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Breast Cancer Research
Published in: Breast Cancer Research 5/2005

Open Access 01-10-2005 | Research article

Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2mutation carriers

Authors: Joanne Kotsopoulos, Olufunmilayo I Olopade, Parviz Ghadirian, Jan Lubinski, Henry T Lynch, Claudine Isaacs, Barbara Weber, Charmaine Kim-Sing, Peter Ainsworth, William D Foulkes, Andrea Eisen, Ping Sun, Steven A Narod

Published in: Breast Cancer Research | Issue 5/2005

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Abstract

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.

Conclusion

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.
Appendix
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Literature
1.
Ford D, Easton DF, Stratton M, Narod S, Goldar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, et al: Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1998, 62: 676-689. 10.1086/301749.CrossRefPubMedPubMedCentral
2.
Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johansson O, Borg A, et al: Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003, 72: 1117-1130. 10.1086/375033.CrossRefPubMedPubMedCentral
3.
Narod S, Lynch H, Conway T, Watson P, Feunteun J, Lenoir G: Increasing incidence of breast cancer in family with BRCA1 mutation. Lancet. 1993, 341: 1101-1102. 10.1016/0140-6736(93)92468-9.CrossRefPubMed
4.
King MC, Marks JH, Mandell JB: Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003, 302: 643-646. 10.1126/science.1088759.CrossRefPubMed
5.
Foulkes WD, Brunet JS, Wong N, Goffin J, Chappuis PO: Change in the penetrance of founder BRCA1/2 mutations? A retrospective cohort study. J Med Genet. 2002, 39: 407-409. 10.1136/jmg.39.6.407.CrossRefPubMedPubMedCentral
6.
Narod SA: Modifiers of risk of hereditary breast and ovarian cancer. Nat Rev Cancer. 2002, 2: 113-123. 10.1038/nrc726.CrossRefPubMed
7.
Gayther SA, Warren W, Mazoyer S, Russell PA, Harrington PA, Chiano M, Seal S, Hamoudi R, van Rensburg EJ, et al: Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nat Genet. 1995, 11: 428-433. 10.1038/ng1295-428.CrossRefPubMed
8.
Gayther SA, Mangion J, Russell P, Seal S, Barfoot R, Ponder BA, Stratton MR, Easton D, et al: Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat Genet. 1997, 15: 103-105. 10.1038/ng0197-103.CrossRefPubMed
9.
10.
Rebbeck TR, Kantoff PW, Krithivas K, Neuhausen S, Blackwood MA, Godwin AK, Daly MB, Naraod SA, Garber JE, Lynch HT, et al: Modification of BRCA1-associated breast cancer risk by the polymorphic androgen-receptor CAG repeat. Am J Hum Genet. 1999, 64: 1371-1377. 10.1086/302366.CrossRefPubMedPubMedCentral
11.
Rebbeck TR, Wang Y, Kantoff PW, Krithivas K, Neuhausen SL, Godwin AK, Daly MB, Narod SA, Brunet JS, Vesprini D, et al: Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history. Cancer Res. 2001, 61: 5420-5424.PubMed
12.
Wang WW, Spurdle AB, Kolachana P, Bove B, Moden B, Ebbers SM, Suthers G, Tucker MA, Kaufman DJ, Doody MM, et al: A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers. Cancer Epidemiol Biomarkers Prev. 2001, 10: 955-960.PubMed
13.
Levy-Lahad E, Lahad A, Eisenberg S, Dagan E, Paperna T, Kasinetz L, Catane R, Kaufman B, Beller U, Renbaum B, et al: A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers. Proc Natl Acad Sci USA. 2001, 98: 3232-3236. 10.1073/pnas.051624098.CrossRefPubMedPubMedCentral
14.
Narod SA, Offit K: Prevention and management of hereditary breast cancer. J Clin Oncol. 2005, 23: 1656-1663. 10.1200/JCO.2005.10.035.CrossRefPubMed
15.
16.
Tannenbaum A: The dependence of tumor formation on the composition of the calorie-restricted diet as well as on the degree of restriction. 1945. Nutrition. 1996, 12: 653-654.CrossRefPubMed
17.
Friedenreich CM: Review of anthropometric factors and breast cancer risk. Eur J Cancer Prev. 2001, 10: 15-32. 10.1097/00008469-200102000-00003.CrossRefPubMed
18.
