The Rising Incidence of Second Cancers: Patterns of Occurrence and Identification of Risk Factors for Children and Adults

Morton, Lindsay M.; Onel, Kenan; Curtis, Rochelle E.; Hungate, Eric; Armstrong, Gregory T.

doi:10.14694/edbook_am.2014.34.e57

Cited by 172 publications

(160 citation statements)

References 59 publications

(72 reference statements)

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“…27). Approximately 17% to 19% of cancers diagnosed today have a previous history of a primary malignancy (27). The general risk of developing SMNs is thought to be higher in survivors of childhood cancers than adult cancers.…”

Section: Ramifications Of Distinct Dna Damage Thresholds In Human Canmentioning

confidence: 99%

DNA Damage in Cancer Therapeutics: A Boon or a Curse?

2015

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Millions of DNA-damaging lesions occur every day in each cell of our bodies due to various stresses. The failure to detect and accurately repair these lesions can give rise to cells with high levels of endogenous DNA damage, deleterious mutations, or genomic aberrations. Such genomic instability can lead to the activation of specific signaling pathways, including the DNA damage response (DDR) pathway. Constitutive activation of DDR proteins has been observed in human tumor specimens from different cancer stages, including precancerous and metastatic cancers, although not in normal tissues. The tumor-suppressive role of DDR activity during the premalignant stage has been studied, and strong evidence is emerging for an oncogenic role for DDR proteins such as DNA-PK and CHK1 during the later stages of tumor development. However, the majority of current cancer therapies induce DNA damage, potentially exacerbating protumorigenic genomic instability and enabling the development of resistance. Therefore, elucidating the molecular basis of DNA damagemediated genomic instability and its role in tumorigenesis is critical. Finally, I discuss the potential existence of distinct DNA damage thresholds at various stages of tumorigenesis and what the ramifications of such thresholds would be, including the ambiguous role of the DDR pathway in human cancers, therapyinduced malignancies, and enhanced therapies.

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Section: Ramifications Of Distinct Dna Damage Thresholds In Human Canmentioning

confidence: 99%

DNA Damage in Cancer Therapeutics: A Boon or a Curse?

2015

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“…12 One also needs to consider that lifestyle and environmental exposures also play a role in SPN risk and these tend to accumulate with life. 4 Finally, we also focused on the potential influence of the treatment modalities for uveal melanoma on the risk of SPN. In our cohort, SIR calculations according to previous radiotherapy revealed that, after excluding cases coded as a second UM, eyes that had received this treatment did not present a significantly increased all-sites risk as compared to the reference population.…”

Section: Study Populationmentioning

confidence: 99%

“…Additionally, melanoma metastases can histologically mimic some soft tissue tumors, which can lead to misdiagnosis. Moreover, the SEER database does not collect data on genetic and lifestyle risk factors (eg, smoking) that are currently known to influence the risk of SPN 4 and would be interesting to analyze. In assessing the incidence of multiple types of SPN, multiple tests were completed that could have led to false-positive associations.…”

Section: Study Populationmentioning

confidence: 99%

“…[1][2][3] It is well established that cancer survivors are especially prone to developing independent second primary neoplasms (SPNs) and that their characteristics vary according to the site of the first primary tumor. 4,5 This increased risk is recognized to have multifactorial causes. Lifestyle and environmental exposures, such as smoking 6 and alcohol consumption, 7 have been implicated.…”

mentioning

confidence: 99%

“…15,16 The suggested underlying factors for SPN risk after this treatment include the doses and modalities applied, as well as the volume of tissue irradiated. 4,5 This risk is most pronounced in the organs within the irradiated fields 13,14 but has also been described in sites not directly exposed to radiation. 17,18 A potential explanation includes ''bystander response-like phenomena, '' 19,20 through the release of blood cells and mediators from the irradiated fields that can induce genomic instability and cell transformation.…”

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confidence: 99%

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Second Primary Neoplasms in Patients With Uveal Melanoma: A SEER Database Analysis

