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Joellen M Schildkraut

Publications and source records attributed to Joellen M Schildkraut.

At least 19 recordsLinked to original sources
PubMed2025

Homologous Recombination Deficiency and Survival in Ovarian High-Grade Serous Carcinoma by Self-Reported Race.

BACKGROUND: Half of ovarian high-grade serous carcinomas (HGSC) have homologous recombination deficiency (HRD). However, HRD is not well characterized in Black individuals who experience worse survival after a diagnosis of HGSC. The objective of this study was to characterize ovarian HGSC HRD and examine its association with survival by self-reported race. METHODS: HRD features were identified using matched tumor-normal whole-exome and RNA sequencing in an HGSC cohort. We calculated age- and stage-adjusted HR and 95% confidence intervals (CI) for survival, comparing individuals with a feature to those without, separately by self-reported race. RESULTS: Any HRD was associated with a 32% reduced risk of death in Black individuals compared with a 62% reduction in White individuals (Black HR = 0.68; 95% CI, 0.43-1.09; White HR = 0.38; 95% CI, 0.14-1.04). More of the germline and somatic variants detected among Black individuals were unannotated or variants of uncertain significance (VUS; germline 65% vs. 45%; somatic 62% vs. 50%). Black individuals with germline unannotated/VUS were more likely to have tumors with HRD scarring and a first-degree family history of breast or ovarian cancer compared with those without (HRD scar 71.4% vs. 49.6%; family history 68.4% vs. 34.6%). CONCLUSIONS: HRD testing informs precision-based medicine approaches that improve outcomes, but a higher proportion of VUS among Black individuals may complicate referral for such care leading to worse outcomes for Black individuals. IMPACT: Our findings emphasize the importance of recruiting diverse individuals in genomics research and better characterizing VUS.

Adult↗
PubMed2006

Characterization of BRCA1 and BRCA2 mutations in a large United States sample.

PURPOSE: An accurate evaluation of the penetrance of BRCA1 and BRCA2 mutations is essential to the identification and clinical management of families at high risk of breast and ovarian cancer. Existing studies have focused on Ashkenazi Jews (AJ) or on families from outside the United States. In this article, we consider the US population using the largest US-based cohort to date of both AJ and non-AJ families. METHODS: We collected 676 AJ families and 1,272 families of other ethnicities through the Cancer Genetics Network. Two hundred eighty-two AJ families were population based, whereas the remainder was collected through counseling clinics. We used a retrospective likelihood approach to correct for bias induced by oversampling of participants with a positive family history. Our approach takes full advantage of detailed family history information and the Mendelian transmission of mutated alleles in the family. RESULTS: In the US population, the estimated cumulative breast cancer risk at age 70 years was 0.46 (95% CI, 0.39 to 0.54) in BRCA1 carriers and 0.43 (95% CI, 0.36 to 0.51) in BRCA2 carriers, whereas ovarian cancer risk was 0.39 (95% CI, 0.30 to 0.50) in BRCA1 carriers and 0.22 (95% CI, 0.14 to 0.32) in BRCA2 carriers. We also reported the prospective risks of developing cancer for cancer-free carriers in 10-year age intervals. We noted a rapid decrease in the relative risk of breast cancer with age and derived its implication for genetic counseling. CONCLUSION: The penetrance of BRCA mutations in the United States is largely consistent with previous studies on Western populations given the large CIs on existing estimates. However, the absolute cumulative risks are on the lower end of the spectrum.

Adult↗
PubMed2006

Analgesic drug use and risk of ovarian cancer.

BACKGROUND: Previous epidemiologic research suggests that analgesic use may reduce the risk of ovarian cancer, although results are not consistent. METHODS: In a population-based, case-control study, we analyzed data from 586 ovarian cancer cases and 627 matched controls in North Carolina for the relationship between analgesic use and ovarian cancer risk. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) while adjusting for potential confounders. RESULTS: Use of any nonsteroidal antiinflammatory drugs, including aspirin, within 5 years of diagnosis/interview was found to be associated with a reduction in the risk of ovarian cancer (adjusted OR = 0.72; 95% CI = 0.56-0.92). For use of acetaminophen, the OR was 0.78 (95% CI = 0.56-1.08). CONCLUSIONS: These data support an inverse relationship between the use of both nonsteroidal antiinflammatory drugs and acetaminophen and the risk of ovarian cancer.

