Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study

Signorello, Lisa B.; Mulvihill, John J.; Green, Daniel M.; Munro, Heather M.; Stovall, Marilyn; Weathers, Rita; Mertens, Ann C.; Whitton, John; Robison, Leslie L.; Boice, John D.

doi:10.1200/jco.2011.37.2938

Cited by 135 publications

(106 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…14 Most studies report no chromosomal abnormalities, [20][21][22][23][24] malformations, 21,24-28 congenital defects 21 or cancer 29,30 in offspring of cancer survivors, with the exceptions of Dalberg et al 15 who noted an increased risk of malformation among women who conceived after treatment for breast cancer, Winther et al 28 who noted a small (not significantly increased) risk of malformations in children with a parent who received irradiation for childhood cancer and Stahl et al 27 who observed statistically significant but modestly increased risk of major congenital abnormalities among offspring of males with a history of cancer. In accordance with these previous publications, we observed an increased mortality risk in offspring of survivors of hematological cancer, a substantial part of whom will have received radiation therapy for (non) Hodgkin lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Mortality among offspring of women diagnosed with cancer: A population‐based cohort study

Verkooijen

Ang

Liu

et al. 2012

Intl Journal of Cancer

View full text Add to dashboard Cite

One in five cancers in women is diagnosed prior to and during a woman's fertile years. Our study evaluates mortality risks in offspring of mothers with history of cancer. From the Swedish Multi-generation Register and the Cancer Register, we identified all 174,893 children whose mother had been diagnosed with cancer between 1958 and 2001. We categorized offspring into those born before (>1 year before), around (within 1 year before and after diagnosis) and after (>1 year after) their mother's cancer diagnosis and compared their risks of death (standardized mortality ratios, SMRs) and causes of death to the background population. Overall, offspring of mothers diagnosed with cancer had no increased mortality risk (SMR, 1.00; 95% confidence interval [CI], 0.97-1.03). Increased mortality risks were found in offspring of mothers with tobacco-related cancers (head and neck, thoracic and cervical) (SMR, 1.23; 95% CI, 1.13-1.33), in children born around their mother's diagnosis (SMR, 1.66; 95% CI, 1.25-2.13) and in children born after their mother's hematopoietic cancer diagnosis (SMR, 2.07; 95% CI, 1.10-3.35). Compared to the background population, children born around their mother's diagnosis were more likely to die of congenital and perinatal conditions. Overall, offspring of women diagnosed with cancer were not at increased risk of death, except for certain subgroups. Timing of pregnancy in relation to diagnosis and cancer site modifies mortality risks in the offspring.Eighteen percent of female cancers are diagnosed prior to and during a woman's fertile years.1 About one in 1,000 pregnancies is complicated by a cancer diagnosis 2 and substantial proportion of cancer survivors give birth after their diagnosis (unpublished data). Pregnancy during or after a malignancy has repeatedly been shown not to affect maternal prognosis.3-5 However, exposure to (the effects of) diagnostic investigations, radiation therapy and systemic treatment before and around the time of birth may have adverse effects on the child. 3,4,[6][7][8] Population-based estimates on the outcome of offspring of cancer survivors are lacking. Most studies on childbirth after cancer are hampered by small numbers, as pregnancy during and after cancer is a relatively rare event. As such, these studies are underpowered to pick up small, but real increases in mortality risks in the offspring. Although small effects may not be so relevant on an individual patient level, small increases in risk of complications or death in offspring of cancer patients are important from a public health perspective, especially in the light of the growing number of young cancer survivors and improvement in fertility preservation techniques.With our study, using data of the large population-based Swedish Multi-Generation Registry including over three million families and eleven million individuals, we assess mortality risks in offspring of women with a history of cancer in relation to timing of birth and cancer site. MethodsWe linked data from the Multi-Generation Register (incl...

show abstract

Section: Discussionmentioning

confidence: 99%

Mortality among offspring of women diagnosed with cancer: A population‐based cohort study

Verkooijen

Ang

Liu

et al. 2012

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…A refined analysis yielded similar negative results and omitted the controls, but sought a dose-response effect over a wide range of estimated doses of ionizing radiation to the survivors' gonads, as well as semi-quantitative estimates of their doses of alklyating agents. The mean dose of radiation was 126 cGy to ovaries and 26 cGy to the testes (Signorello et al 2012).…”

Section: Pre-conceptual Exposure To Cancer Therapymentioning

confidence: 99%

Preconception exposure to mutagens: medical and other exposures to radiation and chemicals

