Is Cancer Hereditary?

Mutations in genes – which is the unit responsible for passing on genetic information and traits from parent to offspring – is responsible for all cancers. Genes can be damaged due to a number of factors such as environmental toxins, exposure to radiation or certain chemicals, smoking and other lifestyle choices. Over time, the damage in genes accumulates, prompting uncontrolled growth of cells that lead to cancer. 

While some mutations occur as a result of external factors, other types of gene mutations are inherited. Cancers which occur as a result of inherited mutation are known as hereditary cancers. 

The signs of hereditary cancer can be as simple as having a single family member with a cancer diagnosis. Other signs may not be as obvious and involve a closer look at family members spanning several generations in order to trace familial patterns of cancer. Specific gene mutations are linked to various types of cancer. 

The most common cancer that is hereditary is breast and ovarian cancer syndrome or HBOC caused by BRCA1 and BRCA2 gene mutations. 

This article discusses four different cancer types and the possibilities of their being hereditary.

When certain breast cells become abnormal and begin to multiply uncontrollably, the result is breast cancer. Although the condition is more common in women, breast cancer can also affect men. Breast cancer most commonly begins in the lining of the milk ducts (called ductal carcinoma), tumours can develop in the milk glands as well (known as lobular cancer).

The common symptoms of breast cancer include a painless lump in the breast, bloody discharge from the nipples, redness of the breast in non-lactating women, nipple retraction inwards, dimpling or skin irritation, thickening of the nipple or skin on the breast and a lump in the underarm.  

Most breast cancer cases as per the U.S. National Institute of Health (NIH) are not hereditary, that is, there are no inherited genetic factors in most cases. These cancers, instead are linked to ‘somatic mutations’ which are genetic alterations that are not passed onto future generations.

Inherited mutations in two genes, namely BRCA1 and BRCA2, is linked to HBOC (Hereditary Breast and Ovarian Cancer Syndrome) where multiple breast and/or ovarian cancer cases are found in the same family. The risk of HBOC in a family increases with one or more of the below:

• An ovarian or breast cancer diagnosis in one or more women at age 45 or below
• Breast cancer diagnosis before age 50 in one or more women in addition to family history of other cancers such as pancreatic cancer, melanoma and prostate cancer.
•  Diagnosis of breast/ovarian cancers in same said of family across multiple generations; for instance, having both an aunt and grandmother on mother’s side  diagnosed with breast or ovarian cancer.
• Diagnosis of second breast cancer in the other breast or same breast or has both ovarian and breast cancer
• A male relative with breast cancer
• History of pancreatic or prostate cancer on the same side of family

The risk of developing breast cancer depends on the gene that is involved in hereditary breast cancer. For instance, BRCA1 and BRCA2 mutations have an inheritance pattern that is autosomal dominant. This means one copy of a mutated gene in one parent is enough to increase breast cancer risk in the offspring even when the other parent has a normal gene. 

Mutation in another gene known as tumour protein p53 or TP53 is also linked to an increased risk of developing hereditary breast cancer, although this is not common.

While not being as common as BRCA gene mutations, other genetic conditions are also associated with an increased risk of breast cancer including:

• Peutz-Jegher syndrome – This is a condition where noncancerous growths or polyps develop in the intestine and stomach and are linked to mutation of STK11 gene. This syndrome increases the risk of developing cancers including breast cancer.
• Cowden’s syndrome: Mutation in PTEN gene causes Cowden’s syndrome where multiple non-cancerous growths occur in skin, mucous membranes and other parts of the body.
• Diffuse stomach cancer: Also known as Hereditary diffuse gastric cancer (HDGC) this cancer occurs due to alterations in E-cadherin (CDH1) gene. This gene mutation is passed on from generation to generation and increases the risk of breast cancer in women.

A retrospective study by Strand Life Sciences published in the Journal of Human Genetics indicates BRCA gene mutations are three times higher in Indian women as compared to the western world. 