Acetaminophen↗
PubMed2005

Anthropometric measurements and epithelial ovarian cancer risk in African-American and White women.

Previous studies of anthropometric factors and ovarian cancer risk have been inconsistent and none have evaluated the association among African-American women. Data from a population-based, case-control study of 593 cases and 628 controls were used to evaluate ovarian cancer risk in relation to weight, height, body mass index (BMI) and waist-to-hip ratio (WHR). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed and established risk factors were adjusted for using logistic regression models, stratified by race. Among all races, weight at age 18, WHR, weight and BMI one year prior to interview were associated with elevated ovarian cancer risk. When stratified by race, the association between WHR and ovarian was similar among Whites and among African Americans. However, African-American women in the fourth quartile of height had an elevated risk of ovarian cancer (OR = 3.2; 95% CI = 1.3-7.8), but this risk was not apparent in Whites (OR = 1.0; 95% CI = 0.7-1.4). These findings support the hypothesis that obesity is an important risk factor of ovarian cancer among African-Americans and Whites and also suggest that height may be a risk factor specific to African-Americans.

Adult↗
PubMed2005

Menopausal hormones and risk of ovarian cancer.

OBJECTIVE: The objective of this study was to determine if use of menopausal hormones was associated with ovarian cancer and if risk varied by type of hormone used. STUDY DESIGN: Data from a population-based, case-control study of ovarian cancer in North Carolina (364 cases, 370 controls, all postmenopausal) were analyzed to evaluate the relationship between menopausal hormones and ovarian cancer. Logistic regression analyses were used to calculate odds ratios (OR) and 95% CIs associated with various patterns of hormone use. RESULTS: Ovarian cancer cases were more likely than controls to report long-term use (>or=10 years) of unopposed estrogens (OR 2.2; 95% CI 1.2-4.1). No relationship was observed for estrogen always used with progestin. CONCLUSION: Hormone replacement therapy used according to current recommendations should not increase risk of ovarian cancer; however, clinicians should be aware of possible increased risk among women with a long history of estrogen replacement therapy.

Adult↗
PubMed2005

Transforming growth factor beta receptor I polyalanine repeat polymorphism does not increase ovarian cancer risk.

OBJECTIVES: It has been suggested that the 6A allele of the type I TGFbeta receptor (TGFbetaR1) polyalanine repeat tract polymorphism may increase susceptibility to various types of cancer including ovarian cancer. METHODS: The TGFbetaR1 polyalanine polymorphism was genotyped in 588 ovarian cancer cases and 614 controls from a population-based case-control study in North Carolina. RESULTS: Significant racial differences in the frequency of the 6A allele were observed between Caucasian (10.7%) and African-American (2.4%) controls (P < 0.001). One or two copies of the 6A allele of the TGFbetaR1 polyalanine polymorphism was carried by 18% of all controls and 19% of cases, and there was no association with ovarian cancer risk (OR = 1.07, 95% CI 0.80-1.44). The odds ratio for 6A homozygotes was 1.81 (95% CI 0.655.06), but these comprised only 0.98% of controls and 1.70% of cases. CONCLUSIONS: The 6A allele of the TGFbetaR1 polyalanine polymorphism does not appear to increase ovarian cancer risk. Larger studies would be needed to exclude the possibility that the small fraction of individuals who are 6A homozygotes have an increased risk of ovarian or other cancers.

Adult↗
PubMed2005

Antidepressant medication use [corrected] and risk of ovarian cancer.

