Maternal vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years.

BACKGROUND/OBJECTIVE: Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring. SUBJECTS/METHODS: We conducted linear regressions to assess maternal plasma 25-hydroxyvitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10. RESULTS: Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l-m at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (-0.43 units; CI: -0.79, -0.07; P=0.02 for Q1 and -0.56 units; CI: -0.89, -0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing. CONCLUSIONS: Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.

Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

Newborns of obese parents have altered DNA methylation patterns at imprinted genes.

BACKGROUND: Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity. OBJECTIVE: We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT). METHODS: We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ⩾30 kg m(-2), was ascertained through standardized questionnaires. RESULTS: After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (ß=-2.57; s.e.=0.95; P=0.008), PEG3 (ß=-1.71; s.e.=0.61; P=0.005) and NNAT (ß=-3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: ß-coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR. CONCLUSION: We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood.

Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring.

OBJECTIVES: Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations. METHODS: Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions. RESULTS: After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (ß-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (ß-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight. CONCLUSION: We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

Factors associated with African Americans' enrollment in a national cancer genetics registry.

This study explored whether reactions to the Cancer Genetics Network (CGN) or CGN enrollment differed by receipt of a standard informational brochure versus a targeted version addressing factors previously associated with African Americans' health behavior decisions and research participation. The 262 participants, identified through tumor registries or clinic contacts, were mailed brochures and completed phone interviews. When asked whether - based on the brochure - they were or were not 'leaning toward' CGN enrollment, about 75% of both standard and targeted groups reported leaning toward. When given the opportunity at the end of the interview, 68% enrolled in the CGN. Trust was strongly related to enrollment. Less education, less satisfaction with cancer care, and individualistic rather than collective orientation were associated with lower trust. Education was also bivariately associated with enrollment, but mediation analysis indicated that the operational mechanism of education's influence on enrollment was through trust.

Progestin and estrogen potency of combination oral contraceptives and endometrial cancer risk.

OBJECTIVE: Using data from a case-control study of endometrial cancer, we investigated the relationship between the progestin and estrogen potency in combination oral contraceptives (OCs) and the risk of developing endometrial cancer. METHODS: Subjects included 434 endometrial cancer cases and 2,557 controls identified from the Cancer and Steroid Hormone (CASH) study. OCs were classified into four categories according to the individual potencies of each hormonal constituent (high versus low estrogen or progestin potency). Logistic regression was used to evaluate associations between endometrial cancer risk and combination OC formulations. RESULTS: With non-users as the referent group, use of OCs with either high potency progestin [odds ratio for endometrial cancer (OR)=0.21, 95% confidence interval (CI)=0.10 to 0.43] or with low potency progestin (OR=0.39, 95% CI=0.25 to 0.60) were both associated with a decreased risk of endometrial cancer. Overall high progestin potency OCs did not confer significantly more protection than low progestin potency OCs (OR=0.52, 95% CI=0.24 to 1.14). However, among women with a body mass index of 22.1 kg/m2 or higher, those who used high progestin potency oral contraceptives had a lower risk of endometrial cancer than those who used low progestin potency oral contraceptives (OR=0.31, 95% CI=0.11 to 0.92) while those with a BMI below 22.1 kg/m2 did not (OR=1.36, 95% CI=0.39 to 4.70). CONCLUSION: The potency of the progestin in most OCs appears adequate to provide a protective effect against endometrial cancer. Higher progestin-potency OCs may be more protective than lower progestin potency OCs among women with a larger body habitus.

Types and duration of symptoms prior to diagnosis of invasive or borderline ovarian tumor.

