are concerned. However, ‘that’s everybody’s risk.’ They’re not at high risk; that’s an average risk. Those tests are associated with an increased risk of prostate cancer but not necessarily an increased risk of aggressive prostate cancer. That’s cancer we want to diagnose—not nonaggressive prostate cancer. Are patients at risk of developing cancer when they’re 75, or 55? Our evaluation and management will be different depending on the clinical scenario. On the horizon, there will be clear genetic tests, and we’ll need to design clinical care to alter the identified risks. If we tell patients they have increased the risk of disease, but don’t do anything to change that risk, and we have not improved patients’ lives; we’ve made their lives worse.

Genetic Testing: Up to 10% of patients with metastatic or advanced prostate cancer and 3% of patients with localized prostate cancer carry a disease-causing variant in a DNA repair gene and other genes conferring risk for hereditary cancer disorders.     Invitae’s Detect Hereditary Prostate Cancer is a sponsored, no-charge genetic testing program that uses the Invitae Multi-Cancer Panel. This comprehensive cancer panel tests genes associated with hereditary cancer syndromes, including all known prostate cancer genes.     Determining the germline genetic etiology of prostate cancer provides eligibility for precision medical and surgical treatment options and eligibility to participate in clinical trials. This information can also be used to enable surveillance for, and early detection of, other DNA repair-related cancers in the patient and provide recommendations for early detection in
at­-risk relatives.

References:

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