Cancer Risk Evaluation and Screening

A cancer risk factor is anything that increases a person’s chance of getting cancer. Yet most risk factors do not directly cause cancer. Some people with several risk factors never develop cancer. And others with no known risk factors do. Before looking into the risk evaluation, it is important to understand how cancer develops and the main cancer types.

All cancers start with damage in the genes, called mutations. Gene mutations can be inherited or can occur from environmental exposure. That is why cancer is often divided into hereditary cancer and sporadic (non-hereditary) cancer.

Hereditary types of cancers run in families. Each person inherits one copy of each gene from their mother and one copy from their father. If one of the parents has a gene with a mutation, he/she can pass this mutation to their children. The children will become more likely to develop cancer than people who don’t have this mutation. However, just having a mutation does not always cause cancer.

When it comes to an inherited risk for cancer, it’s essential to keep in mind that an individual doesn’t directly inherit cancer itself, but rather the risk of developing it. The development of cancer requires the occurrence of a mutation in a cell during an individual’s lifetime, leading to further DNA errors in that cell and ultimately resulting in cancer growth. This fundamental concept is known as the “two-hit hypothesis,” which was first introduced by Alfred Knudson in 1971 and led him to win the Nobel Prize for his discovery.

It’s important to note that despite having an inherited risk for cancer, approximately 40% of individuals with a hereditary risk for breast cancer will not develop the disease. This highlights the fact that while inherited mutations can increase the likelihood of cancer development, most cancers stem from mutations that arise over time due to aging, environmental factors, viruses, and other similar factors.

Some factors can indicate that one has a higher risk of developing cancer. They include:

• A family history of cancer, particularly in multiple family members or in family members who were diagnosed with cancer at a young age
• A personal history of cancer, particularly if it occurred at a young age
• A family history of multiple different types of cancer, when one relative develops 2 or more types of cancer.
• A family history of rare cancers that are associated with specific genetic mutations, such as ovarian cancer, adrenocortical cancer, or sarcoma.

It’s important to note that having one or more of these factors does not necessarily mean that you have an inherited genetic mutation that increases your risk of cancer. The only way to know for sure is to undergo genetic testing.

Genetic testing can estimate your chances of developing inherited types of cancer in your lifetime. There are a few types of genetic testing available:

1. Whole genome sequencing (WGS) analyzes the whole genome, including coding, non-coding, and mitochondrial DNA. WGS is the most comprehensive way of testing the presence of an inherited risk of cancer. WGS captures large and small gene variants that might be missed with targeted approaches and can uncover disease susceptibilities years before symptoms present. This enables earlier intervention and more effective preventative care. Although WGS is a costly and time-consuming process, it is increasingly utilized in cases where a tumor has already been identified at an advanced stage. By performing WGS on tumor cells and comparing the results to the genetic profile of healthy tissue, clinicians can gain valuable insights into how the tumor may respond to specific cancer therapies, allowing for more personalized and effective treatment with minimal side effects. This powerful approach is known as tumor profiling and is helping to transform the landscape of cancer care.
2. Whole exome sequencing (WES) analyzes only the specific areas of DNA, which are protein-coding regions of the genome and are called exons. So, it provides information on only about 1,5-3% of the total DNA. However, it has its advantages. Because sequencing is done on a much smaller scale, it allows sequencing exomes at a much greater depth. This greater depth allows the investigation of particular DNA areas more pricelessly. WES is usually used to reveal mutations in target disease-associated genes. It has a lower cost compared to WGS. The same as WGS, WES is also used for tumor profiling. So it provides a clearer picture of genetic abnormalities that affect tumor progression and helps clinicians use precision medicine to decide how to treat certain cancer.
3. Targeted genotyping is a highly efficient and cost-effective approach to genetic analysis, allowing researchers to focus specifically on areas of the genome that are known to vary between individuals. This customizable method can be tailored to include non-protein coding genes that may be relevant to certain types of cancer, such as leukemia or breast cancer. With the ability to sequence both DNA and RNA, targeted genotyping has become an even more powerful tool in the fight against cancer. RNA sequencing, in particular, can provide valuable insights into how genes are expressed, shedding light on the underlying molecular mechanisms that drive cancer growth and progression. By harnessing the power of targeted genotyping, clinicians and researchers can better understand the genetic factors that contribute to cancer and develop more effective treatments for patients.

