BACKGROUND: Familial clustering of age at onset would have implications for both personalized screening and aetiology, but has not been studied for breast cancer. METHODS: We prospectively studied a cohort of 23 145 sisters to explore whether their breast cancer risk changed near the age at diagnosis of a previously affected older sister. Using an age-time-dependent variable in a Cox regression model, we estimated hazard ratios for breast cancer when participants were near their sister's diagnosis age, relative to similarly aged women whose sister was diagnosed at a very different age. To rule out a correlation driven by young-onset familial cancer, we separately investigated women who had enrolled at age 50 or older. RESULTS: Of the 23 145 women, 1412 developed breast cancer during follow-up (median 9.5 years). The estimated hazard ratio was 1.80 (95% confidence interval: 1.18, 2.74) at their sister's age at diagnosis, suggesting a substantial increase in risk compared with women of the same age but whose sister was diagnosed at a very different age. Restriction to women who enrolled at or after age 50 produced similar results. CONCLUSIONS: This familial clustering suggests that there may be important genetic and/or early environmental risk factors that influence the timing of breast cancer, even when onset is late in life. Personalized screening might need to account for the age at which a sister was earlier diagnosed with breast cancer. Published by Oxford University Press on behalf of the International Epidemiological Association 2020. This work is written by US Government employees and is in the public domain in the US.
BACKGROUND: Familial clustering of age at onset would have implications for both personalized screening and aetiology, but has not been studied for breast cancer. METHODS: We prospectively studied a cohort of 23 145 sisters to explore whether their breast cancer risk changed near the age at diagnosis of a previously affected older sister. Using an age-time-dependent variable in a Cox regression model, we estimated hazard ratios for breast cancer when participants were near their sister's diagnosis age, relative to similarly aged women whose sister was diagnosed at a very different age. To rule out a correlation driven by young-onset familial cancer, we separately investigated women who had enrolled at age 50 or older. RESULTS: Of the 23 145 women, 1412 developed breast cancer during follow-up (median 9.5 years). The estimated hazard ratio was 1.80 (95% confidence interval: 1.18, 2.74) at their sister's age at diagnosis, suggesting a substantial increase in risk compared with women of the same age but whose sister was diagnosed at a very different age. Restriction to women who enrolled at or after age 50 produced similar results. CONCLUSIONS: This familial clustering suggests that there may be important genetic and/or early environmental risk factors that influence the timing of breast cancer, even when onset is late in life. Personalized screening might need to account for the age at which a sister was earlier diagnosed with breast cancer. Published by Oxford University Press on behalf of the International Epidemiological Association 2020. This work is written by US Government employees and is in the public domain in the US.
Entities:
Keywords:
Age at onset; age at diagnosis; breast cancer; heritability; sister study
Authors: Virginia Lope; Esther García-Esquinas; Beatriz Pérez-Gómez; Jone M Altzibar; Esther Gracia-Lavedan; María Ederra; Antonio José Molina de la Torre; Francisco Javier LLorca; Adonina Tardón; Víctor Moreno; Juan Bayo; Dolores Salas-Trejo; Rafael Marcos-Gragera; José Pumarega; Trinidad Dierssen-Sotos; Juan Pablo Barrio Lera; M A Concepción de Miguel Medina; Ignasi Tusquets; Pilar Amiano; Elena Boldo; Manolis Kogevinas; Nuria Aragonés; Gemma Castaño-Vinyals; Marina Pollán Journal: Cancer Epidemiol Date: 2015-11-21 Impact factor: 2.984
Authors: Alina V Brenner; Dale L Preston; Ritsu Sakata; Hiromi Sugiyama; Amy Berrington de Gonzalez; Benjamin French; Mai Utada; Elizabeth K Cahoon; Atsuko Sadakane; Kotaro Ozasa; Eric J Grant; Kiyohiko Mabuchi Journal: Radiat Res Date: 2018-07-25 Impact factor: 2.841