Pediatric Annals


Childhood Exposures and Risk of Malignancy in Adulthood

Vivian Y. Chang, MD, MS; Tom B. Davidson, MD


Pediatricians have significant roles in preventive health care, and understanding how various exposures during childhood can have long-lasting effects on cancer risk is critical in promoting future health. With the exception of rare genetic syndromes conferring increased cancer susceptibility, most cancers are considered idiopathic and may be influenced by modifiable exposures and risks. This review aims to serve as a brief overview of a subset of known exposures during childhood that have been associated with an increased risk of malignancy in adulthood, including the effects of radiation, chemotherapy, pesticides, nutrition, puberty, and infection. [Pediatr Ann. 2015;44(11):e270–e273.]


Pediatricians have significant roles in preventive health care, and understanding how various exposures during childhood can have long-lasting effects on cancer risk is critical in promoting future health. With the exception of rare genetic syndromes conferring increased cancer susceptibility, most cancers are considered idiopathic and may be influenced by modifiable exposures and risks. This review aims to serve as a brief overview of a subset of known exposures during childhood that have been associated with an increased risk of malignancy in adulthood, including the effects of radiation, chemotherapy, pesticides, nutrition, puberty, and infection. [Pediatr Ann. 2015;44(11):e270–e273.]

Although cancer is the second leading cause of death in the United States, our understanding of the origins of cancer remains incomplete.1 The vast majority of cancers are thought to be idiopathic and may be attributable to environmental exposures, lifestyle factors, and infections. This article is therefore intended to serve as a brief overview for the general pediatrician of exposures during childhood that have been associated with adult-onset malignancy.

Effect of Radiation

Studies of people exposed to nuclear accidents and atomic bombings provide strong evidence for the link between radiation and development of cancer. Children who had been exposed to atomic bombings in Japan had an increased risk predominantly of solid tumors and adult-onset leukemias. Leukemias were the first late effect to be recognized, and risk appears to peak shortly after exposure.2 Different solid cancers are associated with varying risk factors, depending on gender, age at exposure, and radiation dose, and risk for the development of malignancy may continue for decades.3

Cancer risk due to radiation exposure from radiologic examinations is an area of active study. It is generally accepted that radiologic examinations can be separated into two risk groups: higher-dose examinations, such as computed tomography scans (organ dose of 5–100 mGy), and lower-dose examinations, such as conventional X-rays (organ dose of <0.5 mGy). There have been attempts to extrapolate risk to patients exposed to higher-dose radiologic examinations from those exposed to low-dose radiation from atomic bombings of World War II. Although it is difficult to quantify exact radiation dose exposures for comparison, most studies conclude there is a small risk of increased cancer. For lower-dose radiologic examinations, there is a paucity of data but it is generally accepted that the risk is minimal to none.4

Radiofrequency electromagnetic fields were classified as a potential carcinogen by the International Agency for Research on Cancer (IARC) in 2011 due to early epidemiologic studies linking cell phone use and risk of gliomas and acoustic neuromas.5 Since then, there have been additional reports of meningioma risk associated with cell phone use.6,7 However, in vivo laboratory studies have not confirmed the link between cancer and radiofrequency exposure.8

The link between ultraviolet (UV) radiation and skin cancer is well established, and the amount of UV radiation exposure appears to be increasing annually due to changes in atmospheric content.9 There are ongoing studies attempting to define the exposure duration and type to the different subtypes of skin cancer, but a single blistering sunburn during childhood results in a multivariable adjusted relative risk of melanoma of 1.3.10

Therapeutic ionizing radiation is a standard component of many pediatric cancer treatments for central nervous system tumors, Hodgkin's lymphoma, solid tumors, and as part of preconditioning regimens for hematopoietic stem cell transplant (HSCT). The risk of secondary malignancies (SMs) after radiation therapy is well recognized and usually occurs 10 to 15 years after exposure.11 The most common SMs seen in pediatric cancer survivors include non-melanoma skin cancer, breast and thyroid carcinoma, bone tumors, gliomas, and meningiomas; the location usually corresponds to areas of previous irradiation.11

Effect of Chemotherapy

Chemotherapy refers to drugs or medicine used to treat cancer. The most serious side effect affecting chemotherapy treatment is the development of a secondary cancer, which is defined as a new cancer that is distinct from the original disease and may occur anywhere from 2 months after the completion of chemotherapy treatment to decades later.12,13

Secondary acute myeloid leukemia (s-AML) is the most common chemotherapy-associated secondary cancer. Children who were treated with alkylating agents and topoisomerase II inhibitors for their initial malignancies have the highest probability of developing s-AML in a dose-dependent manner.14 The most common alkylating agents include cyclophosphamide, ifosfamide, busulfan, dacarbazine, nitrosoureas, and cisplatin, which are used in current treatments for leukemias, solid tumors, and preconditioning regimens for HSCT. Alkylating agent–related s-AML is often preceded by myelodysplastic syndrome, which usually occurs 5 to 7 years after completion of initial therapy.15 Topoisomerase II inhibitors, such as anthracyclines, etoposide, and tenoposide, are associated with s-AML that develops earlier, usually occurring 2 to 3 years after the completion of chemotherapy. Unlike alkylating agents, studies have shown that the dosing schedule of topoisomerase II agents, rather than the cumulative dose, is the crucial risk factor.16

Effect of Chemicals and Pesticides

Pesticides are a large group of chemicals intended to target pests, and can be found in the environment, in food, and in household goods. Exposures to various pesticides have been most frequently linked to lung, prostate, and blood cancers.17,18 However, arsenic as an active ingredient in pesticides is the only confirmed carcinogen identified as such by the IARC19 and US government agencies.