OBJECTIVE: It has been hypothesized that antidepressants may enhance cancer growth. Previous studies of antidepressant use and ovarian cancer have been inconsistent and have been limited in their ability to examine the association with selective serotonin reuptake inhibitors (SSRIs), which are currently the antidepressants most commonly prescribed. The objective of this paper was to evaluate whether women with ovarian cancer were more likely to report past use of antidepressants than control women. METHODS: Antidepressant use was assessed in a population-based, case-control study of ovarian cancer (593 cases, 628 controls). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associated with antidepressant use overall and by subcategories of antidepressants. RESULTS: Antidepressant use was reported by 18% of cases and 20% of controls. No increased risk was observed for ever use of any type of antidepressant (OR 0.9, 95% CI 0.7-1.2) or for SSRIs (OR 1.0, 95% CI 0.7-1.5). There also was no evidence of increased risk with longer duration of use. Our study had greater than 80% power to detect an OR as small as 1.5. Thus, even a modest increase in risk associated with antidepressant use can be excluded with these data. CONCLUSION: Our study adds to the growing body of evidence suggesting that antidepressants do not have a significant effect on ovarian cancer risk. In particular, the data suggest that SSRIs, which are the most commonly used class of antidepressants, are not associated with an increased risk for ovarian cancer. LEVEL OF EVIDENCE: II-2.

Age Distribution↗
PubMed2005

Impact of the Cancer Risk Intake System on patient-clinician discussions of tamoxifen, genetic counseling, and colonoscopy.

The Cancer Risk Intake System (CRIS), a computerized program that "matches" objective cancer risks to appropriate risk management recommendations, was designed to facilitate patient-clinician discussion. We evaluated CRIS in primary care settings via a single-group, self-report, pretest-posttest design. Participants completed baseline telephone surveys, used CRIS during clinic visits, and completed follow-up surveys 1 to 2 months postvisit. Compared with proportions reporting having had discussions at baseline, significantly greater proportions of participants reported having discussed tamoxifen, genetic counseling, and colonoscopy, as appropriate, after using CRIS. Most (79%) reported CRIS had "caused" their discussion. CRIS is an easily used, disseminable program that showed promising results in primary care settings.

Adult↗
PubMed2005

IGF1 (CA)19 repeat and IGFBP3 -202 A/C genotypes and the risk of prostate cancer in Black and White men.

We investigated the relationship between the insulin-like growth factor-1 (IGF1) cytosine-adenine repeat (CA)(19) polymorphism located upstream of the gene's transcription start site, the insulin-like growth factor binding protein-3 (IGFBP3) -202 A/C promoter region polymorphism, and prostate cancer risk in Black and White men. Study subjects were U.S. veterans ages 41 to 75 years identified at the Durham Veterans Administration Medical Center over a 2.5-year period. Controls (n = 93) were frequency matched to cases (n = 100) based on race (Black or White) and age. Multivariable unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the associations between the polymorphisms and prostate cancer risk. For Blacks and Whites combined, an inverse association between prostate cancer and being homozygous for the most common IGF1 repeat allele, (CA)(19), (adjusted OR, 0.3; 95% CI, 0.1-0.7) was observed. Similar associations were noted for both Blacks (OR, 0.2; 95% CI, 0.0-0.8) and Whites (OR, 0.4; 95% CI, 0.1-1.6) separately. No statistically significant associations between the IGFBP3 C allele and prostate cancer were noted for Blacks (adjusted OR, 2.3; 95% CI, 0.8-6.2) or Whites (OR, 1.0; 95% CI, 0.3-3.1). The prevalence of the homozygous IGF1 (CA)(19) genotype was much lower in Black controls (21%) than White controls (46%), which may, in part, explain the increased prostate cancer incidence in Black versus White men. Further research is needed to confirm these findings.

Adult↗
PubMed2005

Estrogen bioactivation, genetic polymorphisms, and ovarian cancer.

