Prenatal DDT exposure and testicular cancer: a nested case-control study.

The authors examined maternal serum levels of DDT-related compounds in relation to son's risk of testicular cancer 30 years later. Fifteen of 9,744 live-born sons were diagnosed with germ cell testicular cancer and had maternal serum samples. Cases were matched to three controls on race and birth year. Maternal serum DDT-related compounds, measured in the early postpartum, were associated with her son's risk of testicular cancer. Despite low statistical power, we observed that mothers of cases had a significantly higher ratio of p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) to p,p'-DDE (1,1'-dichloro-2,2'-bis(p-chlorophenyl)ethylene) and lower o,p'-DDT (1,1,1-tricholoro-2-(p-chlororphenyl)-2-(o-chlorophenyl)ethane). These findings are consistent with earlier exposure to DDT and with slower p,p'-DDT elimination among mothers of cases. Whether these associations could be direct, or operate via other pathways is unknown. Further research on interindividual differences in DDT metabolism could provide clues to testicular cancer etiology.

Maternal smoking, alcohol, and coffee use during pregnancy and son's risk of testicular cancer.

It has been suggested that increased risk for testicular cancer occurring worldwide may be due to exposures during fetal development. Lifestyle or environmental exposures may be the most important predictors of risk. However, few studies have directly examined these exposures prospectively. The Child Health and Development Studies is a 40-year follow-up of 20,530 pregnancies occurring between 1959 and 1967. There were 20 cases of testicular cancer diagnosed through 2003 among sons with a maternal interview in early pregnancy. Cases were matched to three controls on birth year and race. Odds ratios and 95% confidence intervals were calculated with exact conditional logistic regression. Compared to controls, mothers of testicular cancer cases were more likely to drink alcohol (unadjusted odds ratio, 3.2; 95% confidence interval, 0.83-15.48 for above vs. below the median for controls) and less likely to drink coffee (unadjusted odds ratio, 0.19; 95% confidence interval, 0.02-1.02 for above vs. below the median). Case mothers were neither more nor less likely to smoke. Although low power may limit interpretation of negative results, the prospective design minimizes bias. In this cohort, maternal serum testosterone in pregnancy was previously reported to be lower in women who drank alcohol. Because populations with high testicular cancer risk also have lower maternal testosterone, we suggest that testosterone could play a role in explaining the higher risk of son's testicular cancer among mothers who drank alcohol during pregnancy.

Maternal smoking, alcohol consumption, and caffeine consumption during pregnancy in relation to a son's risk of persistent cryptorchidism: a prospective study in the Child Health and Development Studies cohort, 1959-1967.

The Child Health and Development Studies is a > or =40-year follow-up of 20,754 pregnancies occurring between 1959 and 1967 in California. There were 84 cases of undescended testes at birth persisting to at least age 2 years among 7,574 liveborn sons whose mothers were interviewed in early pregnancy. Cases were matched to three controls on birth year and race. Compared with mothers of controls, mothers of cryptorchid boys consumed more caffeine during pregnancy (odds ratio = 1.4, 95% confidence interval: 1.1, 1.9 for an interquartile range equivalent to three cups of coffee per day) but were not more likely to smoke or drink alcohol when all behaviors were considered together. Other maternal and perinatal risk factors were not significantly associated with persistent cryptorchidism and did not confound the association with caffeine.

Selected gene polymorphisms and their interaction with maternal smoking, as risk factors for gastroschisis.

