Abstract
Women with a BRCA1 mutation face a high lifetime risk of breast cancer. It is unknown to what extent environmental factors modify the inherent genetic risk. If women from different countries, but with similar mutations, experience different levels of cancer risk, nongenetic risk modifiers are likely to be present. Study subjects were a cohort of 1477 women with a BRCA1 mutation, from Canada (n = 358), the United States (n = 256) and Poland (n = 863). The women were followed for a mean of 4.3 years and 130 incident cases of breast cancer were recorded. Annual cancer incidence rates were calculated, and based on these, penetrance curves were constructed for women from North America and Poland. In a Cox proportional hazards model, residence in Poland, versus North America, was associated with an adjusted hazard ratio of 0.54 (95% CI 0.34-0.86; p = 0.01). The risk of breast cancer to age 70 was estimated to be 49% for women from Poland and 72% for women from North America. Among women with BRCA1 mutations, the risk of breast cancer in women who reside in Poland is less than that of women who reside in North America. The reasons for the difference are unknown, but this observation suggests that environmental factors or genetic modifiers are important in determining risk.
| Original language | English |
|---|---|
| Pages (from-to) | 229-234 |
| Number of pages | 6 |
| Journal | International Journal of Cancer |
| Volume | 131 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 1 2012 |
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All Science Journal Classification (ASJC) codes
- Cancer Research
- Oncology
Cite this
The risk of breast cancer in women with a BRCA1 mutation from North America and Poland. / Lubinski, Jan; Huzarski, Tomasz; Byrski, Tomasz; Lynch, Henry T.; Cybulski, Cezary; Ghadirian, Parviz; Stawicka, Malgorzata; Foulkes, William D.; Kilar, Ewa; Kim-Sing, Charmaine; Neuhausen, Susan L.; Armel, Susan; Gilchrist, Dawna; Sweet, Kevin; Gronwald, Jacek; Eisen, Andrea; Gorski, Bohdan; Sun, Ping; Narod, Steven A.
In: International Journal of Cancer, Vol. 131, No. 1, 01.07.2012, p. 229-234.Research output: Contribution to journal › Article
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TY - JOUR
T1 - The risk of breast cancer in women with a BRCA1 mutation from North America and Poland
AU - Lubinski, Jan
AU - Huzarski, Tomasz
AU - Byrski, Tomasz
AU - Lynch, Henry T.
AU - Cybulski, Cezary
AU - Ghadirian, Parviz
AU - Stawicka, Malgorzata
AU - Foulkes, William D.
AU - Kilar, Ewa
AU - Kim-Sing, Charmaine
AU - Neuhausen, Susan L.
AU - Armel, Susan
AU - Gilchrist, Dawna
AU - Sweet, Kevin
AU - Gronwald, Jacek
AU - Eisen, Andrea
AU - Gorski, Bohdan
AU - Sun, Ping
AU - Narod, Steven A.
PY - 2012/7/1
Y1 - 2012/7/1
N2 - Women with a BRCA1 mutation face a high lifetime risk of breast cancer. It is unknown to what extent environmental factors modify the inherent genetic risk. If women from different countries, but with similar mutations, experience different levels of cancer risk, nongenetic risk modifiers are likely to be present. Study subjects were a cohort of 1477 women with a BRCA1 mutation, from Canada (n = 358), the United States (n = 256) and Poland (n = 863). The women were followed for a mean of 4.3 years and 130 incident cases of breast cancer were recorded. Annual cancer incidence rates were calculated, and based on these, penetrance curves were constructed for women from North America and Poland. In a Cox proportional hazards model, residence in Poland, versus North America, was associated with an adjusted hazard ratio of 0.54 (95% CI 0.34-0.86; p = 0.01). The risk of breast cancer to age 70 was estimated to be 49% for women from Poland and 72% for women from North America. Among women with BRCA1 mutations, the risk of breast cancer in women who reside in Poland is less than that of women who reside in North America. The reasons for the difference are unknown, but this observation suggests that environmental factors or genetic modifiers are important in determining risk.
AB - Women with a BRCA1 mutation face a high lifetime risk of breast cancer. It is unknown to what extent environmental factors modify the inherent genetic risk. If women from different countries, but with similar mutations, experience different levels of cancer risk, nongenetic risk modifiers are likely to be present. Study subjects were a cohort of 1477 women with a BRCA1 mutation, from Canada (n = 358), the United States (n = 256) and Poland (n = 863). The women were followed for a mean of 4.3 years and 130 incident cases of breast cancer were recorded. Annual cancer incidence rates were calculated, and based on these, penetrance curves were constructed for women from North America and Poland. In a Cox proportional hazards model, residence in Poland, versus North America, was associated with an adjusted hazard ratio of 0.54 (95% CI 0.34-0.86; p = 0.01). The risk of breast cancer to age 70 was estimated to be 49% for women from Poland and 72% for women from North America. Among women with BRCA1 mutations, the risk of breast cancer in women who reside in Poland is less than that of women who reside in North America. The reasons for the difference are unknown, but this observation suggests that environmental factors or genetic modifiers are important in determining risk.
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U2 - 10.1002/ijc.26369
DO - 10.1002/ijc.26369
M3 - Article
C2 - 21834074
AN - SCOPUS:84860219652
VL - 131
SP - 229
EP - 234
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 1
ER -