OBJECTIVE: The objective was to describe and compare types and duration of symptoms among women with invasive versus borderline ovarian tumors. METHODS: Cases were women, ages 20-69 years, diagnosed with invasive (616) and borderline (151) epithelial ovarian tumors from 1994 to 1998. Symptoms were obtained using a standardized in-person interview. Differences in types and duration of symptoms, time to diagnosis after consulting a physician, and primary reason for diagnosis by invasive/borderline status and histologic type were determined using bivariate and regression analyses controlling for age. RESULTS: Borderline and invasive cases reported similar types of symptoms. However, borderline cases were twice as likely to report not having had symptoms as invasive cases (16 vs 8%, P = 0.005). Prediagnostic symptom duration was longer among borderline versus invasive cases (median: 6 vs 4 months, P < 0.001). The median time from first consultation with a physician to diagnosis (1 month) did not differ by invasive/borderline status. Borderline cases were twice as likely to be diagnosed through routine examination as invasive cases (28 vs 16%, P = 0.001). Invasive cases were more likely to be diagnosed because of symptoms (62 vs 48%, P = 0.002). CONCLUSIONS: Because most (90%) women with ovarian tumors have symptoms and median symptom duration is 4 months, greater awareness of symptoms by women and physicians is needed for the earlier detection of ovarian tumors. The lesser likelihood of being detected by routine examination and the shorter symptom duration for invasive versus borderline cases underscores the need for effective screening and preventive strategies.

Age at natural menopause and the risk of epithelial ovarian cancer.

OBJECTIVE: To investigate the relationship between age at natural menopause and risk of developing epithelial ovarian cancer. METHODS: Using data from six population-based, case-control studies conducted in the United States, age at natural menopause among 1411 women with epithelial ovarian cancer and 6380 control subjects were analyzed using survival analysis methods, including Kaplan-Meier and proportional hazards models. Subjects ranged from 20 to 81 years of age. RESULTS: The median age at natural menopause was 50 years among cases compared with 51 years among controls, a difference of borderline statistical significance (P =.06). The hazard ratio for the relationship between case-control status and age at natural menopause was 1.09 (95% confidence interval 0.99, 1.20). Controlling for potential confounders including parity, oral contraceptive use, tubal ligation, smoking, and body mass index did not appreciably change this association. There was little evidence of an association between early age at natural menopause and early onset ovarian cancer (diagnosis age under 48 years). CONCLUSION: We observed a weak association between ovarian cancer risk and age at natural menopause and, among women with early onset disease, there was little evidence to suggest that early menopause is related to ovarian cancer. Thus, there seems little need for increased surveillance or screening for ovarian cancer among women with early natural menopause.

Early onset baldness and prostate cancer risk.

Prostatic carcinoma is the leading cancer among American men, yet few risk factors have been established. Although increased androgen levels have long been associated with both prostatic carcinoma and baldness, to date no studies have shown an association between hair patterning and prostate cancer risk. A lack of standardized instruments to assess baldness or the assessment of hair patterning during uninformative periods of time may have precluded the ability of previous studies to detect an association. We hypothesized that baldness, specifically vertex baldness, should be assessed using standardized instruments and during early adulthood if an association with prostate cancer risk is to be found. To test this hypothesis, we included identical items related to hair patterning in surveys that were administered in two distinct prostate cancer case-control studies (Duke-based study, n = 149; 78 cases; 71 controls and community-based study, n = 130; 56 cases; 74 controls). In each, participants were provided with an illustration of the Hamilton Scale of Baldness and asked to select the diagrams that best represented their hair patterning at age 30 and again at age 40. From these data, the following five categories were created and compared: not bald (referent group); vertex bald early onset (by age 30); vertex bald later onset (by age 40); frontal bald early onset (by age 30); frontal bald later onset (by age 40); and frontal (at age 30) to vertex bald (at age 40). Separate analyses of the two studies are consistent and suggest an association between vertex baldness and prostate cancer [vertex bald early onset odds ratios, 2.44 [confidence interval (CI), 0.57-10.46)] and 2.11 (CI, 0.66-6.73), respectively; vertex bald later onset odds ratios, 2.10 (CI, 0.63-7.00) and 1.37 (CI, 0.47-4.06), respectively]. Although statistical significance was not achieved in either one of these studies, the concordance between the data suggests a need for future studies to determine whether early onset vertex baldness serves as a novel biomarker for prostate cancer and whether androgen production, metabolism, or receptor status differs among these men when compared to those who exhibit other types of hair patterning.

Testing for hereditary breast and ovarian cancer in the southeastern United States.

