Risk Of Cancer In Offspring Research Articles

In utero exposure to methyl diet and epigenetic modification of breast cancer risk in offspring

Lipotropic nutrients contain methyl groups and affect DNA methylation, an epigenetic mechanism controlling expression of genes involved in cell growth and metabolism. Fuller differentiation of mammary gland during the first pregnancy has a protective effect against breast cancer. We studied a correlation between methyl metabolism-directed and pregnancy-related epigenetic modification of mammary gland development and reduction of breast cancer risk in female offspring. Female Sprague-Dawley rats were fed either control or lipotrope diet during pregnancy and lactation. At weaning, mammary tissues were analyzed for global DNA methylation level by quantitative DNA methylation and for expression of genes involved in mammary differentiation by real-time PCR. Half of the offspring were also used for the preceding purpose. Mammary cancer was induced in the remaining offspring by nitrosomethylurea protocol. The offspring in the lipotropic group showed a decrease in tumor incidence as compared to control diet group. Further, maternal lipotrope diet significantly reduced tumor volume (P<0.01) and tumor numbers (P<0.01) in offspring. However, there was no difference in global methylation level and gene expression in dams and offspring from each diet group. Our results suggest maternal methyl diet reduces chemically-induced mammary carcinogenesis in offspring. Supported by a US Department of Defense grant. Grant Funding Source: US Department of Defense

Reproductive Outcomes for Survivors of Childhood Cancer

Because of remarkable progress in therapy, long-term survival is expected for 80% of children and adolescents diagnosed with cancer. Infertility remains one of the most common and life-altering complications experienced by adults treated for cancer during childhood. Surgery, radiation, or chemotherapy that negatively affects any component of the hypothalamic-pituitary-gonadal axis may compromise reproductive outcomes in childhood cancer survivors. The risk of infertility is generally related to the tissues or organs involved in cancer and the specific type, dose, and combination of cytotoxic therapy. In addition to anticancer therapy, age at treatment, sex, and likely genetic factors influence the risk of permanent infertility. When possible, contemporary protocols limit cumulative doses of cytotoxic therapy in an effort to optimize reproductive potential. If sterilizing therapy is required for cancer control, then fertility preservation measures should be explored before initiation of therapy. For childhood cancer survivors who maintain fertility, health risks to offspring resulting from their cancer treatment are major concerns. Radiation affecting ovarian and uterine function has been linked to pregnancy complications, including spontaneous abortion, preterm labor, fetal malposition, and low birth weight. The risk of congenital malformations, genetic disorders, and cancer appears to be low, with the exception of cancer risk in offspring born to survivors with germline cancer-predisposing mutations. This review summarizes research about cancer treatment factors affecting fertility and pregnancy outcomes of childhood cancer survivors. The data presented should facilitate the delivery of preventive counseling and age- and sex-appropriate interventions to optimize reproductive outcomes in childhood cancer survivors.

Cancer Risk in Children and Young Adults Conceived by In Vitro Fertilization

Studies conducted so far have found no statistically significant increased risk for cancer among children who are born after in vitro fertilization (IVF). We followed 26,692 children who were born after IVF during the years 1982-2005 by using the Swedish Cancer Register and compared the number of children who had cancer and were born after IVF with children who were not conceived by IVF. Adjustment was made for year of birth. Maternal age, parity, smoking, subfertility, previous miscarriages, BMI, and multiple births did not significantly affect cancer risk in offspring. High birth weight, premature delivery, and the presence of respiratory diagnoses and low Apgar score were risk factors for cancer. We identified 53 cases of cancer in children who were born after IVF against 38 expected cases: 18 of them with hematologic cancer (15 of them acute lymphoblastic leukemia), 17 with eye or central nervous system tumors, and 12 with other solid cancers. There were 6 cases of Langerhans histiocytosis against 1.0 expected. The total cancer risk estimate was 1.42 (95% confidence interval: 1.09-1.87). We found a moderately increased risk for cancer in children who were conceived by IVF. Putative intermediary factors could be preterm birth and neonatal asphyxia.

