The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium.

BACKGROUND: Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs. METHODS: In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption. RESULTS: Inverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer. CONCLUSION: Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.

Vitamin E intake from natural sources and head and neck cancer risk: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

BACKGROUND: Evidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited. METHODS: We used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of non-alcohol energy-adjusted vitamin E intake. RESULTS: Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54-0.83, P for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral/pharyngeal cancer. Inverse associations were generally observed for the anatomical subsites of oral and pharyngeal cancer and within covariate strata for both sites. CONCLUSION: Our findings suggest that greater vitamin E intake from foods may lower HNC risk, although we were not able to explain the heterogeneity observed across studies or rule out certain sources of bias.

Prevalence of human papillomavirus among oesophageal squamous cell carcinoma cases: systematic review and meta-analysis.

BACKGROUND: Oncogenic human papillomavirus (HPV) has been hypothesised as a risk factor for oesophageal squamous cell carcinoma (OSCC), but aetiological research has been limited by the varying methodology used for establishing HPV prevalence. The aims of this systematic review and meta-analysis were to estimate the prevalence of HPV DNA detected in OSCC tumours and the influence of study characteristics. METHODS: Study-level estimates of overall and type-specific HPV prevalence were meta-analysed to obtain random-effects summary estimates. RESULTS: This analysis included 124 studies with a total of 13 832 OSCC cases. The average HPV prevalence (95% confidence interval) among OSCC cases was 0.277 (0.234, 0.320) by polymerase chain reaction; 0.243 (0.159, 0.326) by in situ hybridisation; 0.304 (0.185, 0.423) by immunohistochemistry; 0.322 (0.154, 0.490) by L1 serology; and 0.176 (0.061, 0.292) by Southern/slot/dot blot. The highest HPV prevalence was found in Africa and Asia, notably among Chinese studies from provinces with high OSCC incidence rates. CONCLUSIONS: Future research should focus on quantifying HPV in OSCC cases using strict quality control measures, as well as determining the association between HPV and OSCC incidence by conducting large, population-based case-control studies. Such studies will provide a richer understanding of the role of HPV in OSCC aetiology.

Non-steroidal anti-inflammatory drug use, hormone receptor status, and breast cancer-specific mortality in the Carolina Breast Cancer Study.

Epidemiologic studies report a protective association between non-steroidal anti-inflammatory drug (NSAID) use and hormone receptor-positive breast cancer risk, a finding consistent with NSAID-mediated suppression of aromatase-driven estrogen biosynthesis. However, the association between NSAID use and breast cancer-specific mortality is uncertain and it is unknown whether this relationship differs by hormone receptor status. This study comprised 935 invasive breast cancer cases, of which 490 were estrogen receptor (ER)-positive, enrolled between 1996 and 2001 in the Carolina Breast Cancer Study. Self-reported NSAID use in the decade prior to diagnosis was categorized by duration and regularity of use. Differences in tumor size, stage, node, and receptor status by NSAID use were examined using Chi-square tests. Associations between NSAID use and breast cancer-specific mortality were examined using age- and race-adjusted Cox proportional hazards analysis. Tumor characteristics did not differ by NSAID use. Increased duration and regularity of NSAID use was associated with reduced breast cancer-specific mortality in women with ER-positive tumors (long-term regular use (≥8 days/month for ≥ 3 years) versus no use; hazard ratio (HR) 0.48; 95 % confidence interval (CI) 0.23-0.98), with a statistically significant trend with increasing duration and regularity (p-trend = 0.036). There was no association for ER-negative cases (HR 1.19; 95 %CI 0.50-2.81; p-trend = 0.891). Long-term, regular NSAID use in the decade prior to breast cancer diagnosis was associated with reduced breast cancer-specific mortality in ER-positive cases. If confirmed, these findings support the hypothesis that potential chemopreventive properties of NSAIDs are mediated, at least in part, through suppression of estrogen biosynthesis.

Different cellular p16(INK4a) localisation may signal different survival outcomes in head and neck cancer.

BACKGROUND: Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status. METHODS: Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS). RESULTS: A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20-82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status. CONCLUSION: Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status.

Adverse Urinary System Outcomes among Older Women with Endometrial Cancer.