Organic foods usually contain less pesticide residue, and although consumers believe them to be healthier, nutrition content has actually been found to be the same.20 In one large prospective study in the United Kingdom, consumption of organic food did not affect the incidence of cancer in adult women.20

Bisphenol A (BPA) is an endocrine-disrupting chemical found in plastics, can linings, paper receipts, and other common household goods. To date, there have been no human studies linking adverse health effects with BPA exposure. However, there are animal and cell culture studies that show BPA affects pathways that regulate cell growth and proliferation through epigenetic effects, suggesting a link to cancer.21,22

Effect of Nutrition

One underlying biologic mechanism of the long-lasting effect of nutrition on later health may be mediated by a specific C-phosphate-G (CpG) island methylation phenotype (CIMP), which is thought to regulate gene activity by silencing areas that are usually sites of transcription initiation. A population in the Netherlands that survived a period of famine during adolescence and young adulthood was found to have a decreased risk of colorectal cancer corresponding to a persistent CIMP signature.23 Another study evaluating the effect of calorie restriction in patients with anorexia nervosa demonstrated that there was a decreased risk of breast cancer.24

Higher body mass index during childhood and adolescence has been linked to multiple adult-onset solid tumors, such as brain tumors, lymphoma, and colorectal, pancreatic, ovarian, and endometrial cancers.25 Using height as a surrogate for high energy intake during childhood, tall stature was associated with increased risk of testicular germ cell tumor.26 Therefore, nutrition- or environment-induced increases in growth, whether reflected by weight or height, seem to be associated with increased cancer risk, similar to congenital overgrowth syndromes that are also accompanied by increased cancer risk.

Effect of Puberty

Timing of puberty and first pregnancy are known to affect risk of breast cancer.27 Younger age at menarche corresponds with younger age at the start of breast development and younger age of pubertal growth spurt. These factors together contribute to increased risk of breast cancer.28–30 Conversely, younger age at first pregnancy is associated with decreased risk of breast cancer. This is thought to be due to the permanent differentiation of mammary tissue that occurs during pregnancy, which may make mammary cells less susceptible to environmental insults.28,31

Use of oral contraceptive pills (OCPs) during adolescence and risk of cancer is dependent on dose. Before 1975 when OCPs contained higher doses, there appeared to be a slight increased risk of breast cancer, particularly in patients with underlying genetic susceptibility.32 However, there have now been studies showing that modern OCPs do not increase risk of breast cancer even in patients with underlying genetic susceptibility, and may even decrease risk of ovarian cancer.33

Effect of Infection

Epstein-Barr virus (EBV) is a nearly ubiquitous herpes virus that infects B-lymphocytes and causes a spectrum of disorders from mononucleosis to lymphoproliferative disease to lymphoma.34 EBV is transmitted via secretions such as saliva, and in the United States about 50% of 5-year-old children have evidence of previous infection, and by adulthood 90% have been infected. Many children who are infected in early childhood are asymptomatic or the symptoms are similar to other self-limited viral infections in childhood. Human T-lymphotropic virus type I, which is endemic in certain parts of the world, causes adult T-cell leukemia lymphoma.35 Japan has the highest prevalence in the general population, although in certain countries, high-risk populations such as immigrants and intravenous drug users can also have high rates of infection. Infection with HIV during childhood can lead to cancer, usually as an AIDS-defining event such as Kaposi's sarcoma and non-Hodgkin's lymphoma, as well as non-AIDS defining events such as leukemia or other solid tumors.36 There have also been major public health successes with the introduction of vaccines for hepatitis B and human papillomavirus reducing the risks of hepatocellular carcinoma and cervical cancer, respectively.37


Although cancer risk assessment and prevention involve a complex interplay between genetics and exposures, general pediatricians can have a critical role in educating and limiting known impacts during childhood that can lead to a decreased risk of adult malignancy.


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Vivian Y. Chang, MD, MS, is an Assistant Professor of Pediatrics, University of California, Los Angeles, David Geffen School of Medicine, Children's Discovery and Innovation Institute, Mattel Children's Hospital, and Jonsson Comprehensive Cancer Center. Tom B. Davidson, MD, is an Assistant Professor of Pediatrics, University of California, Los Angeles, David Geffen School of Medicine, Children's Discovery and Innovation Institute, Mattel Children's Hospital, and Jonsson Comprehensive Cancer Center.

Address correspondence to Vivian Y. Chang, MD, MS, 10833 Le Conte Avenue, MDCC A2-410, Los Angeles, CA 90095; email:

Disclosure: The authors have no relevant financial relationships to disclose.


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