OBJECTIVES: To detail characterization of mutations and uncharacterized variants in the breast cancer susceptibility genes BRCA1 and BRCA2, as observed in a population of breast cancer patients from the southeastern United States, and to examine baseline characteristics of women referred for counseling and testing and provide a preliminary look at how counseling and testing affected intentions toward prophylactic surgery. BACKGROUND: Mutations in the BRCA1 and BRCA2 genes give rise to a dramatically increased risk of developing breast or ovarian cancer or both. There are many reports about special populations in which deleterious mutations are present at a high frequency. It is useful to study these genes in more heterogeneous populations, reflecting different geographic regions. Interest in preventive surgery for gene carriers is high in women and their surgeons. METHODS: Women were recruited through a prospective clinical trial of counseling and free genetic testing. BRCA1 and BRCA2 were screened for mutations using standard techniques, and results were given to participants. Baseline questionnaires determined interest in preventive surgery at the beginning of the study. Follow-up questionnaires for those who completed testing surveyed interest in prophylactic surgery after counseling and receiving test results. RESULTS: Of 213 women who completed counseling and testing, 44 (20.6%) had 29 separate mutations; there were 11 Jewish women carrying three founder mutations. Twenty-eight women (13.1%) had uncharacterized variants in BRCA1 or BRCA2; nine were not previously reported. Women overestimated their chances of possessing a deleterious gene mutation compared to a statistical estimate of carrier risk. A number of women changed their intentions toward preventive surgery after genetic counseling and testing. CONCLUSIONS: Hereditary breast cancer due to mutations in BRCA1 and BRCA2 was a heterogeneous syndrome in the southeastern United States. Most mutations were seen just once, and uncharacterized variants were common and of uncertain clinical significance. In general, positive test results tended to reinforce intentions toward prophylactic surgery. In contrast, women not interested in surgery at the time of entry tended to remain reluctant after testing and counseling.

Cigarette smoking and epithelial ovarian cancer by histologic type.

OBJECTIVE: To examine cigarette smoking as a risk factor for different types of epithelial ovarian cancer. METHODS: We used data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case control investigation. Cases were 447 women aged 20-54 years with diagnoses of epithelial ovarian cancer. Controls were 3868 women selected by random-digit dialing. Conditional logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) as estimators of the relative risk of ovarian cancer. With age and study site as conditioning variables, OR point estimates were additionally adjusted for parity and use of oral contraceptives. RESULTS: The OR of mucinous epithelial ovarian cancer for women who had ever smoked was 2.3 (95% CI 1.4, 3.9) and for current smokers was 2.9 (95% CI 1.7, 4.9). The OR of mucinous tumors for current smokers was significantly elevated regardless of years since first cigarette or age at which women first smoked. The OR of mucinous tumors for current smokers increased slightly as cumulative pack-years of smoking increased, although the trend was not significant. Similar patterns of elevated risk were not observed among serous, endometrioid, or other histologic types. Odds ratio point estimates for former smokers were not significantly elevated for any histologic type. CONCLUSION: Current cigarette smoking was a risk factor for mucinous epithelial ovarian cancer, but not other histologic types.

Prognostic factors in early-onset epithelial ovarian cancer: a population-based study.

OBJECTIVE: To investigate the clinical prognostic factors that influence ovarian cancer survival in women with early-onset epithelial ovarian cancer using population-based data. METHODS: Subjects in the current study were from a population-based series of 197 patients with invasive ovarian cancer and 60 patients with ovarian cancer of low malignant potential who were identified from the Cancer and Steroid Hormone study. All subjects were between 20 and 54 years of age at diagnosis for ovarian cancer. Epidemiologic data were obtained from each participant. Immunohistochemical staining was performed to assess p53 expression in paraffin-embedded ovarian cancers. Univariate and multivariate analyses for survival were conducted using the proportional hazards model to test the prognostic significance of several clinicopathologic factors among subjects. RESULTS: Among women with invasive tumors, the proportional hazards model revealed that advanced stage at diagnosis [hazard ratio = 4.1, 95% confidence interval (CI) = 2.5, 6.6], age at diagnosis 46-54 (hazard ratio = 2.0, 95% CI = 1.3, 3.0), and overexpression of p53 (hazard ratio = 1.5, 95% CI = 1.1, 2.3) were significantly associated with decreased survival. CONCLUSION: These results provide evidence that stage, age, and p53 overexpression are independent predictors of decreased survival in women with invasive ovarian cancer diagnosed younger than age 55. Further investigation of the effect of age at diagnosis on the relationship between p53 overexpression and ovarian cancer survival is warranted.