PURPOSE OF THE STUDY: Endometrial cancer and its treatment may cause damage to the urinary system, but few large-scale studies have examined the incidence of urinary-related outcomes among endometrial cancer survivors. We investigated the risk of several urinary disease diagnoses among older women with endometrial cancer compared to women without a cancer history. METHODS: Women ages 66 years and older with an endometrial cancer diagnosis during 2004-2017 (N=44,386) and women without a cancer history (N=221,219) matched 5:1 on age, race/ethnicity, and state were identified in the Surveillance, Epidemiology, and End Results-Medicare linked data. ICD-9 and -10 diagnosis codes were used to identify urinary outcomes in the Medicare claims data. Cumulative incidences (IP) of urinary outcomes were estimated among women with and without endometrial cancer. Multivariable Cox proportional hazards regression models were used to estimate hazards ratios (HR) for urinary outcomes comparing women with and without endometrial cancer. HRs were also used to identify characteristics associated with urinary outcomes among endometrial cancer survivors. RESULTS: Relative to women without cancer, endometrial cancer survivors had an increased risk of urinary system diagnoses, including renal failure (5-year IP: 25% vs 14%; HR=1.50; 95% CI: 1.47-1.53), chronic kidney disease (5-year IP: 20% vs 14%; HR=1.25; 95% CI: 1.22-1.28), calculus of the urinary tract (5-year IP: 7% vs 4%; HR=1.55; 95% CI: 1.50-1.61), lower urinary tract infection (5-year IP: 55% vs 33%; HR=1.75; 95% CI: 1.72, 1.78), and bladder diseases (5-year IP: 10% vs 6%; HR=1.57; 95% CI: 1.52, 1.62). These associations persisted in analyses limited to 1+ and 5+ years after endometrial cancer diagnosis. Non-Hispanic Black or Hispanic race/ethnicity, higher comorbidity index, higher stage or grade cancer, non-endometrioid histology, and treatment with chemotherapy and/or radiation were often predictors of urinary outcomes among women with endometrial cancer. CONCLUSIONS: Our results suggest that, among older women, the risk of urinary outcomes is elevated after endometrial cancer. Monitoring for urinary diseases may be a critical part of long-term survivorship care for older women with an endometrial cancer history.

Birth weight and the incidence of childhood cancer.

The relationship of weight at birth to the occurrence of childhood cancer was studied with emphasis on the influence of age at diagnosis. Birth certificates for 681 children with cancer born in Washington State were linked with cancer registry data. Among children diagnosed with cancer during the first several years of life, there was an increased proportion with a high birth weight (greater than 4,000 g). The relationship was strongest for children under 2 years of age; about twice as many of them had high birth weights. However, the relationship was not present at all in those whose cancer was diagnosed at age 4 or older. This excess risk in young children associated with high birth weight was distributed among several types of cancer, including the two most common ones (leukemia and neuroblastoma).

Childhood brain tumors and paternal occupation in the aerospace industry.

Data from a case-control study of childhood brain tumors were analyzed to examine the possibility that paternal occupation in the aerospace industry is related to the development of a brain tumor in offspring. Parents of 51 children with brain tumors diagnosed in western Washington State during 1978-81 were interviewed, and their responses were compared to those of parents of 142 children selected at random from this population. Among all children, proportions of case and control fathers who had ever been employed in the aerospace industry were nearly identical [relative risk (RR) = 0.94; 95% confidence interval (CI) = 0.40-2.19]. Employment in the aerospace industry during the period from 1 year prior to birth to the time of diagnosis and any employment in the manufacturing part of the industry were not associated with increased risk. However, stratification by age at diagnosis revealed an increased risk associated with father's ever-employment in the industry (RR = 2.10; 95% CI = 0.79-5.60) for children under 10 years old. A corresponding decreased risk (RR = 0.12; 95% CI = 0.01-1.08) was found for children over 10 years old. Because of the relatively small number of cases with a positive paternal occupational history, interpretations of the difference in the direction of the association according to age at diagnosis must remain tentative ones.

Wilms' tumor and paternal occupation.

A case-control study was conducted to examine the relationship between Wilms' tumor and paternal occupational exposures. The case group consisted of 200 children diagnosed as having Wilms' tumor who were registered at selected National Wilms' Tumor Study institutions during the period June 1, 1984, to May 31, 1986. Disease-free controls were matched to each case using a random digit dialing procedure. The parents of cases and controls completed a self-administered questionnaire. There was no consistent pattern of increased risk for paternal occupational exposure to hydrocarbons or lead found in this study. However, certain paternal occupations were found to have an elevated odds ratio (OR) of Wilms' tumor, including vehicle mechanics, auto body repairmen, and welders. Offspring of fathers who were auto mechanics had a 4- to 7-fold increased risk of Wilms' tumor for all 3 time periods. The largest increased odds ratio for auto mechanics was in the preconception period [OR = 7.58; 95% confidence interval (CI) = 0.90-63.9]. Welders had a 4- to 8-fold increased odds ratio, with the strongest association during pregnancy (OR = 8.22; CI = 0.95-71.3). Although chance cannot be excluded as a possible explanation, association of Wilms' tumor with these occupations has been reported in previous studies. Further study is needed to provide data on the specific occupational exposures involved.