Recent experimental evidence has shown that catechol estrogens can be activated through metabolism to form depurinating DNA adducts and thereby initiate cancer. Limited data are available regarding this pathway in epithelial ovarian cancer. We conducted a case-control study of 503 incident epithelial ovarian cancer cases at the Mayo Clinic in Rochester, MN, and Jacksonville, FL, and a 48-county region in North Carolina. Six hundred nine cancer-free controls were frequency matched to the cases on age, race, and residence. After an interview to obtain data on risk factors, a sample of blood was collected for DNA isolation. Subjects were genotyped for seven common single nucleotide polymorphisms in four genes involved in catechol estrogen formation (CYP1A1 and CYP1B1) or conjugation (COMT and SULT1A1). Data were analyzed using logistic regression, stratified by race, and with adjustment for design factors and potential confounders. None of the individual genotypes were significantly associated with ovarian cancer risk. However, an oligogenic model that considered the joint effects of the four candidate genes provided evidence for an association between combinations of these genes and ovarian cancer status (P = 0.015). Although preliminary, this study provides some support for the hypothesis that low-penetrance susceptibility alleles may influence risk of epithelial ovarian cancer.

Adult↗
PubMed2005

Epidemiology of intracranial meningioma.

Meningiomas are the most frequently reported primary intracranial neoplasms, accounting for approximately 25% of all such lesions diagnosed in the United States. Few studies have examined the risk factors associated with a diagnosis of meningioma with two categories of exposure, hormones (both endogenous and exogenous) and radiation, most strongly associated with meningioma risk. Limited data are also available on long-term outcomes for meningioma patients, although it is clear that the disease is associated with significant morbidity and mortality. Recent legislation passed in the United States (The Benign Brain Tumor Cancer Registries Amendment Act [H.R. 5204]) mandates registration of benign brain tumors such as meningioma. This will increase the focus on this disease over the coming years as well as likely increase the reported prevalence of the disease. The increased emphasis on research dedicated to the study of brain tumors coupled with the advent of new tools in genetic and molecular epidemiology make the current era an ideal time to advance knowledge for intracranial meningioma. This review highlights current knowledge of meningioma epidemiology and new directions for research efforts in this field.

Brain Neoplasms↗
PubMed2004

Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis.

OBJECTIVE: Women with endometriosis may be at an increased risk of ovarian cancer. It is not known whether reproductive factors that reduce the risk of ovarian cancer in general also reduce risk in women with endometriosis. We investigated whether the odds ratios for ovarian cancer that were associated with oral contraceptive use, childbearing, hysterectomy, and tubal ligation differ among women with and without endometriosis. STUDY DESIGN: We pooled information on the self-reported history of endometriosis from 4 population-based case-controlled studies of incident epithelial ovarian cancer, comprising 2098 cases and 2953 control subjects. We obtained data on oral contraceptive use, childbearing, breastfeeding, gynecologic surgical procedures, and other reproductive factors on each woman. Multivariable unconditional logistic regression was used to calculate odds ratios and 95% CI for ovarian cancer among women with endometriosis compared with women without endometriosis. Similar methods were used to assess the frequencies of risk factors among women with and without endometriosis. Adjustments were made for age, parity, oral contraceptive use, tubal ligation, family history of ovarian cancer, and study site. RESULTS: Women with endometriosis were at an increased risk of ovarian cancer (odds ratio, 1.32; 95% CI, 1.06-1.65). Using oral contraceptives, bearing children, and having a tubal ligation or hysterectomy were associated with a similar reduction in the odds ratios for ovarian cancer among women with and without endometriosis. In particular, the use of oral contraceptives for >10 years was associated with a substantial reduction in risk among women with endometriosis (odds ratio, 0.21; 95% CI, 0.08-0.58). CONCLUSION: Women with endometriosis are at an increased risk of epithelial ovarian cancer. Long-term oral contraceptive use may provide substantial protection against the disease in this high-risk population.

Adult↗
PubMed2004

Racial differences in enrolment in a cancer genetics registry.

