Prospective analysis of sleep characteristics, chronotype, and risk of breast cancer in the california teachers study.

PURPOSE: Poor sleep quality and evening chronotype were associated with increased risk of breast cancer in a previous retrospective study in the California Teachers Study (CTS). The present analysis examines these sleep factors prospectively in the same cohort of women. METHODS: From the CTS, we included 1,085 incident breast cancer cases and 38,470 cancer-free participants from 2012 through 2019. We calculated time at risk and used Cox proportional hazards regression models to estimate the hazard ratios (HRs) and control for risk factors such as age, race, body mass index, family history of breast cancer, and reproductive history. The sleep factors examined were quality, latency, duration, disturbance, and sleep medication use, based on a shortened version of the Pittsburgh Sleep Quality Index, as well as chronotype (preference for morning or evening activity). This analysis was limited to women who were post-menopausal at the time they answered these sleep-related questions. RESULTS: Measures of sleep quality did not appear to be associated with subsequent breast cancer risk. The HR for evening chronotypes compared to morning chronotypes was somewhat elevated (HR 1.19, 95% CI 1.04, 1.36). CONCLUSION: While the measures of sleep quality and duration were not associated with post-menopausal breast cancer risk in this prospective analysis, the modestly elevated risk observed for evening chronotypes was consistent with the prior retrospective analysis.

Neighborhood attributes and cardiovascular disease risk in breast cancer survivors: The Pathways Study.

BACKGROUND: Breast cancer survivors are at a higher risk of cardiovascular disease (CVD) morbidity and mortality compared with the general population. The impact of objective social and built neighborhood attributes on CVD risk in a cohort of female breast cancer survivors was examined. METHODS: The 3975 participants came from the Pathways Study, a prospective cohort of women with invasive breast cancer from an integrated health care system in northern California. Women diagnosed with breast cancer from 2006 through 2013 were enrolled on average approximately 2 months after diagnosis. Their baseline addresses were geocoded and appended to neighborhood attributes for racial/ethnic composition, socioeconomic status (SES), population density, urbanization, crime, traffic density, street connectivity, parks, recreational facilities, and retail food environment. Incident CVD events included ischemic heart disease, heart failure, cardiomyopathy, or stroke. Cox proportional hazards models estimated associations of neighborhood attributes with CVD risk, which accounted for clustering by block groups. Fully adjusted models included sociodemographic, clinical, and behavioral factors. RESULTS: During follow-up through December 31, 2018, 340 participants (8.6%) had CVD events. A neighborhood racial/ethnic composition measure, percent of Asian American/Pacific Islander residents (lowest quintile hazard ratio [HR], 1.85; 95% CI, 1.03-3.33), and crime index (highest quartile HR, 1.48; 95% CI, 1.08-2.03) were associated with the risk of CVD events independent of individual SES, hormone receptor status, treatment, cardiometabolic comorbidities, body mass index, and physical activity. CONCLUSIONS: With the application of a socio-ecological framework, how residential environments shape health outcomes in women with breast cancer and affect CVD risk in this growing population can be understood.

The influence of neighborhood socioeconomic status and ethnic enclave on endometrial cancer mortality among Hispanics and Asian Americans/Pacific Islanders in California.

PURPOSE: We investigated the role of neighborhood socioeconomic status (nSES) and residence in ethnic enclaves on mortality following endometrial cancer (EC) diagnosis among Hispanics and Asian Americans/Pacific Islanders (AAPI). METHODS: Using California Cancer Registry data, enhanced with census block group information on ethnic enclave and nSES, we examined 9,367 Hispanics and 5,878 AAPIs diagnosed with EC from 1988 to 2011. Cox proportional hazard models were used to estimate associations between all-cause and EC-specific mortality with nSES and ethnic enclaves, adjusting for subject sociodemographic and tumor characteristics. RESULTS: Hispanics in the lowest SES neighborhoods had a 39% and 36% increased risk of all-cause and EC-specific mortality, respectively, compared to Hispanics in the highest SES neighborhoods. AAPIs in the lowest SES neighborhoods had a 37% increased risk of all-cause mortality compared to AAPIs in the highest SES neighborhoods. Living in an ethnic enclave was associated with lower all-cause mortality risk for AAPIs. CONCLUSIONS: Mortality risk varied by nSES and ethnic enclave among Hispanics and AAPIs. Women living in lower SES communities experienced significantly higher risk, highlighting the need to identify the specific neighborhood factors underlying these associations so that community-based interventions may be properly targeted.

