Contraceptive use and the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation

Yue Yin Xia; Jacek Gronwald; Beth Karlan; Jan Lubinski; Jeanna M McCuaig; Jennifer Brooks; Pal Moller; Andrea Eisen; Sophie Sun; Leigha Senter; Louise Bordeleau; Susan L Neuhausen; Christian F Singer; Nadine Tung; William D Foulkes; Ping Sun; Steven A Narod; Joanne Kotsopoulos; Hereditary Ovarian Cancer Clinical Study Group

doi:10.1016/j.ygyno.2022.01.014

Contraceptive use and the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation

Gynecol Oncol. 2022 Mar;164(3):514-521. doi: 10.1016/j.ygyno.2022.01.014. Epub 2022 Jan 19.

Authors

Yue Yin Xia¹, Jacek Gronwald², Beth Karlan³, Jan Lubinski⁴, Jeanna M McCuaig⁵, Jennifer Brooks⁶, Pal Moller⁷, Andrea Eisen⁸, Sophie Sun⁹, Leigha Senter¹⁰, Louise Bordeleau¹¹, Susan L Neuhausen¹², Christian F Singer¹³, Nadine Tung¹⁴, William D Foulkes¹⁵, Ping Sun¹⁶, Steven A Narod¹⁷, Joanne Kotsopoulos¹⁸; Hereditary Ovarian Cancer Clinical Study Group

Collaborators

Hereditary Ovarian Cancer Clinical Study Group:
Rinat Yerushalmi, Robert Fruscio, Antonella Rastelli, Stefania Zovato, Zerin Hyder, Tomasz Huzarski, Cezary Cybulski, Kevin Sweet, Marie Wood, Wendy McKinnon, Christine Elser, Tuya Pal, Georgia Wiesner, Eitan Friedman, Wendy Meschino, Carrie Snyder, Kelly Metcalfe, Aletta Poll, Nicole Gojska, Ellen Warner, Raymond H Kim, Barry Rosen, Rochelle Demsky, Peter Ainsworth, Karen Panabaker, Linda Steele, Howard Saal, Kim Serfas, Seema Panchal, Carey A Cullinane, Robert E Reilly, Joanne L Blum, Ava Kwong, Cezary Cybulski, Daniel Rayson, Claudine Isaacs, Teresa Ramón Y Cajal, Jeffrey Dungan, Stephanie Cohen

Affiliations

¹ Women's College Research Institute, Women's College Hospital, 76 Grenville St., Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
² International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian, Pomeranian Medical University in Szczecin, Szczecin, Zachodniopomorskie, Poland.
³ David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
⁴ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁵ Familial Cancer Clinic, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
⁶ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁷ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
⁸ Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada.
⁹ British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
¹⁰ Division of Human Genetics, Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, OH, USA.
¹¹ Juravinski Cancer Centre, Department of Oncology, McMaster University, Hamilton, ON, Canada.
¹² Department of Population Sciences, City of Hope, Duarte, CA, USA.
¹³ Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
¹⁴ Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁵ Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada.
¹⁶ Women's College Research Institute, Women's College Hospital, 76 Grenville St., Toronto, ON, Canada.
¹⁷ Women's College Research Institute, Women's College Hospital, 76 Grenville St., Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
¹⁸ Women's College Research Institute, Women's College Hospital, 76 Grenville St., Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. Electronic address: joanne.kotsopoulos@wchospital.ca.

PMID: 35063280
DOI: 10.1016/j.ygyno.2022.01.014

Abstract

Background BRCA1 and BRCA2 (BRCA) mutation carriers face a high lifetime risk of developing ovarian cancer. Oral contraceptives are protective in this population; however, the impact of other types of contraception (e.g. intrauterine devices, implants, injections) is unknown. We undertook a matched case-control study to evaluate the relationship between type of contraception and risk of ovarian cancer among women with BRCA mutations. Methods A total of 1733 matched pairs were included in this analysis. Women were matched according to year of birth, date of study entry, country of residence, BRCA mutation type and history of breast cancer. Detailed information on hormonal, reproductive and lifestyle exposures were collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with each contraceptive exposure. Results Ever use of any contraceptive was significantly associated with reduced risk of ovarian cancer (OR = 0.62; 95% CI 0.52-0.75; P < 0.0001), which was driven by significant inverse associations with oral contraceptives (OR = 0.66; 95% CI 0.54-0.79; P < 0.0001) and contraceptive implants (OR = 0.30; 95% CI 0.12-0.73; P = 0.008). We observed a similar effect with use of injections (OR = 0.37; 95% CI 0.10-1.38; P = 0.14), but this did not achieve significance. No significant associations were observed between patterns of intrauterine device use and risk of ovarian cancer. Conclusions These findings support a protective effect of oral contraceptives and implants on risk of ovarian cancer among women with BRCA mutations. The possible protective effect of injections requires further evaluation.

Keywords: BRCA; Case-control; Contraception; Intrauterine device; Ovarian cancer.

MeSH terms

BRCA1 Protein / genetics
BRCA2 Protein / genetics
Breast Neoplasms* / genetics
Carcinoma, Ovarian Epithelial
Case-Control Studies
Contraceptives, Oral / therapeutic use
Female
Heterozygote
Humans
Mutation
Ovarian Neoplasms* / etiology
Ovarian Neoplasms* / genetics
Risk Factors

Substances

BRCA1 Protein
BRCA1 protein, human
BRCA2 Protein
BRCA2 protein, human
Contraceptives, Oral