If you decide to proceed with genetic testing, there are a few things that you might want to think about or do in advance.

• Before testing, learn about your family’s medical history. It can help you and your healthcare team determine whether genetic testing is likely beneficial and which test might be best for you.
• Find out whether any of your relatives have already had genetic testing. If any of your relatives have tested positive for an inherited mutation, their genetic testing report could be very informative for your healthcare provider and help him to tailor testing to your needs.
• If you are the first to undergo genetic testing in your family, it would be good to collect your family medical history, including all close relatives who were diagnosed with cancer, the type of cancer they had, and their age at diagnosis.
• Think about how you will cope with test results in case they are positive, and discuss possible strategies for minimizing the risk with your healthcare provider or genetic counselor.

Sporadic cancer or non-hereditary cancer occurs spontaneously and is not passed down from generation to generation. These types of cancer are not caused by inherited genetic mutations. In most sporadic cancer cases, the genetic mutations that lead to cancer development occur during a person’s lifetime and are absent at birth.

These mutations can be caused by various factors, including exposure to environmental toxins, lifestyle factors (such as tobacco use), and the natural aging process. Sporadic cancers are the most common type of cancer and can affect any part of the body.

There are many different risk factors for non-hereditary cancer, and the specific factors that increase your risk can vary depending on the type of cancer.¹ Jurdana, Mihaela. “Physical activity and cancer risk. Actual knowledge and possible biological mechanisms.” Radiology and oncology vol. 55,1 7-17. 12 Jan. 2021. PubMed Source ²Liao, John B. “Viruses and human cancer.” The Yale journal of biology and medicine vol. 79,3-4 (2006): 115-22. PubMed Source Some most common risk factors for non-hereditary cancer include:

• Exposure to certain chemicals or radiation, such as tobacco smoke, ultraviolet radiation, or certain viruses and bacteria (such as human papillomavirus (HPV), hepatitis B and C, Helicobacter pylori, Epstein–Barr virus).
• Certain lifestyle factors, such as poor diet, lack of exercise, excessive alcohol consumption, and smoking.
• A family history of cancer, although this is not the same as having an inherited genetic mutation that increases cancer risk
• A personal history of certain medical conditions, such as obesity or chronic inflammation.
• Age and gender, as the risk of developing certain types of cancer, increases with age, and some types of cancer are more common in men or women.

It’s important to note that having one or more of these risk factors does not necessarily mean you will develop cancer. However, you can reduce your risk of developing cancer by stopping risky behaviors. These include using tobacco and alcohol, being overweight, and getting multiple sunburns.

A medical provider can identify your risk of developing sporadic cancer based on your health history and lifestyle, but some tests can help find cancer before signs or symptoms appear. This is called cancer screening. Screening tests can help find cancer early before symptoms appear and when it is much easier to treat cancer.

Cancer screening tests aim to find cancer before it causes symptoms and when it may be easier to treat successfully. For example, lung and cervical cancers are the most common types without inherited components, and survival improves when cancer is detected early. However, ~50% of cancers are at an advanced stage when diagnosed.