Pregnancy recency and risk of ovarian cancer.

OBJECTIVE: A recent analysis suggested that ovarian cancer risk increased with time since last birth, possibly because of some aspect of pregnancy that affects the clearance of cells that have undergone malignant transformation. We analyzed data from four case-control studies pertaining to ovarian cancer risk in relation to age at first pregnancy, age at last pregnancy, and years since last pregnancy: 628 cases and 3432 neighborhood or population controls, ages 18-79, were included. METHODS: We used logistic regression to analyze associations between ovarian cancer risk, controlling for study, age (at diagnosis or corresponding reference age for controls), race, parity, oral contraceptive use, tubal ligation, family history of ovarian or breast cancer, and excluding women with a history of infertility. RESULTS: An early age at first pregnancy was associated with an increased risk of ovarian cancer (odds ratio 1.4, 95% confidence interval (1.1-1.8) for ages < or =19 compared to > or =25). Years since last pregnancy was also associated with increased ovarian cancer risk, with odds ratios of 1.4, 1.4, 1.8, and 2.1 for 10-14, 15-19, 20-24, and > or =25 years compared to 0-9 years (trend test p = 0.004), respectively. CONCLUSION: These observations support the results from the previous study, and raise additional questions about the role of pregnancy in the etiology of ovarian cancer.

Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk.

OBJECTIVE: To determine if blood levels of 25-hydroxyvitamin D (25-D) or its active metabolite, 1,25-dihydroxyvitamin D (1,25-D), are lower in women at the time of first diagnosis of breast cancer than in comparable women without breast cancer. DESIGN: This was a clinic-based case-control study with controls frequency-matched to cases on race, age, clinic and month of blood drawing. SETTING: University-based breast referral clinics. SUBJECTS: One hundred and fifty-six women with histologically documented adenocarcinoma of the breast and 184 breast clinic controls. RESULTS: There were significant mean differences in 1,25-D levels (pmol ml(-1)) between breast cancer cases and controls; white cases had lower 1,25-D levels than white controls (mean difference +/-SE: -11.08+/-0.76), and black cases had higher 1.25-D levels than black controls (mean difference +/-SE: 4.54+/-2.14), although the number of black women in the study was small. After adjustment for age, assay batch, month of blood draw, clinic and sample storage time, the odds ratio (95% confidence interval, CI) for lowest relative to highest quartile was 5.2 (95% CI 2.1, 12.8) for white cases and controls. The association in white women was stronger in women above the median age of 54 than in younger women, 4.7 (95% CI 2.1, 10.2) vs. 1.5 (95% CI 0.7, 3.0). There were no case-control differences in 25-D levels in either group. CONCLUSIONS: These data are consistent with a protective effect of 1,25-D for breast cancer in white women.

Prostate cancer: demographic and behavioral correlates of stage at diagnosis among blacks and whites in North Carolina.

OBJECTIVES: Although stage at diagnosis is one of the most important predictors of survival from prostate cancer, demographic factors, screening practices, and knowledge and beliefs associated with stage at diagnosis have not been well documented, particularly by race. METHODS: We conducted telephone interviews with 117 black and 114 white men diagnosed with prostate cancer to identify the demographic factors, healthcare-seeking behaviors, and prostate cancer-related knowledge, attitudes, and practices associated with stage. The sample was stratified by stage at diagnosis and was composed of men 50 to 74 years old who resided in a contiguous 63-county region in North Carolina and who were diagnosed at 1 of 16 participating hospitals. RESULTS: Among blacks, stage was inversely correlated with income (P = 0.04) and health insurance status (P < or = 0.001); among whites, stage was not associated with income or health insurance status, but approached significance with marital status (P = 0.06). Awareness of prostate cancer before diagnosis tended to decline with advancing stage among black men (P = 0.07), but was high for all stages (greater than 93%) among whites. Report of a prostate-specific antigen screen was inversely correlated with stage among black men (P = 0.01); a trend was observed among whites but was not significant (P = 0.20). Knowledge of prostate cancer risk factors was not significantly associated with stage for blacks or whites. Less than one third of men in each race and stage group knew that black men are at increased risk of prostate cancer. CONCLUSIONS: Demographic and other factors vary with stage and should be considered when designing and targeting interventions to reduce late diagnosis of prostate cancer.

