Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
BACKGROUND
Several anthropometric measures have been found to be associated with the risk of breast cancer. Current weight, body mass index, and adult weight gain appear to be predictors of postmenopausal breast cancer. These factors have been associated with a reduced risk of premenopausal breast cancer. We asked whether there is an association between changes in body weight and the risk of breast cancer in women who carry a mutation in either breast cancer susceptibility gene, BRCA1 or BRCA2.


METHODS
A matched case-control study was conducted in 1,073 pairs of women carrying a deleterious mutation in either BRCA1 (n = 797 pairs) or BRCA2 (n = 276 pairs). Women diagnosed with breast cancer were matched to control subjects by year of birth, mutation, country of residence, and history of ovarian cancer. Information about weight was derived from a questionnaire routinely administered to women who were carriers of a mutation in either gene. Conditional logistic regression was used to estimate the association between weight gain or loss and the risk of breast cancer, stratified by age at diagnosis or menopausal status.


RESULTS
A loss of at least 10 pounds in the period from age 18 to 30 years was associated with a decreased risk of breast cancer between age 30 and 49 (odds ratio (OR) = 0.47; 95% confidence interval (CI) 0.28-0.79); weight gain during the same interval did not influence the overall risk. Among the subgroup of BRCA1 mutation carriers who had at least two children, weight gain of more than 10 pounds between age 18 and 30 was associated with an increased risk of breast cancer diagnosed between age 30 and 40 (OR = 1.44, 95% CI 1.01-2.04). Change in body weight later in life (at age 30 to 40) did not influence the risk of either premenopausal or postmenopausal breast cancer.


CONCLUSIONS
The results from this study suggest that weight loss in early adult life (age 18 to 30) protects against early-onset BRCA-associated breast cancers. Weight gain should also be avoided, particularly among BRCA1 mutation carriers who elect to have at least two pregnancies.
Kotsopoulos
Joanne
J
Centre for Research in Women's Health, Women's College Hospital, University of Toronto, Toronto, ON, Canada. joanne.kotsopoulos@sw.ca
Olopado
Olufunmilayo I
OI
Ghadirian
Parviz
P
Lubinski
Jan
J
Lynch
Henry T
HT
Isaacs
Claudine
C
Weber
Barbara
B
Kim-Sing
Charmaine
C
Ainsworth
Peter
P
Foulkes
William D
WD
Eisen
Andrea
A
Sun
Ping
P
Narod
Steven A
SA
D000293:Adolescent; D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001835:Body Weight / Q000502:physiology*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D009154:Mutation; D012307:Risk Factors
D019313:BRCA1 Protein; D024682:BRCA2 Protein