Evaluating an owner-to-worker training intervention in California nail salons using personal air monitoring.

BACKGROUND: Chemicals in nail products have been linked to numerous health concerns. METHODS: We recruited Vietnamese-American nail salon owners and workers in California and randomized salons into an intervention or control group. Owners in the intervention group received training and then provided education to workers in their salons on best practices to reduce workplace chemical exposures. Methyl methacrylate (MMA), toluene, and total volatile organic compounds (TVOCs) were measured using personal air monitors worn by workers during the work-shift. RESULTS: We enrolled 77 salons (37 intervention and 40 control) and 200 workers. There was no significant intervention effect between the two groups. However, MMA and TVOCs were higher for workers who used gel polish and acrylic nails as well as in busy salons. CONCLUSIONS: Although the intervention did not show reductions in chemical levels, identifying worker tasks and salon characteristics that predict chemical levels can inform future interventions to reduce exposures.

Tracing a Path to the Past: Exploring the Use of Commercial Credit Reporting Data to Construct Residential Histories for Epidemiologic Studies of Environmental Exposures.

Large-scale environmental epidemiologic studies often rely on exposure estimates based on linkage to residential addresses. This approach, however, is limited by the lack of residential histories typically available for study participants. Our objective was to evaluate the feasibility of using address data from LexisNexis (a division of RELX, Inc., Dayton, Ohio), a commercially available credit reporting company, to construct residential histories for participants in the California Teachers Study (CTS), a prospective cohort study initiated in 1995-1996 to study breast cancer (n = 133,479). We evaluated the degree to which LexisNexis could provide retrospective addresses prior to study enrollment, as well as the concordance with existing prospective CTS addresses ascertained at the time of the completion of 4 self-administered questionnaires. For approximately 80% of CTS participants, LexisNexis provided at least 1 retrospective address, including nearly 25,000 addresses completely encompassed by time periods prior to enrollment. This approach more than doubled the proportion of the study population for whom we had an address of residence during the childbearing years-an important window of susceptibility for breast cancer risk. While overall concordance between the prospective addresses contained in these 2 data sources was good (85%), it was diminished among black women and women under the age of 40 years.

Breast cancer in Asian Americans in California, 1988-2013: increasing incidence trends and recent data on breast cancer subtypes.

PURPOSE: In contrast to other US racial/ethnic groups, Asian Americans (AA) have experienced steadily increasing breast cancer rates in recent decades. To better understand potential contributors to this increase, we examined incidence trends by age and stage among women from seven AA ethnic groups in California from 1988 to 2013, and incidence patterns by subtype and age at diagnosis for the years 2009 through 2013. METHODS: Joinpoint regression was applied to California Cancer Registry data to calculate annual percentage change (APC) for incidence trends. Incidence rate ratios were used to compare rates for AA ethnic groups relative to non-Hispanic whites (NHW). RESULTS: All AA groups except Japanese experienced incidence increases, with the largest among Koreans in 1988-2006 (APC 4.7, 95% CI 3.8, 5.7) and Southeast Asians in 1988-2013 (APC 2.5, 95% CI 0.8, 4.2). Among women younger than age 50, large increases occurred for Vietnamese and other Southeast Asians; among women over age 50, increasing trends occurred in all AA ethnic groups. Rates increased for distant-stage disease among Filipinas (2.2% per year, 95% CI 0.4, 3.9). Compared to NHW, Filipinas and older Vietnamese had higher incidence rates of some HER2+ subtypes. CONCLUSIONS: Breast cancer incidence rates have risen rapidly among California AA, with the greatest increases in Koreans and Southeast Asians. Culturally tailored efforts to increase awareness of and attention to breast cancer risk factors are needed. Given the relatively higher rates of HER2-overexpressing subtypes in some AA ethnicities, research including these groups and their potentially unique exposures may help elucidate disease etiology.

Functional IGF1R variant predicts breast cancer risk in women with preeclampsia in California Teachers Study.