Alterations of the p16 gene in head and neck cancer: frequency and association with p53, PRAD-1 and HPV.

Alterations, especially homozygous deletions, of the putative tumor suppressor gene, p16 (p16INK4A, MTS1, CDKN2) have been found in tumor cell lines from a variety of neoplasms. Recent studies have reported frequent p16 gene deletions in cell lines from squamous cell carcinomas of the head and neck (SCCHN), although the prevalence of alterations was variable in primary tumors. This study determined the prevalence of point mutations and deletions of the p16 gene in 33 SCCHN. In addition, the association of p16 gene alterations and abnormalities of p53, PRAD-1 (cyclin D1), and the presence of human papillomavirus (HPV) was examined. We found an overall prevalence of p16 alterations of 36% (nine deletions, three single base substitutions, including one polymorphism). Seven tumors (of 29, 24%) had an alteration of p16 and p53; five (of 33, 15%) had alterations of p16 and PRAD-1; three (of 29, 10%) had alterations of all three genes. In addition, of the five tumors with human papillomavirus detected, only one also had a p16 gene alteration. The results indicate a potentially important role for the p16 gene in head and neck tumorigenesis. In addition, the presence of tumors with multiple somatic gene alterations suggest a possible interaction in the dysregulation of the cell cycle.

p53 mutations in head and neck cancer: new data and evaluation of mutational spectra.

It has been suggested that the frequency, type, and location of p53 mutations (mutational spectra) can be linked to specific exogenous and endogenous carcinogenic agents and processes. Squamous cell carcinoma of the head and neck (SCCHN) provides an excellent tumor model to evaluate the utility of the p53 mutational spectra, given that it has well-defined and strong risk factors (tobacco and alcohol). The purpose of this analysis was to establish the pattern of p53 mutations in SCCHN and evaluate this mutational spectrum in comparison to the spectra for other cancers with similar and different risk factors, including cancers of the esophagus, lung, and colon. p53 mutational data were obtained from head and neck tumors collected at the University of North Carolina Hospitals and the published literature. A total of 14 of 33 tumors from the University of North Carolina Hospitals (42%) were found to have a p53 mutation. The alterations included three transversions, seven transitions, two deletions, and two suspected codon 47 polymorphisms. In general, SCCHN and esophageal cancer share a similar mutational pattern in contrast to colon cancer. These two aerodigestive tract cancers were statistically different from lung cancer, despite sharing tobacco as a major risk factor. For example, G-->T transversions, a mutation type considered to be characteristic of exogenous DNA-damaging agents including tobacco smoke carcinogens, varied among tobacco-related cancer sites (14% SCCHN, 11% esophageal, and 31% lung) in contrast to colon cancer (6%). The comparison of mutational spectra for SCCHN and other cancers indicates that the effects of both tobacco and alcohol exposure may yield a pattern of p53 mutations that reflects elements of both exogenous and endogenous exposures.

GSTM1, GSTT1, GSTP1, CYP1A1, and NAT1 polymorphisms, tobacco use, and the risk of head and neck cancer.

Squamous cell carcinoma of the head and neck (SCCHN), including the oral cavity, pharynx, and larynx, provides an ideal tumor model to investigate gene-environment interaction. We conducted a hospital-based case-control study including 182 cases with newly diagnosed SCCHN and 202 controls with nonneoplastic conditions of the head and neck that required surgery. Lifetime tobacco use and risk of SCCHN were evaluated in relation to the polymorphisms of GSTM1, GSTT1, GSTP1, CYP1A1, and NAT1. The main effects of genotype were associated with a slightly increased risk of SCCHN for GSTP1 [age-, race-, and sex-adjusted odds ratio (OR), 1.2; confidence interval (CI), 0.8-1.9], GSTT1 (OR, 1.2; CI, 0.7-2.3), and NAT1 (OR, 1.1; CI, 0.7-1.7). The joint effects of genotype combinations showed some excess risk for the combination of the GSTM1 null genotype and the CYP1A1 Ile/Val polymorphism (OR, 2.6; CI, 0.7-10.3). The analysis of the joint effects (interaction) of the "at-risk" genotypes and tobacco use did not reveal any interaction on either the multiplicative or additive scale for GSTM1, GSTP1, or CYP1A1. However, there was a suggestion of an interaction on the additive scale between the pack-years of tobacco use and the GSTT1 null genotype. The combined heterozygote and homozygote NAT1*10 genotypes also had a suggestive interaction with tobacco smoking history. The results of this study suggest a possible gene-environment interaction for certain carcinogen metabolizing enzymes, but larger studies that fully evaluate the interaction are needed.