BACKGROUND: Lower enrolment of minorities into research studies has been reported frequently. Most studies have little information about nonparticipants, making it difficult to identify characteristics associated with enrolment and how they might vary by race. METHODS: Women who had previously participated in a population-based, case-control study of breast cancer in North Carolina were invited to enroll in a cancer genetics registry. Detailed questionnaire data on sociodemographic characteristics and cancer risk factors were available for all women. We compared characteristics of women who agreed to be in the registry with those who were deceased, were unlocatable, or declined enrolment. Unconditional logistic regression analyses were done to identify predictors of enrolment. RESULTS: Enrolment rates were markedly lower among African Americans than Whites (15% and 36%, respectively) due to both lower contact rates (41% versus 63%) and lower enrolment rates among those contacted (37% versus 58%). Logistic regression models suggested that racial differences in enrolment were not due to socioeconomic characteristics or other cancer risk factors; race was the only significant predictor of enrolment in multivariable models (odds ratio 0.41, 95% confidence interval 0.23-0.72). CONCLUSIONS: Although all women had previously taken part in a research study, African American women were less likely to enroll in the cancer genetics registry than White women. A possible explanation of these findings is that studies of genetics may present particular concerns for African Americans. Further research is needed to identify attitudes and issues that present barriers to participation among minorities.

Adult↗
PubMed2004

Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers.

OBJECTIVE: The progestagenic milieu of pregnancy and oral contraceptive use is protective against epithelial ovarian cancer. A functional single nucleotide polymorphism in the promoter of the progesterone receptor (+331A) alters the relative abundance of the A and B isoforms and has been associated with an increased risk of endometrial and breast cancer. In this study, we sought to determine whether this polymorphism affects ovarian cancer risk. METHODS: The +331G/A polymorphism was genotyped in a population-based, case-control study from North Carolina that included 942 Caucasian subjects (438 cases, 504 controls) and in a confirmatory group from Australia (535 cases, 298 controls). Logistic regression analysis was used to calculate age-adjusted odds ratios (OR). RESULTS: There was a suggestion of a protective effect of the +331A allele (AA or GA) against ovarian cancer in the North Carolina study [OR, 0.72; 95% confidence interval (95% CI), 0.47-1.10]. Examination of genotype frequencies by histologic type revealed that this was due to a decreased risk of endometrioid and clear cell cancers (OR, 0.30; 95% CI, 0.09-0.97). Similarly, in the Australian study, there was a nonsignificant decrease in the risk of ovarian cancer among those with the +331A allele (OR, 0.83; 95% CI, 0.51-1.35) that was strongest in the endometrioid/clear cell group (OR, 0.60; 95% CI, 0.24-1.44). In the combined U.S.-Australian data that included 174 endometrioid/clear cell cases (166 invasive, 8 borderline), the +331A allele was significantly associated with protection against this subset of ovarian cancers (OR, 0.46; 95% CI, 0.23-0.92). Preliminary evidence of a protective effect of the +331A allele against endometriosis was also noted in control subjects (OR, 0.19; 95% CI, 0.03-1.38). CONCLUSIONS: These findings suggest that the +331G/A progesterone receptor promoter polymorphism may modify the molecular epidemiologic pathway that encompasses both the development of endometriosis and its subsequent transformation into endometrioid/clear cell ovarian cancer.

Adenocarcinoma, Clear Cell↗
PubMed2003

Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer.

PURPOSE: Because inherited BRCA1 or BRCA2 mutations strikingly increase ovarian cancer risk, polymorphisms in these genes could represent low penetrance susceptibility alleles. Previous studies of the BRCA2 N372H polymorphism suggested that HH homozygotes have a modestly increased risk of both breast and ovarian cancer. We have examined whether BRCA2 N372H or common amino acid-changing polymorphisms in BRCA1 predispose to ovarian cancer. EXPERIMENTAL DESIGN: A population-based, case control study of ovarian cancer was performed in North Carolina. Cases included 312 women with ovarian cancer (76% invasive and 24% borderline) and 401 age- and race-matched controls. Blood DNA from subjects was genotyped for BRCA2 N372H and BRCA1 Q356R and P871L. RESULTS: There was no association between BRCA2 N372H and risk of borderline or invasive epithelial ovarian cancer. The overall odds ratio (OR) for HH homozygotes was 0.8 [95% confidence interval (CI) = 0.4-1.5] and was similar in all subsets, including invasive serous cases. In addition, neither the BRCA1 Q356R (OR = 0.9, 95% CI 0.5-1.4) nor P871L (OR = 0.9, 95% CI 0.6-1.9) polymorphisms were associated with ovarian cancer risk. There was a significant racial difference in allele frequencies of the P871L polymorphism (P = 0.64 in Caucasians, L = 0.76 in African-Americans, P < 0.0001). CONCLUSIONS: In this population-based, case control study, common amino acid changing BRCA1 and 2 polymorphisms were not found to affect the risk of developing ovarian cancer.