PURPOSE: Hypertension in pregnancy has been associated with decreased future risk of breast cancer in many but not all studies. In the Marin Women's Study, pregnancy-induced hypertension was shown to interact with the T allele of a functional IGF1R gene variant, rs2016347, to result in lower breast density, as well as decreased breast cancer risk. Our objective was to explore these findings in a larger sample of women from the California Teachers Study (CTS). METHODS: The CTS cohort consists of over 130,000 female educators. DNA was available from a nested case-control study, which included 2,030 non-Hispanic white women who developed breast cancer and 1,552 controls. The current study included all participants from the case-control group with a self-reported history of preeclampsia (80 cases/57 controls). RESULTS: Comparing TT to GG genotypes revealed adjusted odds ratios of 0.38 (CI 0.13, 1.14) for all invasive breast cancers, 0.26 (CI 0.07, 0.89) for hormone receptor-positive (HR+) breast cancers, 0.15 (CI 0.04, 0.56) for those with age at first birth (AFB) < 30, and 0.10 (CI 0.02, 0.49) for those with AFB < 30 and HR+ breast cancers. Trend analysis yielded p values of 0.09, 0.03, 0.005, and 0.004 respectively, suggesting a biological effect for each T allele. CONCLUSION: Study findings indicate that the T allele of IGF1R variant rs2016347 is associated with a significant reduction in breast cancer risk in women with a history of preeclampsia, most marked for HR+ breast cancer and in women with AFB < 30.

An Investigation of Connections between Birth Defects and Cancers Arising in Adolescence and Very Young Adulthood.

This study investigated the relationship between birth defects and cancer in adolescents and very young adults using California's population-based registries. Although overall cancer risk was elevated among individuals with chromosomal birth defects, this was not observed in those with nonchromosomal birth defects, as was demonstrated previously in younger children.

Parental Age and Risk of Infant Leukaemia: A Pooled Analysis.

BACKGROUND: Infant leukaemia (IL) is extremely rare with fewer than 150 cases occurring each year in the United States. Little is known about its causes. However, recent evidence supports a role of de novo mutations in IL aetiology. Parental age has been associated with several adverse outcomes in offspring, including childhood cancers. Given the role of older parental age in de novo mutations in offspring, we carried out an analysis of parental age and IL. METHODS: We evaluated the relationship between parental age and IL in a case-control study using registry data from New York, Minnesota, California, Texas, and Washington. Records from 402 cases [219 acute lymphoblastic leukaemia (ALL), 131 acute myeloid leukaemia (AML), and 52 other] and 45 392 controls born during 1981-2004 were analysed. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Estimates were adjusted for infant sex, birth year category, maternal race, state, and mutually adjusted for paternal or maternal age, respectively. RESULTS: Infants with mothers' age ≥40 years had an increased risk of developing AML (OR 4.80, 95% CI 1.80, 12.76). In contrast, paternal age <20 was associated with increased risk of ALL (OR 3.69, 95% CI 1.62, 8.41). CONCLUSION: This study demonstrates increased risk of infant ALL in relation to young paternal age. Given record linkage, there is little concern with recall or selection bias, although data are lacking on MLL gene status and other potentially important variables. Parent of origin effects, de novo mutations, and/or carcinogenic exposures may be involved in IL aetiology.

Representativeness of breast cancer cases in an integrated health care delivery system.

BACKGROUND: Integrated health care delivery systems, with their comprehensive and integrated electronic medical records (EMR), are well-poised to conduct research that leverages the detailed clinical data within the EMRs. However, information regarding the representativeness of these clinical populations is limited, and thus the generalizability of research findings is uncertain. METHODS: Using data from the population-based California Cancer Registry, we compared age-adjusted distributions of patient and neighborhood characteristics for three groups of breast cancer patients: 1) those diagnosed within Kaiser Permanente Northern California (KPNC), 2) non-KPNC patients from NCI-designated cancer centers, and 3) those from all other hospitals. RESULTS: KPNC patients represented 32 % (N = 36,109); cancer center patients represented 7 % (N = 7805); and all other hospitals represented 61 % (N = 68,330) of the total breast cancer patients from this geographic area during 1996-2009. Compared with cases from all other hospitals, KPNC had slightly fewer non-Hispanic Whites (70.6 % versus 74.4 %) but more Blacks (8.1 % versus 5.0 %), slightly more patients in the 50-69 age range and fewer in the younger and older age groups, a slightly lower proportion of in situ but higher proportion of stage I disease (41.6 % versus 38.9 %), were slightly less likely to reside in the lowest (4.2 % versus 6.5 %) and highest (36.2 % versus 39.0 %) socioeconomic status neighborhoods, and more likely to live in suburban metropolitan areas and neighborhoods with more racial/ethnic minorities. Cancer center patients differed substantially from patients from KPNC and all other hospitals on all characteristics assessed. All differences were statistically significant (p < .001). CONCLUSIONS: Although much of clinical research discoveries are based in academic medical centers, patients from large, integrated medical centers are likely more representative of the underlying population, providing support for the generalizability of cancer research based on electronic data from these centers.