Bartosch

Mondim

Healy

et al. 2016

American Journal of Ophthalmology

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PURPOSE: To determine the risk of second primary neoplasms (SPNs) in subjects previously diagnosed with uveal melanoma (UM), including an analysis on whether radiotherapy is a risk factor to develop these SPNs.DESIGN: Retrospective cohort study. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) 9 database, we identified patients diagnosed with UM as their first malignancy between 1973 and 2011 (n [ 3976). We obtained standardized incidence ratios (SIR) and excess absolute risks of SPNs on patients with UM compared to a reference population. Multivariate Cox regression models were used to evaluate the effect of radiotherapy in SPN risk.RESULTS: Sixteen percent (n [ 641) of the patients developed SPNs during a median follow-up of 83 months (range, 1-463 months). This represented an 11% excess risk compared to the reference population, mainly owing to a significantly increased risk of skin melanomas (SIR [ 2.93, 95% CI: 2.23-3.78) and kidney tumors (SIR [ 1.91, 95% CI: 1.27-2.76), primarily in those diagnosed between 30 and 59 years of age. The occurrence of second UM was also increased (SIR [ 16.90, 95% CI: 9.00-28.90), which likely includes recurrences misclassified as a second cancer. Radiotherapy was performed in 39% (n [ 1538) of the patients. Multivariate analysis revealed that this treatment was not an independent risk factor for SPNs (hazard ratio [ 1.06, 95% CI: 0.88-1.26, P [ .54).CONCLUSIONS: Patients with UM presented an 11% higher risk of SPNs compared to the reference population. Radiotherapy does not seem to be a risk factor. SPNs should be considered in the surveillance of UM. (Am J Ophthalmol 2016;165:54-64. Ó 2016 Elsevier Inc. All rights reserved.) P UBLISHED DATA ON SURVIVAL OF UVEAL MELAnoma demonstrate that more than half of the patients are long-term survivors. At 5 and 10 years, the survival rates range between 68%-82% and 57%-62%, respectively.

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Excess Body Weight and the Risk of Second Primary Cancers Among Cancer Survivors

Bodelon,

Sung,

Mitchell

et al. 2024

JAMA Netw Open

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ImportanceLittle is known about the causes of second primary cancers among individuals with a history of cancer. Descriptive studies have suggested that lifestyle factors, including excess body weight, may be important.ObjectiveTo investigate whether excess body weight is associated with the risk of a second primary malignant neoplasm among cancer survivors.Design, Setting, and ParticipantsThis cohort study of adults in 21 states in the US used data from the Cancer Prevention Study II Nutrition cohort, a large prospective study that invited participants to respond to a survey in 1992 and biennial surveys starting in 1997, and who were followed-up through 2017. Eligible participants included those who received a diagnosis of a first primary nonmetastatic invasive cancer between 1992 and 2015. Data analysis occurred from September 2023 to March 2024.ExposureBody mass index (BMI), computed from self-reported height and weight at the time of the first primary cancer diagnosis (mean [SD] years to diagnosis, 1.7 [1.5] years).Main Outcome and MeasuresMain outcomes included a second primary cancer or an obesity-related second cancer. Cancer diagnoses were reported on biennial surveys and verified through medical record abstraction or linkage with state cancer registries.ResultsThis cohort included 26 894 participants who received a diagnosis of a first nonmetastatic primary cancer (mean [SD] age at first cancer diagnosis, 72.2 [6.5] years; 15 920 male [59.2%]). At the time of first diagnosis, 11 497 participants (42.8%) had overweight and 4684 (17.2%) had obesity. During a median (IQR) follow-up time of 7.9 (3.4-13.6) years, 3749 (13.9%) participants received a diagnosis of a second primary cancer, of which 1243 (33.2%) were obesity-related second primary cancers. Compared with cancer survivors whose BMI was in the normal range (18.5 to &lt;25), there was 15% increased risk of any second primary cancer for those who had overweight (25 to &lt;30; adjusted hazard ratio [aHR], 1.15; 95% CI, 1.07-1.25) and a 34% increased risk for those who had obesity (BMI ≥30; aHR, 1.34; 95% CI, 1.21-1.48), with greater risk for obesity-related second primary cancers, including a 40% increased risk for those with overweight (aHR, 1.40; 95% CI, 1.22,-1.61) and a 78% increased risk for those with obesity (aHR, 1.78; 95% CI, 1.51-2.11).Conclusions and RelevanceIn this cohort study of older survivors of nonmetastatic cancer, those who had overweight or obesity at the time of their first cancer diagnosis were at higher risk of developing a second cancer, especially an obesity-related second cancer. Given the high prevalence of overweight and obesity among cancer survivors, it is important to promote survivorship care guidelines recommending weight management and increase awareness of second cancers among physicians and cancer survivors.

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The Rising Incidence of Second Cancers: Patterns of Occurrence and Identification of Risk Factors for Children and Adults

Cited by 172 publications

References 59 publications

DNA Damage in Cancer Therapeutics: A Boon or a Curse?

DNA Damage in Cancer Therapeutics: A Boon or a Curse?

Second Primary Neoplasms in Patients With Uveal Melanoma: A SEER Database Analysis

Excess Body Weight and the Risk of Second Primary Cancers Among Cancer Survivors

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