1. Multi-cancer early detection tests can potentially find more than one type of cancer from a single sample of blood. These tests analyze the mutated, fractionated DNA and RNA from cancer cells in your blood. Different multi-cancer early detection tests are being developed, but many are not yet FDA-cleared or approved. One of the tests available now by prescription through a doctor is the GRAIL Galleri test.³ The Promise of Multi-Cancer Early Detection URL It can detect more than 50 types of cancer from a single blood draw.
2. Targeted screening tests for some types of cancer. These screening tests are proven to be an effective screening method for certain types of cancer and have been successfully used for decades in medical practice. These screening methods are developed for the following types of cancer: breast, cervical, colorectal, head and neck, lung, prostate, and skin cancers. More information about these screening tests can be found here. The problem many types of cancer do not yet have an effective screening method. Developing new cancer screening tests is an area of active research now.
3. Whole-body MRI scanning is an imaging method without ionizing radiation that can provide pictures of your entire body. Whole-body MRI can be used to detect and locate cancerous lesions. However, it is currently recommended for cancer screening in people with high hereditary cancer predisposition.⁴ Petralia, Giuseppe et al. “Whole-body magnetic resonance imaging (WB-MRI) for cancer screening: recommendations for use.” La Radiologia medica vol. 126,11 (2021): 1434-1450. PubMed Source The number of studies describing the use of whole-body MRI for the early detection of tumors in asymptomatic people is increasing. But the efficacy of this method in the general population is not very well proven yet, and research in this direction is still ongoing.⁵ Zugni, Fabio et al. “Whole-body magnetic resonance imaging (WB-MRI) for cancer screening in asymptomatic subjects of the general population: review and recommendations.” Cancer imaging : the official publication of the International Cancer Imaging Society vol. 20,1 34. 11 May. 2020. PubMed Source It is widely used in people with certain cancer types to see if the tumors are spreading through the body.⁶ Summers, Paul et al. “Whole-body magnetic resonance imaging: technique, guidelines and key applications.” Ecancermedicalscience vol. 15 1164. 7 Jan. 2021. PubMed Source
4. Biomarkers are the molecules that can be detected in the serum from a blood sample and may indicate the presence of cancerous cells. Some blood biomarkers can be used for screening certain types of cancer.⁷ Zong, Jingjing et al. “Serum Tumor Markers for Early Diagnosis of Primary Hepatocellular Carcinoma.” Journal of hepatocellular carcinoma vol. 7 413-422. 18 Dec. 2020. PubMed Source ⁸ Wild, Norbert et al. “A combination of serum markers for the early detection of colorectal cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research vol. 16,24 (2010): 6111-21. PubMed Source One example is CA-125 which is often used as a screening test for ovarian and uterine cancers.⁹ Nisenblat, Vicki et al. “Blood biomarkers for the non-invasive diagnosis of endometriosis.” The Cochrane database of systematic reviews vol. 2016,5 CD012179. 1 May. 2016. PubMed Source However, biomarkers tests are usually used to look for genes, proteins, and other substances that can provide additional information about already existing cancer and help select the best treatment.
5. Biopsy is a medical test that involves removing a small tissue sample from the body for examination. The sample is usually taken from an area of the body with signs of a disease or abnormal growth. The tissue sample is then examined under a microscope by a pathologist, who looks for abnormalities that may indicate the presence of cancer. Biopsies can be performed using various techniques, including fine needle aspiration, core needle biopsy, excisional biopsy, and incisional biopsy. The specific technique used will depend on the location and type of tissue being sampled and the reason for the biopsy. It is usually used in combination with other tests, such as imaging tests and blood tests. To learn more about different types of biopsy and how it is performed, please see here.

Breast cancer: women between age of 40 to 44 should have the choice to start annual breast cancer screening with mammograms if they wish to do so. Starting at age 45, women should undergo mammography every year.

Cervical cancer: Women aged 25 to 65 should undergo a Pap test every three years. Women aged 30 to 65 can also undergo human papillomavirus (HPV) testing every five years. After 65 years old, no testing is needed if the previous testing was with normal results.

Colorectal cancer: Men and women aged 45 to 74 should undergo regular colorectal cancer screening. People aged 76 to 85 should talk with their healthcare provider about whether continuing screening is right for them.

Prostate cancer: starting at age 45, men at higher-than-average risk of prostate cancer should talk with a doctor about the benefits of being tested. Men aged 50 to 74 with an average risk of prostate cancer should talk to their healthcare provider about the potential benefits and risks of prostate cancer screening.

Lung cancer: starting at age 45, discuss with your doctor your history of smoking and decide if and how often you need to undergo testing.