Susan E. Carozza

Parental age and risk of childhood cancer: a pooled analysis.

Background: Few risk factors for childhood cancer are well-established. We investigated whether advancing parental age increases childhood cancer risk. Methods: We assessed the relationship between parental age and childhood cancer in a case-control study using pooled population-based data. Our pooling was based on linked cancer and birth registry records from New York, Washington, Minnesota, Texas, and California. Subjects included 17,672 cancer cases diagnosed at ages 0–14 years during 1980–2004 and 57,966 controls born during 1970–2004. Individuals with Down syndrome were excluded. Odds ratios and 95% confidence intervals were calculated by logistic regression for the association between parental age and childhood cancer after adjustment for sex, birth weight, gestational age, birth order, plurality, maternal race, birth year, and state. Results: Positive linear trends per 5-year maternal age increase were observed for childhood cancers overall (odds ratio = 1.08 [95% confidence interval = 1.06–1.10]) and 7 of the 10 most frequent diagnostic groups: leukemia (1.08 [1.05–1.11]), lymphoma (1.06 [1.01–1.12]), central nervous system tumors (1.07 [1.03–1.10]), neuroblastoma (1.09 [1.04–1.15]), Wilms’ tumor (1.16 [1.09–1.22]), bone tumors (1.10 [1.00–1.20]), and soft tissue sarcomas (1.10 [1.04–1.17]). No maternal age effect was noted for retinoblastoma, germ cell tumors, or hepatoblastoma. Paternal age was not independently associated with most childhood cancers after adjustment for maternal age. Conclusions: Our results suggest that older maternal age increases risk for most common childhood cancers. Investigation into possible mechanisms for this association is warranted.

Cancer risk among children with very low birth weights.

OBJECTIVE: The risk of hepatoblastoma is strongly increased among children with very low birth weight (<1500 g). Because data on very low birth weight and other childhood cancers are sparse, we examined the risk of malignancy with very low birth weight in a large data set. METHODS: We combined case-control data sets created by linking the cancer and birth registries of California, Minnesota, New York, Texas, and Washington states, which included 17672 children diagnosed as having cancer at 0 to 14 years of age and 57966 randomly selected control subjects. Unconditional logistic regression analysis was used to examine the association of cancer with very low birth weight and moderately low birth weight (1500–1999 g and 2000–2499 g, respectively), compared with moderate/high birth weight (≥2500 g), with adjustment for gender, gestational age, birth order, plurality, maternal age, maternal race, state, and year of birth. RESULTS: Most childhood cancers were not associated with low birth weights. However, retinoblastomas and gliomas other than astrocytomas and ependymomas were possibly associated with very low birth weight. The risk of other gliomas was also increased among children weighing 1500 to 1999 g at birth. CONCLUSIONS: These data suggested no association between most cancers and very low birth weight, with the exception of the known association of hepatoblastoma and possibly moderately increased risks of other gliomas and retinoblastoma, which may warrant confirmation.

Cancer incidence in adolescents and young adults in the United States, 1992–1997

PURPOSE To examine cancer incidence patterns among adolescents and young adults in the United States. METHODS Cancer incidence data from 26 population-based central cancer registries for 1992-1997 were used. Individual cancers were grouped into specific diagnostic groups and subgroups using an integrated classification scheme. The integrated scheme was developed for this study and was based on the most commonly used schemes in population-based epidemiologic studies: Surveillance, Epidemiology, and End Results Programs site groups, International Classification of Childhood Cancer, and International Agency for Research on Cancers Histological Groups for Comparative Studies. Percent distributions and age-specific incidence rates per million population were computed for adolescents (aged 15-19 years) and young adults (aged 20-24 years) by gender. RESULTS The data for 26,010 cancer cases were examined. Among 15-19-year-olds, the five most common cancers were Hodgkins disease, leukemia, cancer in the brain and other nervous system, bone cancer, and non-Hodgkins disease. Among 20-24-year-olds, the five most common cancers were Hodgkins disease, testicular cancer, thyroid cancer, melanoma of the skin, and leukemia. The proportions and rates of the histologic subtypes for most of the common cancers changed with advancing age. For example, among 15-19-year-olds, acute lymphocytic leukemia accounted for approximately 60% of leukemias in males and 50% in females. Among 20-24-year-olds, however, the corresponding percentages of acute lymphocytic leukemia were 37% in males and 31% in females. For ovarian cancer, the germ cell tumor was the most common subtype (54.6% of all ovarian cancers) among 15-19-year-olds. In contrast, ovarian carcinoma was the predominant subtype (70.4%) among 20-24-year-olds. For both age groups, the incidence rates of nodular Hodgkins disease, melanoma of the skin, and thyroid cancer were significantly greater in females than in males. CONCLUSIONS Cancer incidence patterns among adolescents and young adults are distinctive. In these age groups, a transition from predominantly pediatric histologic subtypes to adult subtypes was observed for Hodgkins disease, leukemia, ovarian cancer, and soft tissue sarcoma. Gender differences were found for Hodgkins disease, melanoma of the skin, and thyroid cancer.