Risk of cancer among children of cancer patients—a nationwide study in Finland

Cancer treatments have the potential to cause germline mutations that might increase the risk of cancer in the offspring of former cancer patients. This risk was evaluated in a population-based study of early onset cancer patients in Finland. Using the nationwide registry data, 26,331 children of pediatric and early onset cancer patients (diagnosed under age 35 between 1953 and 2004) were compared to 58,155 children of siblings. Cancer occurrence among the children was determined by linkage with the cancer registry, and the standardized incidence ratios (SIRs) were calculated comparing the observed number of cancers with that expected, based on rates in the general population of Finland. Among the 9,877 children born after their parent's diagnosis, cancer risk was increased (SIR 1.67; 95% CI 1.29-2.12). However, after removing those with hereditary cancer syndromes, this increase disappeared (SIR 1.03; 95% CI 0.74-1.40). The overall risk of cancer among the offspring of siblings (SIR 1.07; 95% CI 0.94-1.21) was the same as among the offspring of the patients with non hereditary cancer. Risk of cancer in offspring, born before their parents cancer diagnosis, was elevated (SIR 1.37, 95% CI 1.20-1.54), but removing hereditary syndromes resulted in a diminished and nonsignificant association (SIR 1.08, 95% CI 0.93-1.25). This study shows that offspring of cancer patients are not at an increased risk of cancer except when the patient has a cancer-predisposing syndrome. These findings are directly relevant to counseling cancer survivors with regard to family planning.

Children's exposure to diagnostic medical radiation and cancer risk: epidemiologic and dosimetric considerations.

While the etiology of most childhood cancers is largely unknown, epidemiologic studies have consistently found an association between exposure to medical radiation during pregnancy and risk of childhood cancer in offspring. The relation between early life diagnostic radiation exposure and occurrence of pediatric cancer risks is less clear. This review summarizes current and historical estimated doses for common diagnostic radiologic procedures as well as the epidemiologic literature on the role of maternal prenatal, children's postnatal and parental preconception diagnostic radiologic procedures on subsequent risk of childhood malignancies. Risk estimates are presented according to factors such as the year of birth of the child, trimester and medical indication for the procedure, and the number of films taken. The paper also discusses limitations of the methods employed in epidemiologic studies to assess pediatric cancer risks, the effects on clinical practice of the results reported from the epidemiologic studies, and clinical and public health policy implications of the findings. Gaps in understanding and additional research needs are identified. Important research priorities include nationwide surveys to estimate fetal and childhood radiation doses from common diagnostic procedures, and epidemiologic studies to quantify pediatric and lifetime cancer risks from prenatal and early childhood exposures to diagnostic radiography, CT, and fluoroscopically guided procedures.

Familial clustering of cancer at human papillomavirus‐associated sites according to the Swedish Family‐Cancer Database

Familial aggregation of cervical cancer has been demonstrated previously, however aggregation of other human papillomavirus-associated anogenital, upper aerodigestive tract and skin cancers has not been fully characterized. The Swedish Family-Cancer Database, which contains reliable data on cancer incidence and nuclear family linkages for all residents of Sweden between 1958 and 2004, was used to calculate standardized incidence ratios (SIR) and 95% confidence intervals for offspring site-specific cancer risks according to site-specific cancer in sibling and parental probands. Offspring cancer risk was significantly increased when either a sibling or parent was affected at the same site for penile squamous cell carcinoma (SCC, SIR = 7.54), cervical adenocarcinoma (AC, SIR = 2.31), vulvar SCC (SIR = 2.27), skin SCC (SIR = 2.14), rectal AC (SIR = 1.86), in situ cervical SCC (SIR = 1.80), invasive cervical SCC (SIR = 1.77) and upper aerodigestive tract SCC (SIR = 1.57). Significant aggregation on the order of 2-fold between anogenital cancers at different sites or histologies was also observed. In situ cervical SCC risk in offspring was strongly influenced by siblings affected with oropharyngeal SCC (SIR = 3.17) and tonsillar SCC (SIR = 1.84). Familial skin SCC was largely unassociated with anogenital or upper aerodigestive tract cancer risk in offspring. These data suggest that common host factors exist among individuals affected with anogenital and upper aerodigestive tract cancers.

