Understanding the Hereditary Risk Factors for Cancer - Dr lakhan Kashyap

Cancer is due to the unregulated growth of abnormal tissue which invades normal structures and spreads across the body. The irreversible changes in genes regulating growth of normal tissue leads to the development of cancer. These changes in the gene can be sporadic i.e. brought by increasing age, environmental and lifestyle factors.

Occasionally, these changes can be germline i.e. the abnormal genes are inherited and lead to hereditary cancer syndromes. Hereditary risk factors for cancer refer to genetic mutations or variations that increase the likelihood of developing certain types of cancer. These mutations can be passed down from parents to their offspring and can significantly impact an individual's cancer risk.

Most cancers develop without a strong family history and aren't passed down through generations. In these cases, the cancer-causing mutations arise within the tumour itself, after birth. These mutations might be triggered by environmental factors, hormones, or even random errors during cell division. Since, they happen after birth, they can't be inherited, making these cancers "sporadic."

Hereditary cancer syndromes comprise less than 10% of overall cancer incidence, for example around 5% of breast and colon cancers are hereditary. The common cancers which can present as hereditary cancer syndromes are breast cancer, ovarian cancer, colon cancer, prostate cancer and pancreatic cancer.

There are several critical indicators which point towards hereditary cancer syndromes such as:

• Early age of onset (e.g. < 45 years for breast, colon or uterine cancer)
• Multiple family members on same side of pedigree with same cancer
• Multiple cancers in one individual (e.g. breast and ovarian cancer, colon and uterine cancer)
• Multiple polyps (>10) in colon
• Clustering of cancers or benign changes in an individual or family that is associated with hereditary cancer syndromes (e.g. FAP syndrome: Colon cancer, colon polyps and desmoid tumors)
• Presence of certain tumors – male breast cancer, adrenocortical cancer, pheochromocytoma, retinoblastoma
• Certain pathological subtypes of tumor- triple negative breast cancer, medullary thyroid cancer

Hereditary Cancer Syndromes: When Genes Raise Risk

Hereditary cancer syndromes are groups of cancers linked to specific gene mutations passed down through families. A well-known example is hereditary breast and ovarian cancer (HBOC), often caused by mutations in the BRCA1 and BRCA2 genes.

People with these mutations have a higher chance of developing breast, ovarian, and some other cancers. Similarly, Lynch syndrome, linked to mutations in DNA repair genes like MLH1 and MSH2, increases the risk of colorectal and other cancers.

How These Mutations Get Passed Down

The inheritance pattern of these cancer-linked mutations can vary. Some, like those in HBOC, follow an autosomal dominant pattern. This means inheriting just one mutated copy of the gene from either mom or dad is enough to raise your cancer risk.

Others, like Lynch syndrome, are more complex. Here, inheriting specific combinations of mutated genes from both parents can increase cancer risk.

Why knowing the hereditary risk factors is important?

Knowing the hereditary risk for cancer can have a few advantages. Firstly, individuals with identified genetic mutations can participate in specialised screening programs. Early detection through these programmes means catching cancer at a more treatable stage, significantly improving outcomes.

Furthermore, awareness of the genetic predisposition empowers patients to make informed decisions about preventive measures. This could involve proactive steps like prophylactic surgery or adopting healthier lifestyle choices to reduce the cancer risk.

Signs suggesting Hereditary Cancer

If one has concerns about the family history, be aware of these potential signs:

• Two or more relatives with the same type of cancer, on the same side of the family
• Several generations have been affected by cancer.
• Early ages of cancer diagnosis in family members
• Individuals with more than one primary cancer
• The occurrence of one family of cancers known to be genetically related (e.g., breast and ovarian cancer, or colon and uterine cancer)
• The presence of physical signs associated with hereditary cancer (e.g., moles and melanoma, or polyps and colon cancer)
• Certain rare types of cancer

It is important to note that while genetic variables play a role in determining cancer risk, they are not the only ones. Environmental factors, such as exposure to carcinogens like tobacco smoke or ultraviolet radiation, also play significant roles in cancer development.

Genetic counselling and testing are must

For those with a family history of cancer or concerns about their hereditary risk, genetic counselling and testing can be invaluable. These services offer personalised risk assessments and tailored screening recommendations and empower individuals to make informed decisions about managing their cancer risk.

Individuals who are predisposed to hereditary cancer syndromes should undergo genetic counselling and testing to identify variants of genes responsible for these syndromes. Those individuals who are found positive for these pathogenic variants of the gene should consult the oncologist, as the risk of having cancer in these individuals can be as high as 90%.

The cancers associated with these syndromes are curable. The oncologist can guide the appropriate diagnostic and therapeutic intervention to identify these cancers at early stages where they can be completely cured.

It's important to understand inherited risk factors, which are specific gene mutations that increase a person's susceptibility to certain cancers. It highlights the significant connection between genetics and cancer prevention and treatment by enabling personalised cancer risk identification and control.

It's important to talk to the doctor about hereditary cancer risk and explore options like genetic testing and preventive measures. Early detection is key to successful cancer treatment.