Birth weight, ethnicity, and occurrence of cancer in children: a population-based, incident case-control study in the State of Texas, USA

Objective: To investigate the relationship between birth weight and risk of early age childhood cancer and whether racial differences in birth weight distribution could explain differences in the incidence of cancer in white, Hispanic, and black children. Methods: We compared birth weights of 268 children younger than five years old and diagnosed with cancer in the State of Texas in 1995 to the birth weights of 2680 randomly selected, age-matched population-based controls. Birth weight, sex, race/ethnicity, maternal age, smoking status, parity, and gestational age information was ascertained from the birth certificates. Logistic regression analyses were performed to evaluate the association between high birth weight (> 4000 g) and occurrence of childhood cancer. Results: Increased odds ratios (OR) were found for “total cancer cases” (OR 1.4, 95% CI 0.9–2.1), “leukemia cases” (OR 1.7, 95% CI 0.9–3.0) and “acute lymphoblastic leukemia (ALL) cases” (OR 2.2, 95% CI 1.2–4.1). Increased ORs in the former two groups were shown to be due to ALL cases. Including the race/ethnicity variable in the regression model did not affect the ORs. Conclusion: Compared to newborns who weighed between 2500 and 4000 g at birth, children who weighed > 4000 g had an increased risk of developing childhood ALL during the first five years of life. Birth weight differences does not explain the sequence of childhood cancer incidence by race/ethnicity.

DNA Repair Polymorphisms XRCC1 and MGMT and Risk of Adult Gliomas

X-ray cross complementing group 1 (XRCC1) and O6-methylguanine-DNA methyltransferase (MGMT) are pivotal repair genes focused on repairing lesions due to ionizing radiation, alkylating agents, and oxidative DNA damage, risk factors previously linked to gliomas. Using the population based San Francisco Adult Glioma study, we evaluated associations between XRCC1 Arg399Gln, MGMT Leu84Phe, and MGMT Ile143Val polymorphisms with glioma risk among white cases (n = 441 to 453) and controls (n = 487 to 526). We found no evidence of an association between XRCC1 genotypes and glioma. We observed a weak positive association for the MGMT Leu84Phe polymorphism (Leu or Phe/Phe versus Leu/Leu: adjusted OR = 1.26; CI 0.90–1.75) and the MGMT Ile143Val polymorphism (Ile or Val/Val versus Ile/Ile: adjusted OR = 1.20; CI 0.85–1.71).

Birth order and risk of childhood cancer: A pooled analysis from five US States

The causes of childhood cancers are largely unknown. Birth order has been used as a proxy for prenatal and postnatal exposures, such as frequency of infections and in utero hormone exposures. We investigated the association between birth order and childhood cancers in a pooled case‐control dataset. The subjects were drawn from population‐based registries of cancers and births in California, Minnesota, New York, Texas and Washington. We included 17,672 cases <15 years of age who were diagnosed from 1980 to 2004 and 57,966 randomly selected controls born 1970–2004, excluding children with Down syndrome. We calculated odds ratios and 95% confidence intervals using logistic regression, adjusted for sex, birth year, maternal race, maternal age, multiple birth, gestational age and birth weight. Overall, we found an inverse relationship between childhood cancer risk and birth order. For children in the fourth or higher birth order category compared to first‐born children, the adjusted OR was 0.87 (95% CI: 0.81, 0.93) for all cancers combined. When we examined risks by cancer type, a decreasing risk with increasing birth order was seen in the central nervous system tumors, neuroblastoma, bilateral retinoblastoma, Wilms tumor and rhabdomyosarcoma. We observed increased risks with increasing birth order for acute myeloid leukemia but a slight decrease in risk for acute lymphoid leukemia. These risk estimates were based on a very large sample size, which allowed us to examine rare cancer types with greater statistical power than in most previous studies, however the biologic mechanisms remain to be elucidated.