Another important finding of the study was that 20 percent of patients who tested positive for BRCA gene mutation had no family history. While stressing on the need for extensive studies in India to gather data on inherited BRCA mutations, researchers also pointed out that diagnosis of breast cancer could be missed out in one out of five individuals if an individual undergoes genetic testing based on family history alone.

Having an inherited mutated gene does increase breast cancer risk significantly. However, there are other factors that are linked to cancer development, such as age, environmental factors and lifestyle.

Genetic testing and genomic profiling of first degree relatives of breast cancer patients is however recommended by the researchers. If the mutation is found, preventive measures with a breast cancer specialist and adequate screening can help ensure timely diagnosis and treatment.

Surgery is the most common treatment option for breast cancer. Depending on the size and extent of the tumour, the surgeon may opt to do lumpectomy or mastectomy. Radiation and/or chemotherapy are typically recommended after surgery to prevent cancer recurrence and to kill any remaining cancerous cells. Hormone therapy is recommended for hormone receptor positive breast cancers.

Prostate cancer is one of the top ten cancers in India. In 2018, about 25,696 new cases were diagnosed and according to “India Against Cancer” initiative, the number of prostate cancer cases may double by 2020.

Prostate cancer forms in the prostate gland that is an essential part of the male reproductive system. Prostate cancer tends to be very slow growing and significant symptoms are typically experienced only in the advanced stage.

Prostate cancer is believed to run in families suggesting involvement of genetic factors. A positive prostate cancer family history increases your risk of developing it. The risk is higher if more number of relatives are affected with the cancer, particularly younger relatives. Having a first degree relative such as a brother or father with prostate cancer, according to American Cancer Society, more than doubles the risk of developing prostate cancer.

Recent research indicates specific mutations are responsible for hereditary prostate cancer and men who have these gene mutations are at increased risk for the condition. BRCA1 or BRCA2 inherited gene mutations can increase the risk of prostate cancer in some men. BRCA 1 or  2 mutation increases the risk of developing a more severe form of prostate cancer.  

A condition known as Lynch syndrome or HNPCC (Hereditary non-polyposis colorectal cancer ) is also linked to inherited gene changes and increase the risk of prostate cancer among other cancers.

Other genes linked to an increased risk of prostate cancer include ATM, CHEK2, NBN, PALB2.

Available treatment options include surgery, hormonal therapy and radiation. Hormone therapy is given to reduce the level of androgens which promote prostate cancer.

Stomach cancer is the second leading cause of cancer related deaths worldwide and in India, the fourth in the list of the most common cancers. As per the US National Institutes of Health (NIH)  close to ten percent of stomach cancer cases have a familial origin. Having a first degree relative such as father, mother, brother or sister with stomach cancer increases the risk of developing stomach cancer.

While gene mutations have been linked to stomach cancer in some people, the exact genetic factors are not fully understood. Scientists believe a combination of environmental and genetic factors could be responsible for familial stomach cancer.

Some of the inherited conditions that increase stomach cancer risk include:

Hereditary diffuse gastric cancer (HDGC):

This is an inherited, rare condition that increases risk of stomach cancer caused by a mutation in a gene known as CDH1.

Diffuse gastric cancer also known as or “linitis plastica” or“signet ring cell gastric cancer” affects almost the entire stomach rather than any one specific area in the stomach. According to the NIH, diffuse gastric cancers account for 20 percent of stomach cancers and HDGC is responsible for a small amount of these cancers. Women diagnosed with HDGC are at an increased risk of developing breast cancer. 

Diagnosis of HDGC is made if any one criteria listed below are met apart from recommending CDH1 genetic testing:

• Families which have two or more stomach cancer cases with one of them being diffuse gastric cancer
• Diagnosis of diffuse stomach cancer before the age of 40
• Individual and/or family history of lobular breast cancer and diffuse stomach cancer with at least one person being diagnosed before 50 years of age
• Lobular breast cancer diagnosis in the family before age 50

Although genetic testing for CDH1 gene mutation is available, only about 20 to 30 percent of families with possible HDGC are found to have CDH1 gene mutation. Talking to a cancer specialist well versed in genetic conditions is the best way to understand if you are at risk for developing stomach cancer.