BACKGROUND: Gastroschisis is a severe birth defect in which the infant is born with a portion of the intestines extruding through a small tear in the abdominal wall, usually to the right of the umbilical cord. Its etiology is unknown, but the prevailing hypothesis is that it results from a vascular accident at the time of involution of the right umbilical vein or of the development of the superior mesenteric artery. METHODS: In a case-control study of 57 cases of gastroschisis and 506 controls, we tested DNA for polymorphisms of 32 genes representing enzymes involved in angiogenesis, blood vessel integrity, inflammation, wound repair, and dermal or epidermal strength. RESULTS: In logistic regression, controlling for maternal ethnicity, and using the homozygote wild-type as referent, the following gene polymorphisms were associated with an increased risk for a gastroschisis for heterozygotes: ICAM1 gly241arg (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1 -3.4); NOS3 glu298asp (OR, 1.9; 95% CI, 1.1-3.4); NPPA 2238T > C (OR, 1.9; 95% CI, 1.0-3.4); and ADD1 gly460trp (OR, 1.5; 95% CI, 0.8-2.8). Additionally, for the NPPA and ADD1 single-nucleotide polymorphisms (SNPs), the homozygote variants had a significantly higher risk than the heterozygotes (OR, 7.5; 95% CI, 1.7-33.5 and OR, 4.9; 95% CI, 1.9-12.9, respectively). Three SNPs showed a strong interaction with maternal smoking. The risk for smokers with 1 or 2 variant alleles compared to nonsmokers with the wild-type allele were: NOS3 (OR, 5.2; 95% CI, 2.4-11.4); ICAM1 (OR, 5.2; 95% CI, 2.1-12.7); and NPPA (OR, 6.4; 95% CI, 2.8-14.6). CONCLUSIONS: These results support the hypothesis of a vascular compromise as part of a multifactorial etiology of gastroschisis involving both genes and environmental factors.

Maternal meiosis II nondisjunction in trisomy 21 is associated with maternal low socioeconomic status.

PURPOSE: We evaluated whether the association of socioeconomic risk factors for trisomy 21 differed by type of maternal meiotic error. METHODS: We determined meiotic errors by DNA analysis for 150 trisomy 21 cases, and maternal lifetime exposures to low socioeconomic factors by questionnaire. RESULTS: Mothers of meiosis II cases were significantly more likely to be exposed to four low socioeconomic factors than mothers of meiosis I cases (odds ratio = 9.50; 95% confidence interval = 1.8-49.8). CONCLUSION: Maternal lifetime exposure to poor socioeconomic environment is a risk factor for a trisomy 21, particularly if nondisjunction leads to a maternal meiosis II.

Fetal trisomy 21 and maternal preeclampsia.

BACKGROUND: Placental trophoblast shedding into maternal circulation has been hypothesized as a potential cause of preeclampsia. Because pregnancies with a trisomy 21 fetus also have high levels of fetal cells and cell-free fetal DNA in maternal circulation, we examined whether trisomy 21 pregnancies have a higher risk of preeclampsia than euploid pregnancies. METHODS: We used 2 population-based databases. We identified 7763 pregnancies with a singleton trisomy 21-affected fetus and 15,293 matched euploid gestations from the U.S. Natality files for the period 1995-1999. The second database consisted of 665 pregnancies with fetal trisomy 21 and 987 euploid controls in a population-based Down syndrome study in California. In the latter study, women were interviewed by telephone regarding characteristics and pregnancy complications. Gestational hypertension and preeclampsia are the outcomes of this study. RESULTS: The U.S. Natality files showed that in nulliparous women fetal trisomy 21 was associated with a reduced risk of pregnancy-induced hypertension (adjusted relative risk [aRR] = 0.67; 95% confidence interval [CI] = 0.53 to 0.85). Findings from the California study confirmed this association in nulliparous women, and further revealed that the decrease in overall risk of pregnancy-induced hypertension was mainly the result of a large reduction in the risk of preeclampsia (aRR = 0.19; CI = 0.04 to 0.88) rather than in gestational hypertension by itself (0.83; 0.37 to 1.84). Neither dataset showed these effects among multiparous pregnancies. CONCLUSION: Fetal trisomy 21 is associated with a reduced, rather than increased, risk of preeclampsia, specifically in nulliparous women.

