New England-Based Case-Control Study of Ovarian Cancer

The case-control data provided to dbGaP were collected under NCI grant number CA54419 which had 3 enrollment phases: I (1992-1997), II (1998-2002) and III (2003-2008). Altogether, CA54419 funded 15 years of data and specimen collection, resulting in one of the longest running population based case-control studies of ovarian cancer. The study goal was to examine reproductive factors, lifestyle exposures, and genetic background in relation to ovarian cancer risk. The project recruited cases from Eastern Massachusetts and New Hampshire, and became known as the New England-based Case-Control study (NECC) of ovarian cancer.

3957 ovarian cancer cases diagnosed at ages 18-80 and residing in Eastern Massachusetts and New Hampshire were identified through tumor boards and registries. Of these, 3083 (78%) were eligible and among those eligible, 2203 (71%) were enrolled. After excluding 127 non-epithelial and 35 mixed mesodermal tumors, 2041 cases with epithelial tumors of ovarian, primary peritoneal, and fallopian tube origin, including borderline malignancies were included. On average, cases were interviewed 10 months after their diagnosis. A pathologist reviewed pathology reports and recorded histologic subtype, grade, and stage. Mixed ovarian cancers described as predominantly one type were classified as that type. Undifferentiated, transitional cell tumors, or mixed serous/transitional cell tumors were counted as serous. Other mixed epithelial, malignant Brenner, and unspecified epithelial tumors were classified as other.

2100 controls were identified through random digit dialing (RDD), driver-license lists, and town-resident lists. During the first funding phase from 1992 to 1997, 420 (72%) controls identified through RDD and 102 (51%) through town-resident lists agreed to participate. From 1998 to 2008, only town-resident lists were used to identify potential controls. 4366 controls were identified, of whom 1426 (33%) were ineligible if they had died, moved, or were seriously ill or if they did not have a working telephone, speak English, or have at least one ovary. Of eligible controls, 1362 (46%) declined to participate by phone or via 'opt-out' postcard and 1578 (54%) were enrolled. Controls were frequency matched to cases by 5-year age groups and region of residence.

In all phases, after written informed consent, demographic information, reproductive and medical history, and habits were assessed by in-person or telephone interview (in a few instances). All of the questions were framed with respect to a reference date defined as 1 year before the diagnosis date for women in the case group and the date of interview for those in the control group. This study was approved by institutional review boards at Dana Farber Harvard Cancer Center and Dartmouth Medical Center.

• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• Total number of consented subjects: 4141
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• MeSH

Cases with ovarian cancer were included if they resided in Eastern Massachusetts or New Hampshire during the study periods described above. Cases were ineligible if they had died, moved outside study area, did not have a working telephone number, or had a non-ovarian primary tumor. Non-epithelial cases were enrolled but were excluded from the analytic dataset.

Controls were eligible if they fell into frequency matched categories of age and residence as an enrolled case. Controls were ineligible if they had died, moved, or were seriously ill or if they did not have a working telephone, speak English, or have ovaries.

Between 1978 and 1981, Dr. Daniel Cramer supervised a case-control study of ovarian cancer as part of his Doctoral Thesis in Cancer Epidemiology. Dr. George Hutchinson was Dr. Cramer's thesis advisor and principal investigator (PI) of the case-control study of ovarian cancer. This study involved cases recruited from major teaching hospitals in greater Boston and controls selected from Town Lists of registered voters who were matched on age and residence precinct to the cases. A novel finding from this study was that use of talc powders in the genital area increases risk for ovarian cancer. The study also confirmed a lower risk associated with oral contraceptive use. With Dr. Cramer being the PI, a second Boston-based case-control study of ovarian cancer, similar to the first one, was performed between 1984 and 1987. This study confirmed the talc association, this time with much greater detail on the exposure, identified dairy product use to be a potential factor increasing risk, and suggested that psychotropic drug use might be linked to ovarian cancer risk. Because of limited exposure data, a narrow population base, and absence of stored DNA, data from these two studies are not being supplied to dbGaP. In 1992, with Dr. Cramer being the PI, the catchment area was enlarged to include all of Eastern Massachusetts and the entire state of New Hampshire using both hospital tumor boards and the Massachusetts and New Hampshire Cancer Registries. The New Hampshire component of the study was directed initially by Dr. Robert Greenberg and later by Dr. Linda Titus. The study was renewed in 1998 and again in 2003, and became one of the largest and longest running case-control studies of ovarian cancer sponsored by the National Cancer Institute. We believe that an attractive component of this study is the detailed data on demographic, anthropomorphic, lifestyle, and reproductive factors, from more than 2000 cases of epithelial ovarian cancer as well as extensive information on germ line genetic variants. The latter data was collected through our participation in the Ovarian Cancer Association Consortium. A subset of this data is being supplied to dbGaP which will allow linkage of the genetic data to our extensive "phenotypic" data. Our goal is to show that many well established risk factors for ovarian cancer, some of which are modifiable, including talc use, smoking, pregnancy and breastfeeding history, oral contraceptive use, ovulatory cycles, hysterectomy and tubal ligation, menopausal hormone use, and medical and family history, may be modified by particular genetic variants.

• Primary Phenotype: Ovarian Neoplasms

• Principal Investigator
  • Daniel W. Cramer, MD, ScD. Brigham and Women's Hospital, Boston, MA, USA.
• Funding Source
  • R01CA054419. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.