Adverse birth outcomes and maternal complications in licensed cosmetologists and manicurists in California.

PURPOSE: Due to concerns around occupational chemical exposures, this study sought to examine whether women working as cosmetologists (providing hair and nail care services) and manicurists (providing only nail care services) have an elevated risk for adverse pregnancy outcomes. METHODS: In this population-based retrospective study of cosmetologists and manicurists in California, we linked cosmetology licensee and birth registry files to identify births during 1996-2009. We compared outcomes among cosmetologists and manicurists to those of the general female population and to women from other industries. We also conducted restricted analyses for Vietnamese women, who comprise a significant proportion of the workforce. RESULTS: There was little evidence of increased risk for adverse birth outcomes, but we observed an association for small for gestational age (SGA) among Vietnamese manicurists (OR 1.39; 95 % CI 1.08-1.78) and cosmetologists (OR 1.40; 95 % CI 1.08-1.83) when compared to other working women. Some maternal complications were observed, notably an increased risk for gestational diabetes (OR 1.28; 95 % CI 1.10-1.50 for manicurists; OR 1.19; 95 % CI 1.07-1.33 for cosmetologists) compared with the general population, which further elevated when restricted to Vietnamese workers (OR 1.59; 95 % CI 1.20-2.11 for manicurists; OR 1.49; 95 % CI 1.04-2.11 for cosmetologists). Additionally, we observed an association for placentia previa among manicurists (OR 1.46; 95 % CI 1.08-1.97) and cosmetologists (OR 1.22; 95 % CI 1.02-1.46) compared with the general population. CONCLUSIONS: Women in the nail and hair care industry may be potentially at increased risk for some maternal complications, although further research is warranted. Vietnamese workers may also have increased risk for SGA.

Representativeness of Patients With Lung Cancer in an Integrated Health Care Delivery System.

INTRODUCTION: Observational research is important for understanding the real-world benefits of advancements in lung cancer care. Integrated health care systems, such as Kaiser Permanente Northern California, have extensive electronic health records suitable for such research, but the generalizability of their populations is often questioned. METHODS: Leveraging data from the California Cancer Registry, the authors compared distributions of demographic and clinical characteristics, in addition to neighborhood and environmental conditions, between patients diagnosed with lung cancer from 2015 through 2019 at Kaiser Permanente Northern California, National Cancer Institute-designated cancer centers (NCICCs), and all other non-NCICC hospitals within the same catchment area. RESULTS: Of 20,178 included patients, 30% were from Kaiser Permanente Northern California, 8% from NCICCs, and 62% from other non-NCICC hospitals. Compared to NCICC patients, Kaiser Permanente Northern California patients were more similar to other non-NCICC patients on most characteristics. Compared to other non-NCICC patients, Kaiser Permanente Northern California patients were slightly older, more likely to be female, and less likely to be Hispanic or Asian/Pacific Islander and to reside in lower socioeconomic status (SES) neighborhoods. In contrast, NCICC patients were younger, less likely to be female or from non-Asian/Pacific Islander minoritized racial groups, and more likely to present with early-stage disease and adenocarcinoma and to reside in neighborhoods with higher SES and lower air pollution than Kaiser Permanente Northern California or other non-NCICC patients. DISCUSSION: Patients from Kaiser Permanente Northern California, compared to NCICCs, are more broadly representative of the underlying patient population with lung cancer. CONCLUSION: Research using electronic health record data from integrated health care systems can contribute generalizable real-world evidence to benchmark and improve lung cancer care.

Reducing chemical exposures in nail salons through owner and worker trainings: an exploratory intervention study.

BACKGROUND: Nail salons represent a rapidly growing industry with mainly Vietnamese immigrant workers. Workers routinely handle nail products containing hazardous compounds, yet have limited accessible information to minimize workplace exposures. METHODS: We conducted a culturally appropriate pilot intervention on workplace chemical exposure reduction strategies. We trained eight Vietnamese owners, who then trained Vietnamese workers in their salons. We conducted pre-, mid-, and post-intervention assessments with workers, including an in-person survey and personal air monitoring of volatile compounds. RESULTS: Survey results suggested statistically significant increases for chemical knowledge and behavioral changes in glove and mask use, and a reduced prevalence of nose, throat, and skin irritations. Air monitoring results showed a net reduction for methyl methacrylate and total volatile organic compounds, but not for toluene. CONCLUSIONS: Worker education disseminated through salon owners to their workers can improve work-related knowledge, behavior, health symptoms, and exposures for select air contaminants, although more research is warranted.