Increased risk of cancer in the offspring of female electronics workers

There is limited evidence on the hypothesis that maternal occupational exposure near conception increases the risk of cancer in offspring. This study is to investigate whether women employed in an electronics factory increases childhood cancer among first live born singletons. We linked the databases of Birth Registration and Labor Insurance, and National Cancer Registry, which identified 40,647 female workers ever employed in this factory who gave 40,647 first live born singletons, and 47 of them developed cancers during 1979–2001. Mothers employed in this factory during their periconceptional periods (3 months before and after conception) were considered as exposed and compared with those not employed during the same periods. Poisson regression model was constructed to adjust for potential confounding by maternal age, education, sex, and year of birth. Based on 11 exposed cases, the rate ratio of all malignant neoplasms was increased to 2.26 [95% confidence interval (CI), 1.12–4.54] among children whose mothers worked in this factory during periconceptional periods. The RRs were associated with 6 years or less (RR = 3.05; 95% CI, 1.20–7.74) and 7–9 years (RR = 2.49; 95% CI, 1.26–4.94) of education compared with 10 years or more. An increased association was also found between childhood leukemia and exposed pregnancies (RR = 3.83; 95% CI, 1.17–12.55). Our study suggests that maternal occupation with potential exposure to organic solvents during periconception might increase risks of childhood cancers, especially for leukemia.

Association of maternal fat and alcohol intake with maternal and umbilical hormone levels and birth weight

High levels of estrogen during pregnancy have been hypothesized to increase the risk of breast cancer in offspring. Some studies have reported a positive association of estrogen level during pregnancy with fetal size, which has been linked to the subsequent risk of breast cancer in offspring. We examined whether maternal diet, including fat and alcohol intake, was associated with hormone levels during pregnancy, as well as with birth weight. The concentrations of estradiol, estriol, and testosterone were measured in the maternal serum and umbilical cord blood of 189 women during pregnancy and at delivery. Intakes of fat, alcohol, and other nutrients were assessed by 5-day diet records at approximately the 29th week of pregnancy before blood sampling. Intake of polyunsaturated fatty acids was moderately but significantly positively correlated with the umbilical cord estriol level (r = 0.17, P = 0.03) after controlling for covariates. The positive association between intake of polyunsaturated fatty acids and birth weight was of borderline significance (r = 0.14, P = 0.06). Intake of long-chain n-3 fatty acids was significantly inversely correlated with the umbilical cord estradiol and testosterone levels (r = -0.18, P = 0.02 and r = -0.24, P = 0.002, respectively). Alcohol intake was significantly positively correlated with the maternal estradiol level in the 29th week of pregnancy (r = 0.19, P = 0.01), but was unrelated to birth weight. Estrogen level during pregnancy may be regulated by dietary polyunsaturated fatty acids and mediate their effects on fetal growth.

Intrauterine exposures, pregnancy estrogens and breast cancer risk: where do we currently stand?

Since 1990, when a hypothesis on intrauterine influences on breast cancer risk was published, several studies have provided supportive, indirect evidence by documenting associations of birth weight and other correlates of the prenatal environment with breast cancer risk in offspring. Recent results from a unique cohort of women with documented exposure to diethylstilbestrol in utero have provided direct evidence in support of a potential role of pregnancy oestrogens on breast cancer risk in offspring.

Paternal occupational exposure to electro‐magnetic fields as a risk factor for cancer in children and young adults: A case‐control study from the North of England

Numerous studies have implied that paternal occupational exposures, in particular electromagnetic fields (EMF) and ionizing radiation, may be involved in the etiology of childhood cancers. We investigated whether an association exists between paternal occupations at birth involving such exposures and cancer risk in offspring, using data from the Northern Region Young Persons' Malignant Disease Registry (NRYPMDR). Cases (n=4,723) were matched, on sex and year of birth, to controls from two independent sources: (i) all other patients from the NRYPMDR with a different cancer, (ii) 100 cancer-free individuals per case from the Cumbrian Births Database. An occupational exposure matrix was used to assign individuals to exposure groups. There was an increased risk of leukemia among the offspring of men employed in occupations likely to be associated with EMF or radiation exposures (OR 1.31, 95% CI 1.02-1.69), particularly in males aged less than 6 years (OR 1.81, 95% 1.19-2.75). No significant association was seen in females. Increased risks were also seen for chondrosarcoma (OR 8.7, 95% CI 1.55-49.4) and renal carcinoma (OR 6.75, 95% CI 1.73-26.0). These associations were consistent between control groups and remained after adjustment for socio-economic status. This large case-control study identified a significantly increased risk of leukemia among the offspring of men likely to have been occupationally exposed to EMF, with differing associations between males and females. Increased risks of chondrosarcoma and renal carcinoma were also seen, although based on smaller numbers. Further detailed investigations in this area are required to understand this association.

