Risk Factors for Getting Cancer More Than Once

Improved healthcare and increased accessibility of modern diagnostic and treatment methods have resulted in prolonged life expectancy in the general population and particularly in people with cancer. However, some cancer survivors get a second cancer diagnosis during their lifetime. This article reviews the reasons why this could happen and describes a case of successful treatment of multiple cancers in the same person.

Key takeaways:

With improved cancer diagnostics and treatment, the cure rate of cancer has reached approximately 80% in children and almost 70% in adults. As the population of cancer survivors increases (about 18 million living in the U.S.), more is being learned about their long-term health issues. One such issue is a higher risk of getting second cancer during the lifetime.

Factors increasing the risk of multiple cancers

Indeed, about 1 in 6 people diagnosed with cancer receive this diagnosis for the second time, and the proportion of second cancer has doubled in the last three decades. Previous cancer treatments, unhealthy lifestyles, concomitant diseases, and genetic predisposition — all increase the risk of developing multiple cancers.

Previous cancer treatments

Some types of chemotherapy and radiation therapy, especially when administered at high doses and for prolonged periods, are associated with an increased risk of developing a second cancer. The most common cancer types which occur as a consequence of previous cancer treatment are myelodysplastic syndrome and acute myeloid leukemia (types of blood cancer).

Both chemotherapy and radiation therapy act by hampering cancer cell division processes. Since cancer cells divide more actively compared with healthy cells, the effect on cancer cells is more pronounced. However, healthy cells are also exposed to some DNA damage which tends to accumulate over time to the extent that cellular DNA repair mechanisms are not able to handle. This may eventually lead to a secondary cancerous transformation.

Lifestyle choices

Certain lifestyle factors such as smoking, excess alcohol intake, and obesity are well-known risk factors for the development of many cancers. For instance, smoking is associated not only with lung cancer but also with cancer of the oral cavity, pharynx, esophagus, stomach, liver, pancreas, and others. Of note, the risks associated with exposure to several adverse lifestyle habits may be much higher than those for either risk factor alone.

Adverse lifestyle factors, like smoking, may enhance the effect of chemotherapy or radiation therapy on cancer risk. In women with breast cancer administered radiation therapy, the development of second lung cancer was restricted to smokers. Therefore, if adverse lifestyle factors are not eliminated, the risk of developing second cancer increases.

Concomitant diseases

Concomitant diseases, especially those affecting endocrine and immune systems, increase the risk of developing several cancers. Some cancers, including breast, ovarian, uterine, and prostate cancer are dependent on sex hormones. Thus, states with hormonal disbalance may influence the development of several cancers in different organs of the reproductive system.

Since immunity plays an important role in cancer surveillance and eradication, inborn or acquired immunodeficiencies may elevate the risk of certain cancers. For instance, AIDS is associated with an increased risk of non-Hodgkin lymphoma (a type of blood cancer), Kaposi sarcoma (a type of cancer that starts in the lining of blood and lymphatic vessels), and skin cancer. Moreover, an increased risk of some infections (e.g., human papillomavirus) in immunocompromised people may also lead to the development of multiple cancers.

Genetic predisposition

Up to 10% of cancers develop through inherited mutations. Frequently these mutations occur in the genes that protect against the damage of genetic material and thus increase susceptibility to several cancers. For instance, inherited mutations in the BRCA1 and BRCA2 genes raise the risk of breast, ovarian, and pancreatic cancer in women and prostate cancer in men.

Besides inherited mutations, some acquired genetic abnormalities may raise the risk of treatment-associated cancer. Chromosomal abnormalities and mutation of the TP53 gene which regulates cell division are often encountered in treatment-associated myelodysplastic syndrome which may develop years after radiation therapy or chemotherapy.

Case study: A woman who has survived 12 tumors

An article in Science Advances presented a case of a woman who had survived 12 tumors including 5 malignant cancers by the age of 36 years. Due to mutated MAD1L1 gene copies which she inherited from each of the parents, 30% to 40% of her blood cells have too many or too few chromosomes, a condition known as genomic instability. Mutations in both MAD1L1 copies have never been encountered in a human before. In mice, embryos with such mutations usually die before birth.

The woman was diagnosed with embryonal rhabdomyosarcoma (a type of muscle cancer) at two years, cervical cancer at 15 years, a benign parotid gland tumor at 20 years, and a malignant parotid gland tumor at 21 years. During several next years, she was operated on for skin lesions, a benign breast tumor, a benign tumor of the hair follicle, and thyroid nodules. Several benign and malignant formations in the colon and rectum were also removed.

Along with increased susceptibility to cancer, her body developed enhanced immune responses, including stronger inflammatory reactions and expansion of certain lymphocyte clones acting against tumor cells. However, it is not known whether this could have influenced her cancer outcomes.

How to reduce the multiple cancer risk

Not all risks of multiple cancers can be controlled. However, since lifestyle plays a role in second cancer development, adopting a healthier lifestyle (e.g., quitting smoking or alcohol use) may have a positive influence.

Although second cancer is often harder to treat than primary cancer, early detection may improve treatment outcomes. Therefore, even after completing a required period of monitoring for the cancer recurrence, regular visits to a general practitioner at least once a year are judicious. Based on medical history, monitoring of common health indices as well as screening for skin lesions, colorectal formations, prostate, gynecological, breast cancer, and certain other conditions may be recommended.

To conclude, it is important for cancer survivors to be attentive to their health, maintain a healthy lifestyle and have regular check-ups. These measures will help to optimize the chances of second cancers’ control should they develop.



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