Mulvihill

2012

J Community Genet

Self Cite

View full text Add to dashboard Cite

Contrary to intuition, no environmental exposure has been proved to cause human germ line mutations that manifest as heritable disease in the offspring, not among the children born to survivors of the American atomic bombs in Japan nor in survivors of cancer in childhood, adolescence, or young adulthood who receive intensive chemotherapy, radiotherapy, or both. Even the smallest of recent case series had sufficient statistical power to exclude, with the usual assumptions, an increase as small as 20 % over baseline rates. One positive epidemiologic study of a localized epidemic of Down syndrome in Hungary found an association with periconceptual exposure to a pesticide used in fish farming, trichlorfon. Current population and occupational guidelines to protect against genetic effects of ionizing radiation should continue, with the understanding they are based on extrapolations from mouse experiments and mostly on males. Presently, pre-conceptual counseling for possible germ cell mutation due to the environment can be very reassuring, at least based on, in a sense, the worst-case exposures of cancer survivors. Prudence demands further study. Future work will address the issue with total genomic sequencing and epigenomic analysis.

show abstract

“…The included studies were published between 1999 and 2014, and all of them were cohort studies [4,[6][7][8][9][10][11][12][13][14][15][16][17][18]. A total of 10,717 women with radiation therapy and 11,128 women without radiation therapy from 13 studies were evaluated [4, 6-15, 17, 18].…”

Section: Resultsmentioning

confidence: 99%

“…In fertility factors, 5 studies were described about infertility [6,9.12,14, 18], 2 studies were based on AMH values [4,17], 2 studies on AOF [10,16], 3 studies on stillbirth or neonatal death [7,8,13], 2 studies on spontaneous abortion [7,12], 2 studies on congenital anomaly [7,15], 2 studies on low birth weight [7,11] and 1 study on preterm birth [11]. In radiation therapy methods, 4 studies were performed in radiation therapy without specific description [10,12,16,2], 2 studies on abd-pelvic radiation [6,7], 2 studies on ovarian radiation [8,15] and each of the 6 last studies were performed on pelvic radiation [4], abdominal or total body radiation [17], hypothalamic or pituitary radiation [14], nasopharyngeal radium irradiation [9], uterus radiation [11], uterus and ovarian radiation [13].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study

Gao

Liang

Qiu

2015

J Assist Reprod Genet

View full text Add to dashboard Cite

Background and aims Many epidemiological studies have revealed a positive correlation between medical radiation exposure and the reproductive health in female childhood cancer survivors. However, because of variations in the samples size, such studies showed partly inconsistent conclusions. The aim of this meta-analysis was to clarify the association between radiotherapy and the risk of reproductive health impairment for female who survived from childhood cancer. Methods Fourteen cohort studies involving childhood radiotherapy were selected as the exposure of interest and the impaired reproductive health condition during the childbearing age as the outcome. Among meta-analysis of observational studies found in Pubmed and Embase from 1900 to 2014, we evaluated those relevant observational studies which surveyed the association of medical radiation and reproductive health in female childhood cancer survivors. Review Manager 5.2 and STATA 12.0 software were used to perform the metaanalysis. Study-specific estimations for each outcome were combined into a pooled relative risk (RR) with 95 % confidence interval (CI) by a meta-analytic approach.Results Based on a random-effects meta-analysis, significant association between infertility (RR=1.28, 95 % CI=1.16-1.42), acute ovarian failure (AOF) (RR=9.51, 95 % CI=5.03-17.96), low level of anti mullerian hormone (AMH) (<1 ng/mL) (RR=14.79, 95 % CI=3.36-66.64), stillbirth (RR=1.19, 95 % CI=1.02-1.39) and low birth weight (RR=2.22, 95 % CI= 1.55-3.17) were identified. Conversely, no significant results were found in abortion and congenital malformations. Conclusions To the best of our knowledge, this is the first meta-analysis assessing the effect of medical radiation on female childhood cancer survivors' reproductive capability and pregnancy outcomes. Although there were some limitations, our meta-analysis further supported that radiotherapy was a risk factor for reproductive health problems of female who survived from childhood cancer.

show abstract

Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study

Cited by 135 publications

References 33 publications

Mortality among offspring of women diagnosed with cancer: A population‐based cohort study

Mortality among offspring of women diagnosed with cancer: A population‐based cohort study

Preconception exposure to mutagens: medical and other exposures to radiation and chemicals

Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study

Contact Info

Product

Resources

About