Parental smoking and alcohol consumption and risk of neuroblastoma.

Previous studies and animal evidence have suggested a relationship between parental tobacco or alcohol use and the risk of some childhood cancers, including neuroblastoma. A case-control study was conducted to investigate the relationship between parental tobacco smoking, alcohol consumption, and risk of neuroblastoma. Cases were children diagnosed with neuroblastoma over the period 1992-1994 at Children's Cancer Group and Pediatric Oncology Group institutions throughout the United States and Canada. One matched control was selected using random-digit dialing. Information on parental smoking and drinking history was obtained from 504 case and 504 control parents by telephone interview. Overall, there was no consistent pattern of association with parental smoking and alcohol consumption. For example, both maternal smoking and drinking during the period from 1 month before pregnancy through breastfeeding had adjusted odds ratios (ORs) of 1.1 [95% confidence interval (CI), 0.8-1.4]. There was no association with paternal smoking (OR, 1.2; 95% CI, 0.8-1.6) or paternal drinking 1 month before conception (OR, 1.0; 95% CI, 0.7-1.4). There was no consistent increase in risk by the amount of smoking or drinking during any time period relative to pregnancy. There was no suggestion of an increased risk when only one parent smoked. Smoking or drinking among both parents did not jointly increase the risk of neuroblastoma in their offspring. The child's age at diagnosis, stage, or MYCN oncogene amplification status did not materially alter the OR estimates. It is concluded that the results from this study do not indicate any evidence for a relationship between neuroblastoma and parental tobacco or alcohol use.

Glutathione S-transferase genotype as a susceptibility factor in smoking-related coronary heart disease.

Cancer studies suggest that the null polymorphisms of glutathione S-transferase M1 or T1 (GSTM1/GSTT1) may affect the ability to detoxify or activate chemicals in cigarette smoke. The potential modification of the association between smoking and coronary heart disease (CHD) by GSTM1 and GSTT1 has not been studied in humans. A case-cohort study was conducted to test the hypotheses that specific genotypes of GSTM1 or GSTT1 affect susceptibility to smoking-related CHD. CHD cases (n=400) accrued during 1987-1993 and a cohort-representative sample (n=924) were selected from a biracial cohort of 15792 middle-aged men and women in four US communities. A significantly higher frequency of GSTM1-0 and a lower frequency of GSTT1-0 were found in whites (GSTM1-0=47.1%, GSTT1-0=16.4%) than in African-Americans (AAs) (GSTM1-0=17.5%, GSTT1-0=25.9%). A smoking-GSTM1-0 interaction for the risk of CHD was statistically significant on an additive scale, with ever-smokers with GSTM1-0 at a approximately 1.5-fold higher risk relative to ever-smokers with GSTM1-1 and a approximately 2-fold higher risk relative to never-smokers with GSTM1-0, after adjustment for other CHD risk factors. The interaction between having smoked >/=20 pack-years and GSTT1-1 was statistically significant on both multiplicative and additive scales. The risk of CHD given both GSTT1-1 and >/=20 pack-years of smoking was approximately three times greater than the risk given exposure to >/=20 pack-years of smoking alone, and approximately four times greater than the risk given exposure to GSTT1-1 alone. The modification of the smoking-CHD association by GSTM1 or GSTT1 suggests that chemicals in cigarette smoke that are substrates for glutathione S-transferases may be involved in the etiology of CHD.

Pesticides and childhood cancers.

To evaluate the possible association between pesticides and the risk of childhood cancers, epidemiologic studies published between 1970 and 1996 were critically reviewed. Thirty-one studies investigated whether occupational or residential exposure to pesticides by either parents or children was related to increased risk of childhood cancer. In general, the reported relative risk estimates were modest. Risk estimates appeared to be stronger when pesticide exposure was measured in more detail. Frequent occupational exposure to pesticides or home pesticide use was more strongly associated with both childhood leukemia and brain cancer than either professional exterminations or the use of garden pesticides. Occupational pesticide exposure was also associated with increased risk of Wilms' tumor, Ewing's sarcoma, and germ cell tumors. Residence on a farm, a proxy for pesticide exposure, was associated with increased risk of a number of childhood cancers. Although increased risk of some childhood cancers in association with pesticide exposure is suggested by multiple studies, methodological limitations common to many studies restrict conclusions; these include indirect exposure classification, small sample size, and potential biases in control selection. Opportunities for methodologic improvement in future studies of pesticides and childhood cancers are described.