Socioeconomic effects on the risk of having a recognized pregnancy with Down syndrome.

BACKGROUND: Appoximately 95% of Down syndrome (DS) cases are caused by an error in germ cell division (meiosis), resulting in an extra chromosome 21. The meiotic error, predominantly of maternal origin, occurs either during the mother's fetal life (meiosis I) or at ovulation (meiosis II). Because maternal-age-specific DS prevalence rates vary between and within populations, it has been hypothesized that environmental factors can affect the risk for a DS pregnancy. METHODS: In a population-based case-control study of 997 clinically recognized DS cases (including fetal losses) and 1007 controls without a birth defect, we examined the mother's socioeconomic status (SES) from the time of her fetal life to the time of conception. SES variables were considered as proxies for environmental factors. We used multiple logistic regression for the analyses. RESULTS: We found associations with low levels of each SES variable examined: mother's education less than high school (OR, 1.29; 95% CI, 1.01-1.65), father's low occupation (OR, 1.23; 95% CI, 0.95-1.60), father's low education (OR, 1.28; 95% CI, 0.99-1.64), mother's father's low occupation (OR, 1.35; 95% CI, 1.06-1.71), and family income <$20,000 (OR, 1.31; 95% CI, 1.02-1.68) [corrected]. The risk for DS increased as the number of low socioeconomic factors present throughout the mother's life increased. With four factors present, the risk (adjusted for confounders) almost doubled (OR, 1.98; 95% CI, 1.30-3.01). Those associations persisted among young (< 30) and old (> or = 30) maternal age groups. CONCLUSIONS: A mother's low SES during any period before conception increases her risk for a recognized pregnancy with DS. Because of the high birth prevalence of DS, the public health impact of maternal SES may be considerable.

DDT and DDE exposure in mothers and time to pregnancy in daughters.

Reproductive-tract anomalies after administration of the potent oestrogen, diethylstilboestrol, in pregnant women raised concerns about the reproductive effects of exposure to weakly oestrogenic environmental contaminants such as bis[4-chlorophenyl]-1,1,1-trichloroethane (p,p'-DDT) or its metabolites, such as bis[4-chlorophenyl]-1,1-dichloroethene (p,p'-DDE). We measured p,p'-DDT and p,p'-DDE in preserved maternal serum samples drawn 1-3 days after delivery between 1960 and 1963. We recorded time to pregnancy in 289 eldest daughters 28-31 years later. Daughters' probability of pregnancy fell by 32% per 10 microg/L p,p'-DDT in maternal serum (95% CI 11-48). By contrast, the probability of pregnancy increased 16% per 10 microg/L p,p'-DDE (6-27). The decreased fecundability associated with prenatal p,p'-DDT remains unexplained. We speculate that the antiandrogenic activity of p,p'-DDE may mitigate harmful androgen effects on the ovary during gestation or early life.

Prospective study of hepatitis C viral infection as a risk factor for subsequent B-cell neoplasia.

Several case-control studies have found increased prevalence of hepatitis C virus (HCV) in patients with non-Hodgkin lymphoma (NHL) and other B-cell lymphoproliferative disorders. We examined whether HCV infection preceded the development of these neoplasms in a prospective cohort study of 48 420 individuals in northern California. Stored sera from 95 subjects with NHL (n = 57), multiple myeloma (n = 24), or Hodgkin disease (n = 14) diagnosed a mean of 21 years after phlebotomy were screened for antibodies to HCV as well as viral RNA, based on previous reports of antibody-negative viremia. Sera from 4 cases and one of 95 age-, sex-, and race-matched controls were repeatedly reactive by enzyme immunoassay, but none were confirmed by recombinant immunoblot assay; none of the case sera had HCV RNA by reverse transcription- polymerase chain reaction. Although acquisition in later life cannot be ruled out, these prospective data do not support a substantial role of chronic HCV infection in the etiology of B-cell neoplasia.