Adenocarcinoma, Clear Cell↗
PubMed2003

Characterization of prediagnostic symptoms among primary epithelial ovarian cancer cases and controls.

OBJECTIVE: The goal of this study was to characterize types, frequency, combinations, and relative onset of symptoms among ovarian cancer cases and controls. METHODS: Participants were from an ongoing, population-based, case-control study of primary epithelial ovarian cancer in a 48-country region of North Carolina. Incident cases (N = 267), aged 20-74, were identified by area hospitals on a rapid case ascertainment basis between April 1999 and March 2001. Population-based controls, with at least one intact ovary, frequency matched on age and race, were identified using random-digit dialing (N = 287) and Health Care Financing Administration (HCFA) phone lists (N = 30). Trained nurse-interviewers, using a standardized questionnaire, asked participants about specific symptoms experienced for at least 2 weeks in the year prior to diagnosis (cases)/interview (controls). RESULTS: More than 90% of cases reported at least one symptom and symptoms were most often the reason for the doctor visit leading to diagnosis (74%), followed by routine examination (12%). Among invasive cases, symptoms with onsets longer before diagnosis (median 5-7 months) included gas/nausea/indigestion; urinary frequency/urgency; bowel irregularity; abnormal menstrual/vaginal bleeding or discharge; pain during intercourse; and ongoing fatigue. Symptoms with onsets closer to diagnosis (median of 2-4 months) included distended/hard abdomen; bloating/feeling of fullness; unexplained weight gain/loss; pelvic/abdominal discomfort; chest pain/respiratory difficulties; and "other" symptoms. Controls reported fewer symptoms than cases (median 1 vs 5 or 6). Control symptoms were of longer duration and much less likely to occur in combination. CONCLUSION: Earlier diagnosis of ovarian cancer may be possible if women and physicians recognize the importance of combinations of seemingly unrelated symptoms, especially those identified as occurring longer before diagnosis.

Adult↗
PubMed2002

Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk.

BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of developing ovarian cancer, but the mechanism for the risk reduction has not been well defined. In this study, we investigate the relationship between the progestin and estrogen potency in combination OCs and the risk of developing ovarian cancer. METHODS: The study included 390 case subjects with epithelial ovarian cancer and 2865 control subjects, between 20 and 54 years of age, identified from the Cancer and Steroid Hormone Study. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between ovarian cancer risk and combination OC formulations while controlling for potential confounders. All statistical tests were two-sided. RESULTS: With users of high-progestin/high-estrogen potency OC as the referent group, users of low-progestin/high-estrogen potency formulations (adjusted OR = 2.1; 95% CI = 1.2 to 3.7) and low-progestin/low-estrogen potency formulations (adjusted OR = 1.6; 95% CI = 0.9 to 3.0) had a higher risk of ovarian cancer than users of high-progestin/high-estrogen potency formulation. Low-progestin potency OC formulations were associated with a statistically significant higher risk than high-progestin potency formulations (adjusted OR = 2.2; 95% CI = 1.3 to 3.9). This association was seen even among users of short duration. CONCLUSION: The combination OC formulations with high-progestin potency appear to be associated with a greater reduction in ovarian cancer risk than those with low-progestin potency. Mechanisms underlying this reduction may include inhibition of ovulation and/or some direct biologic effects of the progestin.

Adult↗