Workshop to identify critical windows of exposure for children's health: cancer work group summary.

We considered whether there are discrete windows of vulnerability in the development of cancer and which time periods may be of the greatest importance. Cancer was considered broadly, including cancers in childhood as well as adult cancers that may have an in utero or childhood origin. We concluded that there was evidence from animal and epidemiologic studies for causal relationships for preconceptional, in utero, and childhood exposures and cancer occurrence in children and adults. However, the evidence is incomplete and all relevant critical windows may not have been identified. The comprehensive evaluation of the relative importance of specific time windows of exposure is limited. Improvements in the design of epidemiologic studies and additional animal studies of mechanisms are warranted.

Nitrosatable drug exposure during pregnancy and adverse pregnancy outcome.

Recent investigations have suggested that drugs that are amines can undergo endogenous or exogenous nitrosation reactions to form N-nitroso compounds. These compounds have been extensively characterized in animal models as carcinogens, mutagens and teratogens. In order to examine the possible effects of exposure to nitrosatable drugs during gestation on pregnancy outcome, data were utilized from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. Pregnancy outcomes for 6061 pregnancies in which the mother ingested a drug known to undergo nitrosation were compared with 6921 randomly sampled pregnancies without such exposure. The major outcome factors of interest were birth defects, fetal, neonatal and infant death and birthweight. Our findings suggest that no significant increases in risk of fetal, neonatal and infant death or low birthweight were associated with nitrosatable drug exposure during pregnancy. However, the risk of a tumour in the offspring of exposed mothers was increased (relative risk, RR = 2.29; 95% Cl 0.99-5.26). Increases in relative risk of major malformations was also observed and this increase was greater when exposure during the first four months of pregnancy was examined separately (RR = 1.33; 1.11-1.58). There were specific individual malformations that were observed to have increased relative risks (for example: eye malformations, hydrocephaly, craniosynostosis and meningomyelocoele/meningocoele) but interpretation was difficult due to multiple comparisons and some of these observations were associated with wide confidence intervals. These types of adverse pregnancy outcomes were consistent with animal study outcomes.

Maternal exposure to N-nitrosatable drugs as a risk factor for childhood brain tumours.

BACKGROUND: Animal models suggest that compounds containing a nitrosyl group (N-nitroso compounds (NNO)) can act as potent transplacental carcinogens. Many common drug formulations have the potential to undergo nitrosation in vivo. The association between maternal use of nitrosatable drugs during pregnancy and development of brain tumours in the offspring was examined in a SEER-based case-control study. METHODS: Maternal exposure to nitrosatable drugs during pregnancy was compared among 361 childhood brain tumour cases and 1083 matched controls recruited through random-digit dialing. RESULTS: There was no increase in risk observed for childhood brain tumours overall (OR = 1.15; 95% CI: 0.69-1.94) or for astrocytomas individually (OR = 1.16; 95% CI: 0.50-2.69). A slight elevation in risk was noted for medulloblastomas (OR = 1.47; 95% CI: 0.28-7.62) and 'other' tumours (OR = 1.27; 95% CI: 0.56-2.86), however, both estimates were based on small numbers. CONCLUSIONS: Our findings suggest that no increased risk of childhood brain tumours was associated with maternal exposure to nitrosatable drugs. The study results should be viewed with caution given the imprecision of the point estimates as well as the lack of data on specific timing and dosage of exposure and degree of nitrosatability of drugs taken.

Cesarean birth and neonatal mortality in very low birth weight infants.

The authors attempted to relate neonatal mortality to method of delivery in a series of 345 infants, weighing 700 to 1500 g, who were born in King County, Washington, from 1977 to 1979. Overall, 38% of infants delivered vaginally died as opposed to 32% of those with cesarean births. However, after adjustment for birth weight, presentation, and place of delivery, cesarean birth was not associated with reduction in mortality. Even among those infants with a breech presentation, a group believed (on the basis of previous studies) to particularly benefit from cesarean birth, the data failed to show any mortality reduction. Based on the results of this study of very low birth weight singleton infants, it appears that the reduced neonatal mortality associated with cesarean birth, if present at all, is small in magnitude.

Wilms' tumor, overgrowth, and fetal growth factors: a hypothesis.

A hypothesis is advanced suggesting that the association between high birthweight, overgrowth features of certain congenital malformations, and Wilms' tumor may be due to the action of loci in addition to the putative Wilms' tumor locus on the short arm of chromosome #11. These genes include insulin, insulin-like growth factor II and the c-Ha-ras 1 oncogene. The possible role of environmental factors in the oncogenesis of Wilms' tumor is discussed.