# Understanding the role of ovulatory cycles on ovarian cancer risk across the lifecourse and spectrum of risk

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $46,936

## Abstract

PROJECT SUMMARY/ABSTRACT
Over 22,000 new cases of ovarian cancer are diagnosed in the United States each year, of whom only 47.6%
survive beyond five years. Ovarian is the most fatal of the gynecologic cancers, due to there being few
modifiable risk factors, no effective screening tool, a lack of specific symptoms, and a high probability of
recurrence. The only preventive guideline for ovarian cancer is for high-risk, pre-menopausal women
(BRCA1/2 carriers, or women with a family history of breast and/or ovarian cancer) to consider undergoing a
risk-reducing bilateral salpingo-oopherectomy after child bearing is complete. No official guidelines exist for
average-risk women. The etiology of the disease is poorly understood, yet, epidemiologic studies have
consistently found that events which interrupt ovulation are protective against ovarian cancer risk, leading to
the widely known “incessant ovulation” theory. Specifically, parity (higher number of live births), use of oral
contraceptives, and lactation are protective against ovarian cancer, while early age at menarche, late age at
menopause, infertility, and nulliparity have the opposite effect. However, the mechanisms through which the
initiation and frequency of ovulation influence cancer risk are unknown. One possibility is that the chance of
acquiring a cancer-causing mutation increases with each ovulatory cycle, due to inflammation during ovulation
that alters the microenvironment to promote DNA damage and seeding of cancer cells. Using two well-
characterized, large cohorts with deep phenotype, clinical, and genetic data (the United Kingdom Biobank and
Breast Cancer Family Registry), we will use a novel lifecourse epidemiologic approach to investigate how an
early life event (age at menarche) and long-term exposure (lifetime ovulatory cycles (LOC), a summary
measure that may better capture the accumulated exposure to ovulations than reproductive events considered
in isolation) relate to ovarian cancer. Specifically, we propose the following aims: 1) to assess whether the
effect of early age at menarche on risk of ovarian cancer is mediated by a high lifetime number of ovulations,
2) to evaluate gene-environment interaction between susceptibility genes and lifetime ovulatory cycles in
causing ovarian cancer, and 3) to elucidate the role of ovulations in ovarian cancer causation in a special
cohort of women at high risk due to a family history of breast and/or ovarian cancer. This will be the first study
to evaluate gene-environment interaction using LOC. The proposed training plan leverages my epidemiologic
training by adding cancer substantive knowledge and genomic data analysis skills such that I will be equipped
to address both the proposed aims and future research in the genetic bases of ovarian cancer. Execution of
these specific aims will advance the NCI's mission to understand the role of inherited mutations in combination
with lifestyle and environmental factors, here, in a lethal, ...

## Key facts

- **NIH application ID:** 10316162
- **Project number:** 5F31CA254030-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Diana Garofalo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,936
- **Award type:** 5
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316162

## Citation

> US National Institutes of Health, RePORTER application 10316162, Understanding the role of ovulatory cycles on ovarian cancer risk across the lifecourse and spectrum of risk (5F31CA254030-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10316162. Licensed CC0.

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