Probabilistic risk assessment of residential exposure to metal(loid)s in a mining impacted community.

The "Gold Country" region of California is impacted by legacy and active gold mines. Concomitantly, Gold Country has an increased rate of female breast cancer relative to the state average. Using community-based participatory research methods, 40 participants completed surveys and collected a total of 354 water, soil, home-grown foods, and dust samples from their homes, which we compared to state, federal, and international contamination standards for arsenic, cadmium, and lead. All soil samples exceeded U.S. EPA and California EPA soil standards for arsenic. When comparing other media to state, federal and international standards for arsenic, cadmium, and lead, 15 additional exceedances for indoor/outdoor dust, drinking water, and/or vegetable were documented. A probabilistic risk assessment was conducted to determine an adult female's exposure to arsenic, cadmium, and lead and estimated risk. Arsenic exposure, due largely to water (63.5 %) and homegrown food (33.3 %), presents carcinogenic risks in excess of the EPA recommended upper limit for contaminated sites (1 × 10-4) in 12.5 % of scenarios, and exceeds a risk level of 1 × 10-6 in 98.0 % of cases. Cadmium exposure results mainly from homegrown food consumption (83.7 %), and lead exposure results from a broader range of sources. This research indicates that rural areas in Gold Country face environmental exposures different than in urban areas. Exposure to arsenic in the female population of Gold Country may be driven by consumption of home-grown foods and water, and exposure to cadmium is driven by home-grown food intake. Since mining sites are of concern internationally, this risk assessment process and associated findings are significant and can be used to inform and tailor public health interventions. The weight of the evidence suggests that the arsenic exposure identified in this study could contribute to increases in the cancer rate among those living in Gold Country, California.

Cancer in children with nonchromosomal birth defects.

OBJECTIVE: To examine whether the incidence of childhood cancer is elevated in children with birth defects but no chromosomal anomalies. STUDY DESIGN: We examined cancer risk in a population-based cohort of children with and without major birth defects born between 1988 and 2004, by linking data from the California Birth Defects Monitoring Program, the California Cancer Registry, and birth certificates. Cox proportional hazards models generated hazard ratios (HRs) and 95% CIs based on person-years at risk. We compared the risk of childhood cancer in infants born with and without specific types of birth defects, excluding infants with chromosomal anomalies. RESULTS: Of the 4869 children in the birth cohort with cancer, 222 had a major birth defect. Although the expected elevation in cancer risk was observed in children with chromosomal birth defects (HR, 12.44; 95% CI, 10.10-15.32), especially for the leukemias (HR, 28.99; 95% CI, 23.07-36.42), children with nonchromosomal birth defects also had an increased risk of cancer (HR, 1.58; 95% CI, 1.33-1.87), but instead for brain tumors, lymphomas, neuroblastoma, and germ cell tumors. CONCLUSION: Children with nonchromosomal birth defects are at increased risk for solid tumors, but not leukemias. Dysregulation of early human development likely plays an important role in the etiology of childhood cancer.

Returning Individual Tap Water Testing Results to Research Study Participants after a Wildfire Disaster.

After the devastating wildfire that destroyed most of the town of Paradise, California in 2018, volatile organic compounds were found in water distribution pipes. Approximately 11 months after the fire, we collected tap water samples from 136 homes that were still standing and tested for over 100 chemicals. Each participant received a customized report showing the laboratory findings from their sample. Our goal was to communicate individual water results and chemical information rapidly in a way that was understandable, scientifically accurate, and useful to participants. On the basis of this process, we developed a framework to illustrate considerations and priorities that draw from best practices of previous environmental results return research and crisis communication, while also addressing challenges specific to the disaster context. We also conducted a follow-up survey on participants' perceptions of the results return process. In general, participants found the results return communications to be understandable, and they felt less worried about their drinking water quality after receiving the information. Over one-third of the participants reported taking some kind of action around their water usage habits after receiving their results. Communication with participants is a critical element of environmental disaster research, and it is important to have a strategy to communicate results that achieves the goals of timeliness, clarity, and scientific accuracy, ultimately empowering people toward actions that can reduce exposure.

Differential newborn DNA methylation among individuals with complex congenital heart defects and childhood lymphoma.

