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.

Survival in women with ovarian cancer with and without microsatellite instability.

PURPOSE OF INVESTIGATION: Microsatellite instability (MSI) is a hallmark of defective mismatch repair and is present in approximately 20% of ovarian cancers. It is not known if the presence of MSI predicts survival in women with epithelial ovarian cancer. MATERIALS AND METHODS: Cases of epithelial ovarian cancer were ascertained from a population-based study in Ontario and tumour samples were tested for MSI, using five MSI markers. Patients were divided into MSI-high and MSI-low/normal, according to National Cancer Institute criteria. The authors compared the prevalence of specific prognostic factors in the two subgroups, including age, grade, stage, and histology. They estimated the hazard ratio for death from ovarian cancer associated with MSI-high and with other prognostic factors using a multi-variate analysis. RESULTS: A total of 418 ovarian cancer patients were included. One hundred and twenty-seven (19.7%) cancers were MSI- high. Subgroup analyses did not reveal any statistically significant differences for pathologic features associated with MSI status. No survival difference was seen according to MSI status. CONCLUSIONS: The presence of MSI in ovarian cancer is not associated with survival.

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.

Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer.

BACKGROUND: Mutations in genes for hereditary non-polyposis colorectal cancer (HNPCC) in ovarian cancer patients remains poorly defined. We sought to estimate the frequency and characteristics of HNPCC gene mutations in a population-based sample of women with epithelial ovarian cancer. METHODS: The analysis included 1893 women with epithelial ovarian cancer ascertained from three population-based studies. Full-germline DNA sequencing of the coding regions was performed on three HNPCC genes, MLH1, MSH2 and MSH6. Collection of demographic, clinical and family history information was attempted in all women. RESULTS: Nine clearly pathogenic mutations were identified, including five in MSH6, two each in MLH1 and MSH2. In addition, 28 unique predicted pathogenic missense variants were identified in 55 patients. Pathogenic mutation carriers had an earlier mean age at diagnosis of ovarian cancer, overrepresentation of cancers with non-serous histologies and a higher number of relatives with HNPCC-related cancers. CONCLUSIONS: Our findings suggest that fewer than 1% of women with ovarian cancer harbour a germline mutation in the HNPCC genes, with overrepresentation of MSH6 mutations. This represents a lower-range estimate due to the large number of predicted pathogenic variants in which pathogenicity could not definitively be determined. Identification of mismatch repair gene mutations has the potential to impact screening and treatment decisions in these women.

Level-set segmentation of pulmonary nodules in megavolt electronic portal images using a CT prior.

PURPOSE: Pulmonary nodules present unique problems during radiation treatment due to nodule position uncertainty that is caused by respiration. The radiation field has to be enlarged to account for nodule motion during treatment. The purpose of this work is to provide a method of locating a pulmonary nodule in a megavolt portal image that can be used to reduce the internal target volume (ITV) during radiation therapy. A reduction in the ITV would result in a decrease in radiation toxicity to healthy tissue. METHODS: Eight patients with nonsmall cell lung cancer were used in this study. CT scans that include the pulmonary nodule were captured with a GE Healthcare LightSpeed RT 16 scanner. Megavolt portal images were acquired with a Varian Trilogy unit equipped with an AS1000 electronic portal imaging device. The nodule localization method uses grayscale morphological filtering and level-set segmentation with a prior. The treatment-time portion of the algorithm is implemented on a graphical processing unit. RESULTS: The method was retrospectively tested on eight cases that include a total of 151 megavolt portal image frames. The method reduced the nodule position uncertainty by an average of 40% for seven out of the eight cases. The treatment phase portion of the method has a subsecond execution time that makes it suitable for near-real-time nodule localization. CONCLUSIONS: A method was developed to localize a pulmonary nodule in a megavolt portal image. The method uses the characteristics of the nodule in a prior CT scan to enhance the nodule in the portal image and to identify the nodule region by level-set segmentation. In a retrospective study, the method reduced the nodule position uncertainty by an average of 40% for seven out of the eight cases studied.

Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis.

BACKGROUND: Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide. METHODS: We examined single nucleotide polymorphisms (SNPs) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) were genotyped using an Illumina assay. RESULTS: Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population [odds ratio, OR(BB vs AA) 2.81 (1.29-6.09), P=0.01] was also observed in a replication population, and the association remained suggestive in the combined analysis [OR(BB vs AA) 1.59 (1.08-2.34), P=0.02]. No other SNP associations remained suggestive in the replication populations. CONCLUSION: ABL1 has been implicated in multiple processes including cell division, cell adhesion and cellular stress response. These results suggest that characterization of the function of genetic variation in this gene in other ovarian cancer populations is warranted.

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.

Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the Ovarian Cancer Association Consortium pooled analysis.

There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case-control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3' variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95% CI=1.01-1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases; OR=0.80, 95% CI 0.62-1.04, P=0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer.

High expression of insulin-like growth factor binding protein-2 messenger RNA in epithelial ovarian cancers produces elevated preoperative serum levels.

The molecular etiology of epithelial ovarian cancer remains unclear. Using microarray expression analysis, we recently reported that expression of the insulin-like growth factor binding protein-2 (IGFBP-2) gene is elevated in advanced epithelial ovarian cancers. The aim of this study was to further delineate the role of IGFBP-2 in the pathoetiology of epithelial ovarian cancer and determine if elevated ovarian cancer IGFBP-2 gene expression is reflected in serum. Relative IGFBP-2 expression was measured using quantitative real-time polymerase chain reaction in 113 epithelial ovarian cancers and 6 normal ovarian surface epithelial samples. Preoperative serum IGFBP-2 levels were measured by radioimmunoassay in 84 women (42 ovarian cancers, 26 benign gynecological conditions, and 10 healthy female controls). Ovarian cancers demonstrated 38-fold higher mean IGFBP-2 expression than normal ovarian epithelium (P < 0.01). Serum IGFBP-2 levels were elevated in women with early- and advanced-stage ovarian cancer compared to controls and patients with benign gynecological conditions (P = 0.05 and P < 0.01, respectively). Epithelial ovarian cancers express high levels of IGFBP-2 relative to normal ovarian epithelium, and this is associated with elevated serum IGFBP-2 levels compared to both normal controls and patients with benign gynecological disease. Our findings provide further support that the insulin-like growth factor pathway plays a significant role in epithelial ovarian cancer pathogenesis. Further, IGFBP-2 may represent an additional serum biomarker with utility in detection and monitoring of epithelial ovarian cancer.

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.

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.

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.

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.