Environmental contaminants and body fat distribution.

The effect of body mass index (BMI) and waist:hip ratio (WHR) on plasma levels of organochlorines [i.e., 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE)] was investigated in a sample of black and white women drawn from a population-based study in North Carolina. Organochlorine levels were determined in plasma samples from 99 women selected on the basis of race (black versus white) and quartile of the WHR (1st versus 4th). Of a panel of 20 organochlorine compounds tested, only DDE was detectable in most study subjects. Measurements of height, weight, and waist and hip circumferences were taken during an in-person interview. Information was elicited regarding dietary, residential, and breast-feeding histories. Results of multiple regression analyses indicate that black women had significantly higher plasma levels of DDE than white women. These levels were independent of BMI and WHR. BMI but not WHR was also found to be an independent predictor of DDE plasma level. These results suggest that black/white differences should be considered in studies that explore the relationship between environmental contaminants and various disease outcomes, such as breast cancer risk. In addition, BMI may affect circulating levels of contaminants and should also be considered a potentially important modifying factor for exposure to lipophilic substances.

Managing hereditary ovarian cancer risk.

Ovarian cancer is the fourth leading cause of cancer deaths in American women. About 10% of cases are thought to have a hereditary basis, and family history is the strongest known risk factor. In the past, prophylactic oophorectomy has been advocated for women with two or more affected first-degree relatives. More recently, with the identification of the genes responsible for most hereditary ovarian cancers (BRCA1, BRCA2), oophorectomy can now be offered specifically to women who are mutation carriers. Conversely, noncarriers in these families can be reassured that their risk of ovarian cancer is not increased. The value of oophorectomy in mutation carriers has not yet been proven, however, and concern exists that the benefit may be less than intuitively expected. First, although the lifetime risk of ovarian cancer initially was reported to be as high as 60%, more recent studies have suggested risks in the range of 15 to 30%. A better understanding of the factors that underlie variable penetrance in mutation carriers is needed to augment our ability to counsel individual women. In addition, peritoneal papillary serous carcinoma indistinguishable from ovarian cancer occurs in some women after oophorectomy. Studies that better define the frequency with which this occurs are needed to establish the magnitude of the protective effect conferred by prophylactic oophorectomy. In view of the uncertainty regarding the efficacy of prophylactic oophorectomy, chemopreventive and early detection approaches also deserve consideration as strategies for decreasing ovarian cancer mortality in women who carry mutations in ovarian cancer susceptibility genes.

Treatment options, selection, and satisfaction among African American and white men with prostate carcinoma in North Carolina.

BACKGROUND: In the U.S., prostate carcinoma mortality is greatest among African Americans. In North Carolina, the state with the fourth largest population of African Americans, the prostate carcinoma mortality rate is 2.5 times greater among African Americans than among whites and is the highest reported rate for any state in the nation. To explore potential reasons for the racial differential in mortality, a study was undertaken to determine whether differences related to treatment existed between African American and white men who were diagnosed with prostate carcinoma during the period 1994-1995. METHODS: Cases were selected from 16 institutions within a region comprising 63 contiguous counties where the overall population was >20% African American. A stratified design was employed to accrue subjects into groups of even size according to race and disease stage (n = 231). A telephone survey was conducted, which assessed treatment options discussed by patients with their physicians, treatment(s) received, factors influencing treatment, satisfaction with treatments discussed and options given, and sociodemographic information. RESULTS: All measures related to treatment were consistently associated with stage at diagnosis (P < 0.001) rather than other variables measured (i.e., race, age, income, comorbidity, education, and residential status). Furthermore, most subjects reported that their physicians presented several treatment options (65%), that they were satisfied with the options presented (90%), and that the physician was the most important factor influencing their treatment decision (57%). CONCLUSIONS: These data suggest that African American and white men in North Carolina receive comparable treatment for prostate carcinoma. Therefore, efforts to reduce the racial disparity in mortality should be directed toward lessening the high incidence of later stage disease at diagnosis and exploring potential biologic differences that may increase the risk of more aggressive disease among African Americans.