Lynch syndrome:

Lynch syndrome (earlier called hereditary non-polyposis colorectal cancer) is an inherited  condition which increases colorectal, stomach and other cancers. The genes implicated in Lynch syndrome include MLH1,MSH2, MLH3, PMS1, MSH6, TGFBR2 and PMS2.

Familial adenomatous polyposis:

Familial adenomatous polyposis or FAP is linked to mutations of the APC gene and is characterised by the development of multiple polyps typically in the colon but can involve the intestine and stomach as well. People with FAP have a higher risk of developing both colorectal and stomach cancer. 

BRCA gene mutations:

BRCA1 and BRCA2 are inherited gene mutations associated with an increased risk of breast cancer. Mutations in these genes are also linked to higher stomach cancer risk.

Li-Fraumeni syndrome:

Mutation in a tumor suppressor gene known as TP53 causes Li-Fraumeni syndrome which raises the risk of some cancers such as stomach cancer.

Peutz-Jeghers syndrome:

In this condition, polyps develop in the intestines, stomach, and other areas including lungs, nose, and bladder. The stomach polyps are called hamartomas and can cause problems such as blockage or bleeding in the stomach. PJS increases the risk of many cancers including stomach, pancreas, intestine and others.

Surgery

Stomach cancer that has not spread can be removed by surgery where part of the esophagus or stomach is removed where the tumour is located. Lymph nodes that are near the stomach are typically removed as well. Surgery for stomach cancer may be scheduled for the following phases of treatment:

• Removing early-stage tumors from the stomach lining. Very small cancers limited to the inside lining of the stomach may be removed using endoscopy in a procedure called endoscopic mucosal resection
• Removing a portion of the stomach (subtotal gastrectomy)
• Removing the entire stomach (total gastrectomy)
• Removing lymph nodes to look for cancer
• Removing part of the stomach may relieve signs and symptoms of a growing tumour in people with advanced stomach cancer

Radiation therapy

Radiation therapy uses high-powered beams of energy, such as X-rays and protons, to kill cancer cells. In gastroesophageal junction cancer, as well as in cancer of the stomach body, radiation therapy can be used before surgery (neoadjuvant radiation) to shrink a tumour so that it’s more easily removed. Radiation therapy can also be used after surgery (adjuvant radiation) to kill any cancer cells that might remain in the area around your esophagus or stomach.

Chemotherapy

Chemotherapy drugs travel throughout the body, killing cancer cells that may have spread beyond the stomach. Chemotherapy can be given before surgery (neoadjuvant chemotherapy) to help shrink a tumour so that it can be more easily removed. It can also be used after surgery (adjuvant chemotherapy) to kill any cancer cells that might remain in the body.

Targeted drugs

 Targeted therapy uses drugs that attack specific abnormalities within cancer cells or that direct your immune system to kill cancer cells (immunotherapy). Several targeted drugs are being studied for treatment of gastroesophageal junction cancer, but only two of these drugs — ramucirumab and trastuzumab — have been approved for this use.

Colon cancer is a malignancy that begins in the colon, or in the large intestine. It is known to start forming as benign polyps – flat, or knob-shaped growths that are present on the inner

lining of the large intestine. Occasionally, these growths are known to cause symptoms such as unexplained bleeding (the presence of blood in the stool), or constipation. However, in most cases, these polyps produce no early symptoms at all – which is why most people may not even realise when these signs are present.

Some polyps may continue to remain benign, which means that they will exist as non-cancerous masses. Some of these tumours can become malignant, or cancerous. These polyps are often detected using a procedure called a ‘colonoscopy’.

People in families that have rare inherited conditions are at a higher risk of developing colon cancer. If a person has a family history of colon cancer, it doubles the risk of developing

1. The risk increases furthermore if a first degree relative has been diagnosed at a younger age with colon cancer. These rare inherited conditions include lynch syndrome and familial adenomatous polyposis. 