van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR, Fraser G, Goldbohm RA, Graham S, Kushi L, et al: Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol. 2000, 152: 514-527. 10.1093/aje/152.6.514.CrossRefPubMed
19.
Vainio H, Bianchini F, (Eds): Weight Control and Physical Activity. 2002, Lyons: IARC Press, 6: World Health Organization, International Agency for Research on Cancer: IARC Handbooks of Cancer Prevention
20.
Berglund G: Anthropometry, physical activity and cancer of the breast and colon. Nutrition and Lifestyle: Opportunities for Cancer Prevention. Edited by: Riboli EL. 2002, Lyons: IARC Scientific Publications, 231-241.
21.
Ballard-Barbash R: Anthropometry and breast cancer. Body size – a moving target. Cancer. 1994, 74 (3 Suppl): 1090-1100. 10.1002/1097-0142(19940801)74:3+<1090::AID-CNCR2820741518>3.0.CO;2-X.CrossRefPubMed
22.
Kumar NB, Lyman GH, Allen K, Cox CE, Schapira DV: Timing of weight gain and breast cancer risk. Cancer. 1995, 76: 243-249. 10.1002/1097-0142(19950715)76:2<243::AID-CNCR2820760214>3.0.CO;2-R.CrossRefPubMed
23.
24.
25.
Cullinane CA, Lubinski J, Neuhausen SL, Ghadirian P, Lynch HT, Isaacs C, Weber B, Moller P, Offit K, Kim-Sing C: Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers. Int J Cancer. 2005.
26.
WHO Expert Committee: Physical Status. The Use and Interpretation of Anthropometry. 1995, Geneva: World Health Organization
27.
Forbes GB, Reina JC: Adult lean body mass declines with age: some longitudinal observations. Metabolism. 1970, 19: 653-663. 10.1016/0026-0495(70)90062-4.CrossRefPubMed
28.
Ziegler RG: Anthropometry and breast cancer. J Nutr. 1997, 127 (5 Suppl): 924S-928S.PubMed
29.
Huang Z, Hankinson SE, Colditz GA, Stampfer MJ, Hunter DJ, Manson JE, Hennekens CH, Rosner B, Speizer FE, Willett WC, et al: Dual effects of weight and weight gain on breast cancer risk. JAMA. 1997, 278: 1407-1411. 10.1001/jama.278.17.1407.CrossRefPubMed
30.
Trentham-Dietz A, Newcomb PA, Egan KM, Titmus-Ernstoff L, Baron JA, Storer BE, Stampfer M, Willett WC: Weight change and risk of postmenopausal breast cancer (United States). Cancer Causes Control. 2000, 11: 533-542. 10.1023/A:1008961931534.CrossRefPubMed
31.
Feigelson HS, Jonas CR, Teras LR, Thun MJ, Calle EE: Weight gain, body mass index, hormone replacement therapy, and postmenopausal breast cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev. 2004, 13: 220-224. 10.1158/1055-9965.EPI-03-0301.CrossRefPubMed
32.
Cold S, Hansen S, Overvad K, Rose C: A woman's build and the risk of breast cancer. Eur J Cancer. 1998, 34: 1163-1174. 10.1016/S0959-8049(97)10167-8.CrossRefPubMed
33.
Frank TS, Deffenbaugh AM, Reid JE, Hulick M, Ward BE, Lingenfelter B, Gumpper KL, Scholl T, Tavtigian SV, Pruss DR, et al: Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol. 2002, 20: 1480-1490. 10.1200/JCO.20.6.1480.CrossRefPubMed
34.
Hilakivi-Clarke LA, Luoto R, Kinnunen T, Huttunen T, Gissler M, Koskenvuo M, Hemminki E: Pregnancy weight gain and mother's breast cancer risk. 93rd Annual Meeting of the American Association for Cancer Research, San Francisco, CA. 2002
35.
Mueller WH: The changes with age of the anatomical distribution of fat. Soc Sci Med. 1982, 16: 191-196. 10.1016/0277-9536(82)90022-3.CrossRefPubMed
36.
37.
Schapira DV, Kumar NB, Lyman GH, Cox CE: Abdominal obesity and breast cancer risk. Ann Intern Med. 1990, 112: 182-186.CrossRefPubMed
38.
Chang-Claude J, Becher H, Eby N, Gastert G, Wahrendorf J, Hamann U: Modifying effect of reproductive risk factors on the age at onset of breast cancer for German BRCA1 mutation carriers. J Cancer Res Clin Oncol. 1997, 123: 272-279.PubMed
39.
Kirschner MA, Ertel N, Schneider G: Obesity, hormones, and cancer. Cancer Res. 1981, 41: 3711-3717.PubMed
40.
Carroll KK: Obesity as a risk factor for certain types of cancer. Lipids. 1998, 33: 1055-1059. 10.1007/s11745-998-0305-8.CrossRefPubMed
41.
Potischman N, Swanson CA, Siiteri P, Hoover RN: Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J Natl Cancer Inst. 1996, 88: 756-758. 10.1093/jnci/88.11.756.CrossRefPubMed