Agricultural pesticides and risk of childhood cancers

Agricultural pesticide applications have the potential for significant drift beyond the target spray area and may result in exposure to non-farming residents in surrounding communities. Using geographic information system (GIS) methods, 1778 childhood cancer cases and 1802 controls born in Texas between 1990 and 1998 were assigned probable agricultural pesticide exposure based on proximity of birth residence to crop fields. Multivariate modeling was used to estimate odds ratios and 95% confidence intervals for selected cancers. For most childhood cancers, we found no evidence of elevated risk associated with residential proximity at birth to cropland. There was an overall pattern of increased risk for germ-cell tumors but the odds ratios were based on few number of exposed cases. There was also some indication of increased risk for non-Hodgkin lymphoma (NHL) and Burkitt lymphoma, but point estimates were imprecise and not statistically significant. Previous studies have assessed pesticide exposure primarily based on parental occupational history or household use, while our focus was on agricultural pesticides and so may represent a different array of chemical agents occurring at lower doses.

Occupation and adult gliomas in the San Francisco Bay Area

The etiology of gliomas is not well understood. Some jobs might involve sustained and elevated exposures to carcinogens. This study compares lifetime job histories of 879 glioma cases diagnosed between August 1991 to April 1994 and May 1997 to August 1999 in the San Francisco Bay Area and 864 controls. Logistic analyses compared longest and ever held occupations of 1 year or more for all astrocytic and nonastrocytic cases and controls overall with adjustment for age, gender, and ethnicity and separately for men and women. Two-fold or higher or statistically significant elevated odds ratios were found overall and in men among those with longest held occupations, as firefighters, physicians, material moving equipment operators, and janitors; such elevated odds ratios were also observed for longest-held occupations among male motor vehicle operators and personal service workers and female messengers, legal/social service workers, electronic equipment operators, painters, and food processors. Odds ratios of 0.50 or less, but not statistically significant, were found for those with longest held jobs as writers/journalists, biological scientists, paper workers, mechanics, chemists, and photographers/photoprocessors. This study supports previously observed occupational associations and is one of the few studies with sufficient numbers to separately analyze occupations by gender.

Infant birthweight and risk of childhood cancer: international population-based case control studies of 40 000 cases

BACKGROUND High birthweight is an established risk factor for childhood leukaemia. Its association with other childhood cancers is less clear, with studies hampered by low case numbers. METHODS We used two large independent datasets to explore risk associations between birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls were obtained by linkage of birth to cancer registration records across five US states, and 23 772 cases and 33 206 controls were obtained from the UK National Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age, birth order, plurality, and maternal age and race/ethnicity. RESULTS Risk associations were found between birthweight and several childhood cancers, with strikingly similar results between datasets. Total cancer risk increased linearly with each 0.5 kg increase in birthweight in both the US [odds ratio 1.06 (95% confidence interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK: 1.12 (1.06, 1.19)] and soft tissue sarcomas [USA: 1.12 (1.05, 1.20), UK: 1.07 (1.00, 1.13)]. In contrast, increasing birthweight decreased the risk of hepatic tumours [USA: 0.77 (0.69, 0.85), UK: 0.79 (0.71, 0.89) per 0.5 kg increase]. Associations were also observed between high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant melanomas. For some cancer subtypes, risk associations with birthweight were non-linear. We observed no association between birthweight and risk of retinoblastoma or bone tumours. CONCLUSIONS Approximately half of all childhood cancers exhibit associations with birthweight. The apparent independence from other factors indicates the importance of intrauterine growth regulation in the aetiology of these diseases.

Birth characteristics and the risk of childhood rhabdomyosarcoma based on histological subtype.

Background:Little is known about risk factors for childhood rhabdomyosarcoma (RMS) and the histology-specific details are rare.Methods:Case–control studies formed by linking cancer and birth registries of California, Minnesota, New York, Texas and Washington, which included 583 RMS cases (363 embryonal and 85 alveolar RMS) and 57 966 randomly selected control subjects, were analysed using logistic regression. The associations of RMS (overall, and based on embryonal or alveolar histology) with birth weight across five 500 g categories (from 2000 to 4500 g) were examined using normal birth weight (2500–3999 g) as a reference. Large (>90th percentile) and small (<10th percentile) size for gestational age were calculated based on birth weight distributions in controls and were similarly examined.Results:High birth weight increased the risk of embryonal RMS and RMS overall. Each 500 g increase in birth weight increased the risk of embryonal RMS (odds ratio (OR)=1.27, 95% confidence interval (CI)=1.14–1.42) and RMS overall (OR=1.18, 95% CI=1.09–1.29). Large size for gestational age also significantly increased the risk of embryonal RMS (OR=1.42, 95% CI=1.03–1.96).Conclusions:These data suggest a positive association between accelerated in utero growth and embryonal RMS, but not alveolar RMS. These results warrant cautious interpretation owing to the small number of alveolar RMS cases.