Association of paternal age at birth and the risk of breast cancer in offspring: a case control study

BackgroundOlder paternal age may increase the germ cell mutation rate in the offspring. Maternal age may also mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea.MethodsHistologically confirmed breast cancer cases (n = 1,011) and controls (n = 1,011) with no present or previous history of cancer, matched on year of birth and menopausal status, were selected from several teaching hospitals and community in Seoul during 1995–2003. Information on paternal and maternal ages and other factors was collected by interviewed questionnaire. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression model adjusting for family history of breast cancer in 1st or 2nd degree relatives, and lifetime estrogen exposure duration.ResultsThe risk of breast cancer significantly increased as the paternal age increased (p for trend = 0.025). The association was stronger after controlling for maternal age; women whose fathers were aged ≥40 years at their birth had 1.6-fold increased risk of breast cancer compared with fathers aged <30 years. This association was profound in breast cancer cases in premenopausal women (OR = 1.9, 95% CI = 1.12–3.26, for paternal aged ≥40 vs. <30) (p for trend = 0.031). Although the risk of breast cancer increased as maternal age increased up to the intermediate, and then reduced; the risks in women whose mother were aged 25–29, 30–34, and ≥35 yrs at birth compared to women whose mothers were aged <25 years, were 1.2, 1.4, and 0.8, respectively, the trend was not significant (p for trend = 0.998).ConclusionThese findings suggest that older paternal age increases the risk of breast cancer in their female offspring.

Towards an integrated model for breast cancer etiology: The crucial role of the number of mammary tissue-specific stem cells

Perinatal events and conditions, notably birth weight, are associated with breast cancer risk in offspring, and correlates of mammary gland mass are predictors of breast cancer risk. These findings may be interpreted as indicating that high levels of estrogens and components of the insulin-like growth factor system during pregnancy favour the generation of mammary tissue-specific stem cells, and that the number of these cells, which is positively associated with mammary gland mass, is an important determinant of breast cancer risk. Perinatal events and conditions may also affect risk for other malignancies, but the evidence in the case of breast cancer is prominent, possibly because estrogens and the insulin-like growth factor system are both involved in breast cancer etiology and affect birth weight.

Cancer risk in offspring of male pesticide applicators in agriculture in Sweden

Aims: To explore cancer risk from date of birth until 1994 in children, born 1958 or later, of Swedish male pesticide applicators. Methods: Records of male pesticide applicators licensed 1965–76...

Associations of maternal and umbilical cord hormone concentrations with maternal, gestational and neonatal factors (United States).

Risks of some cancers in adults have been associated with several pregnancy factors, including greater maternal age and birth weight. For hormone-related cancers, these effects are hypothesized to be mediated through higher in utero estrogen concentrations. In addition, racial differences in pregnancy hormone levels have been suggested as being responsible for differences in testicular and prostate cancer risk by race. However, data on hormonal levels related to these characteristics of pregnancy are sparse, particularly those from studies of the fetal circulation. Estrogen and androgen concentrations were measured in maternal and umbilical cord sera from 86 normal, singleton pregnancies. Birth size measures (weight, length and head circumference) were positively correlated with maternal estriol (r = 0.25-0.36) and with cord DHEAS concentrations (r = 0.24-0.41), but not with estrogens in cord sera. Maternal age was inversely correlated with maternal DHEAS, androstenedione and testosterone concentrations (r = -0.30, -0.25 and -0.30, respectively), but uncorrelated with estrogens in either the maternal or cord circulation. Black mothers had higher androstenedione and testosterone concentrations than white mothers, however, there were no racial differences in any of the androgens in cord sera. Cord testosterone concentrations were higher in mothers of male fetuses, while both maternal and cord concentrations of estriol were lower in these pregnancies. These data demonstrate associations between hormone concentrations and pregnancy factors associated with offspring's cancer risk, however, the hormones involved and their patterns of association differ by whether the maternal or fetal circulation was sampled. Hormone concentrations in the fetal circulation in this study are not consistent with the hypothesis that greater estrogen concentrations in high birth weight babies mediate the positive association with breast cancer risk observed in epidemiologic studies, or with the hypothesis that higher testosterone exposure in the in utero environment of black males explains their higher subsequent prostate cancer risk.