Lynch Syndrome (sometimes called Hereditary Non-Polyposis Colorectal Cancer or HNPCC):

So far, upto five genes have been discovered that lead to this type of colon cancer.  Mutations in the genes MSH2 and MLH1 are considered to be the primary mutations that cause HNPCC. 

Familial Adenomatous Polyposis (FAP):

So far, only one gene has been discovered that leads to this type of colon cancer. Individuals who inherit this gene mutation have a very strong chance of developing colon cancer after the age of 40. 

The genes that cause the above two types of colon cancer are easier to discover as they exert strong effects. 

If the patient is found to be carrying any of these genes, regular screening tests are recommended to allow for early detection and treatment of cancer. Since this type of cancer can develop at an early age, even children below the age of 18 are advised to undertake screening tests if their parent is known to be a carrier of such gene mutations.

Surgery:

This is the most common treatment for colon cancer and is called asurgical resection. In this procedure along with the affected part, part of the healthy colon or rectum and lymph nodes will be removed. Surgery is done by either of the three methods – open method, laparoscopic method and robotic method.

Chemotherapy:

It is the use of cytotoxic or anticancer drugs to kill cancer cells, and is often used as a treatment option for colon cancer

Targeted therapy:

This type of treatment blocks the growth and spread of cancer cells while limiting the damage that is done to healthy cells. The different types of targeted therapies include anti-angiogenesis therapy, epidermal growth factor receptor (EGFR) inhibitors and checkpoint Inhibitors

Radiation therapy:

Radiofrequency ablation (RFA) or cryoablation is used for the liver metastasis. In this procedure, high energy radio waves are used to kill tumours.

The thyroid gland is located in the front part of the neck and has two lobes. These lobes are located on either side of the windpipe and are joined by a thin strip of tissue.

The thyroid gland makes hormones necessary for growth, metabolism and development of the body.

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Thyroid cancer has been associated with several inherited conditions and family history. However, most people with thyroid cancer have no family history or inherited condition. Some of the hereditary thyroid cancers include:

Medullary thyroid cancer:

Two out of ten medullary thyroid carcinomas are due to inheritance of an abnormal gene and are called familial medullary thyroid carcinoma or FMTC. 

Familial nonmedullary thyroid carcinoma:

FMTC  is a familial cancer that occurs at a younger age and runs in families with involvement of genes on chromosome 1 and 19. FMTC along with other endocrine gland tumors are called MEN 2 (multiple endocrine neoplasia type 2) caused by mutations in a gene known as RET. 

These hereditary cancers develop during childhood and can spread early. The risk of developing medullary thyroid cancer is very high if FMTC or MEN 2 runs in the family.

 Familial adenomatous polyposis (FAP):

This  syndrome is characterized by thedevelopment of multiple colon polyps that increase the risk of colon cancer as well as thyroid cancer.

Cowden disease:

Defects in PTEN gene causes Cowden disease also called  multiple hamartoma syndrome and individuals with this syndrome face increased risk of thyroid conditions including thyroid cancer and cancers of the breast, uterus and others. 

Carney complex:

Mutations in a gene called PRKARIA can cause Carney complex syndrome associated with the development of hormone problems and benign tumors. The syndrome also increases the risk of thyroid cancers. 

If you suspect there is a family history of thyroid cancer, book an appointment with a cancer specialist who will guide you on screening, genetic testing and counselling. 

Staging of cancer helps doctors find out the extent to which the cancer has spread and determine the best course of treatment. 

 Surgery is the preferred treatment option for thyroid cancer where

doctors may choose to do lobectomy which involves removal of the cancerous lobe in the thyroid gland or thyroidectomy where the entire thyroid gland is removed. If the cancer is found to have spread to lymph nodes,  they are removed as well.

Radioiodine therapy uses a form of iodine to destroy cancer cells in the thyroid gland. As only the thyroid gland can absorb iodine the damage is limited to thyroid cells with no effect on other organs. 

Early detection is the only way to cure hereditary cancers. If you or your loved one has a known family history of any type of cancer, it is important to consult a top cancer specialist in your area to get the required screening and counseling.