BACKGROUND: There is emerging evidence that children with complex congenital heart defects (CHDs) are at increased risk for childhood lymphoma, but the mechanisms underlying this association are unclear. Thus, we sought to evaluate the role of DNA methylation patterns on "CHD-lymphoma" associations. METHODS: From >3 million live births (1988-2004) in California registry linkages, we obtained newborn dried bloodspots from eight children with CHD-lymphoma through the California BioBank. We performed case-control epigenome-wide association analyses (EWAS) using two comparison groups with reciprocal discovery and validation to identify differential methylation associated with CHD-lymphoma. RESULTS: After correction for multiple testing at the discovery and validation stages, individuals with CHD-lymphoma had differential newborn methylation at six sites relative to two comparison groups. Our top finding was significant in both EWAS and indicates PPFIA1 cg25574765 was hypomethylated among individuals with CHD-lymphoma (mean beta = 0.04) relative to both unaffected individuals (mean beta = 0.93, p = 1.5 × 10-12 ) and individuals with complex CHD (mean beta = 0.95, p = 3.8 × 10-8 ). PPFIA1 encodes a ubiquitously expressed liprin protein in one of the most commonly amplified regions in many cancers (11q13). Further, cg25574765 is a proposed marker of pre-eclampsia, a maternal CHD risk factor that has not been fully evaluated for lymphoma risk in offspring, and the tumor microenvironment that may drive immune cell malignancies. CONCLUSIONS: We identified associations between molecular changes present in the genome at birth and risk of childhood lymphoma among those with CHD. Our findings also highlight novel perinatal exposures that may underlie methylation changes in CHD predisposing to lymphoma.

Association between long-term exposure to particulate air pollution with SARS-CoV-2 infections and COVID-19 deaths in California, U.S.A.

Previous studies have reported associations between air pollution and COVID-19 morbidity and mortality, but most have limited their exposure assessment to a large area, have not used individual-level variables, nor studied infections. We examined 3.1 million SARS-CoV-2 infections and 49,691 COVID-19 deaths that occurred in California from February 2020 to February 2021 to evaluate risks associated with long-term neighborhood concentrations of particulate matter less than 2.5 µm in diameter (PM2.5). We obtained individual address data on SARS-CoV-2 infections and COVID-19 deaths and assigned 2000-2018 1km-1km gridded PM2.5 surfaces to census block groups. We included individual covariate data on age and sex, and census block data on race/ethnicity, air basin, Area Deprivation Index, and relevant comorbidities. Our analyses were based on generalized linear mixed models utilizing a Poisson distribution. Those living in the highest quintile of long-term PM2.5 exposure had risks of SARS-CoV-2 infections 20% higher and risks of COVID-19 mortality 51% higher, compared to those living in the lowest quintile of long-term PM2.5 exposure. Those living in the areas of highest long-term PM2.5 exposure were more likely to be Hispanic and more vulnerable, based on the Area Deprivation Index. The increased risks for SARS-CoV-2 Infections and COVID-19 mortality associated with highest long-term PM2.5 concentrations at the neighborhood-level in California were consistent with a growing body of literature from studies worldwide, and further highlight the importance of reducing levels of air pollution to protect public health.

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.

Birth size and breast cancer risk among young California-born women.

OBJECTIVE: Evaluate the risk of breast cancer associated with birth size among young California-born women. METHODS: Invasive breast cancer cases diagnosed 1988-2004 among women born in California during the 1960s were identified from the California Cancer Registry. Breast cancer cases (n = 3,712) were linked to their California birth records. Controls (n = 8,615) were randomly selected from California birth records for women, frequency matched to cases by birth year. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated from unconditional logistic regression. RESULTS: The adjusted OR for breast cancer associated with the highest category of birth weight (≥4,000 g) was 1.12 (95% CI 0.89-1.41), p-trend = 0.02. The adjusted OR for the highest category of birth length (>20 inches) was 1.13 (95% CI 1.02-1.25), p-trend = 0.02. These relationships appeared to be confined to cases with estrogen receptor positive (ER+) tumors (p-trend ≤0.01) or progesterone receptor positive (PR+) tumors (p-trend ≤0.02). No significant associations were found among cases with ER or PR negative tumors. CONCLUSIONS: Our results confirm previous findings of elevated breast cancer risk associated with increases in birth size. These risks may be confined to ER+ and PR+ tumors, highlighting the potential mechanistic role of sex steroid hormonal pathways.