FAMILIAL BLADDER CANCER IN THE NATIONAL SWEDISH FAMILY CANCER DATABASE

We analyzed the risk of bladder cancer in offspring according to parental and sibling cancer using the national Swedish Family Cancer Database. Cancer data were obtained from the Swedish Cancer Registry for 1958 to 1996, including 2,105 cases of bladder cancer in offspring. The standardized incidence ratio was used to measure cancer risk in offspring according to familial cancer status. The incidence ratio of bladder cancer increased in Sweden from 1958 to 1996 and it was 3 to 4-fold higher in males than in females. We identified 65 families in which the parents and offspring had bladder cancer with a familial risk of 1.35 (95% confidence interval [CI] 0.97 to 1.79) in sons and 2.29 (95% CI 1.46 to 3.29) in daughters. Discordant cancer sites associated with bladder cancer in the 2 generations were the kidney and thyroid with a standardized incidence ratio of 1.58 (95% CI 1.18 to 2.05) and 1.89 (95% CI 1.00 to 3.05), respectively. Sibling risk was higher compared with offspring risk with a standardized incidence ratio of 2.96 (95% CI 1.41 to 5.08) and in males there was a statistically significant ratio of sibling-to-offspring risk of 2.66 (95% CI 1.29 to 5.45). Patient age at onset modified the familial risk. The highest familial risk of 7.26 (95% CI 2.61 to 14.24) was observed in the brothers of bladder cancer probands diagnosed before age 45 years. The relatively high ratio of sibling-to-offspring risk as well as observed gender specific effects in bladder cancer may reflect an X linked susceptibility gene.

Childhood cancer and parental occupation in the Swedish Family-Cancer Database.

We used the nationwide Swedish Family-Cancer Database to analyze the risk for common childhood tumors in offspring in relation to parental occupation recorded in the census of 1960. A total of 8158 cancer cases, diagnosed before age 15 between years 1958 and 1996, were included. Standardized incidence ratios were calculated using 52 different parental occupations. Among the maternal occupations, seven were associated with the risk of cancer in offspring. Assistant nurses had an excess of children with leukemia and connective tissue and colon cancers. Children of female cooks had brain cancers at a rate greater than expected. Fifteen different malignancies were associated with children of male workers. Shoe and leathers workers' children had excesses of many tumors. Among the other paternal occupations associated with childhood tumors, miners, quarrymen, and hairdressers were likely to be exposed to harmful dusts and chemicals.

Risk of cancer in offspring of women who underwent in vitro fertilization

Risk of cancer in offspring of women who underwent in vitro fertilization

Risk of cancer in offspring of women who underwent in vitro fertilization

Risk of cancer in offspring of women who underwent <i>in vitro</i> fertilization

Increased cancer risk in offspring of women with colorectal carcinoma

Colorectal carcinoma is one of the most common malignancies in the Western population, and a considerable proportion of colorectal carcinomas are estimated to have a familial background. Individuals whose mothers were diagnosed with colon carcinoma or rectal carcinoma from 1958 to 1993, a total of 1. 48 million person-years, constituted the cohort of this Swedish population-based register study. The children were born during the period 1941-1993, and the cancer incidence was observed during the period 1961-1993, with the expected national Swedish incidence used as a reference. A significantly increased risk of colon carcinoma, rectal carcinoma, and non-Hodgkin lymphoma was observed in the cohort. The cancer risk was more pronounced in children whose mothers were age < 50 years at the time of diagnosis or had developed metachronous colorectal carcinoma. Whereas colon carcinoma in the proband implied an increased risk for both colon tumors and rectal tumors, the offspring of women who were diagnosed with rectal carcinoma were at increased risk of developing rectal carcinoma, but no significantly altered risk of colon carcinoma was observed. In the cohort, the cumulative risk for colorectal carcinoma before age 50 years was increased about 3.0 times compared with the general population. This report shows a significant familial aggregation of colorectal carcinoma, demonstrates possible differences in hereditary pattern between colon carcinoma and rectal carcinoma, and confirms that younger age at the time of diagnosis or the occurrence of metachronous tumors indicate familial carcinoma.

Increased cancer risk in offspring of women with colorectal carcinoma

Increased cancer risk in offspring of women with colorectal carcinoma