42.
Henderson BE, Ross RK, Judd HL, Krailo MD, Pike MC: Do regular ovulatory cycles increase breast cancer risk?. Cancer. 1985, 56: 1206-1208. 10.1002/1097-0142(19850901)56:5<1206::AID-CNCR2820560541>3.0.CO;2-9.CrossRefPubMed
43.
Pike MC, Krailo MD, Henderson BE, Casagrande JT, Hoel DG: 'Hormonal' risk factors, 'breast tissue age' and the age-incidence of breast cancer. Nature. 1983, 303: 767-770. 10.1038/303767a0.CrossRefPubMed
44.
MacDonald PC, Edman CD, Hemsell DL, Porter JC, Siiteri PK: Effect of obesity on conversion of plasma androstenedione to estrone in postmenopausal women with and without endometrial cancer. Am J Obstet Gynecol. 1978, 130: 448-455.CrossRefPubMed
45.
Bruning PF, Bonfrer JM, Hart AA: Non-protein bound oestradiol, sex hormone binding globulin, breast cancer and breast cancer risk. Br J Cancer. 1985, 51: 479-484.CrossRefPubMedPubMedCentral
46.
Kaaks R: Nutrition, hormones, and breast cancer: is insulin the missing link?. Cancer Causes Control. 1996, 7: 605-625. 10.1007/BF00051703.CrossRefPubMed
47.
Stoll BA: Perimenopausal weight gain and progression of breast cancer precursors. Cancer Detect Prev. 1999, 23: 31-36. 10.1046/j.1525-1500.1999.00063.x.CrossRefPubMed
48.
Del Giudice ME, Fantus IG, Ezzat S, McKeown-Eyssen G, Page D, Goodwin PJ: Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat. 1998, 47: 111-120. 10.1023/A:1005831013718.CrossRefPubMed
49.
Campagnoli C, Biglia N, Belforte P, Botta D, Pedrini E, Sismondi P: Post-menopausal breast cancer risk: oral estrogen treatment and abdominal obesity induce opposite changes in possibly important biological variables. Eur J Gynaecol Oncol. 1992, 13: 139-154.PubMed
50.
Okosun IS, Liao Y, Rotimi CN, Prewitt TE, Cooper RS: Abdominal adiposity and clustering of multiple metabolic syndrome in White, Black and Hispanic Americans. Ann Epidemiol. 2000, 10: 263-270. 10.1016/S1047-2797(00)00045-4.CrossRefPubMed
51.
Evans DJ, Hoffmann RG, Kalkhoff RK, Kissebah AH: Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women. J Clin Endocrinol Metab. 1983, 57: 304-310.CrossRefPubMed
52.
Kaye SA, Folsom AR, Soler JT, Prineas RJ, Potter JD: Associations of body mass and fat distribution with sex hormone concentrations in postmenopausal women. Int J Epidemiol. 1991, 20: 151-156. 10.1093/ije/20.1.151.CrossRefPubMed
53.
Rose DP, Gilhooly EM, Nixon DW: Adverse effects of obesity on breast cancer prognosis, and the biological actions of leptin (review). Int J Oncol. 2002, 21: 1285-1292.PubMed
54.
Hu X, Juneja SC, Maihle NJ, Cleary MP: Leptin – a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst. 2002, 94: 1704-1711.CrossRefPubMed
55.
Verkasalo PK, Thomas HV, Appleby PN, Davey GK, Key TJ: Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom). Cancer Causes Control. 2001, 12: 47-59. 10.1023/A:1008929714862.CrossRefPubMed
56.
Moore JW, Key TJ, Bulbrook RD, Clark GM, Allen DS, Wang DY, Pike MC: Sex hormone binding globulin and risk factors for breast cancer in a population of normal women who had never used exogenous sex hormones. Br J Cancer. 1987, 56: 661-666.CrossRefPubMedPubMedCentral
57.
Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M: Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004, 363: 1346-1353. 10.1016/S0140-6736(04)16044-3.CrossRefPubMed
58.
Werner H, LeRoith D: The role of the insulin-like growth factor system in human cancer. Adv Cancer Res. 1996, 68: 183-223.CrossRefPubMed
59.
Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE: The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000, 21: 215-244. 10.1210/er.21.3.215.CrossRefPubMed
60.
Yu H, Rohan T: Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst. 2000, 92: 1472-1489. 10.1093/jnci/92.18.1472.CrossRefPubMed
61.
Klauwer D, Blum WF, Hanitsch S, Rascher W, Lee PD, Kiess W: IGF-I, IGF-II, free IGF-I and IGFBP-1, -2 and -3 levels in venous cord blood: relationship to birthweight, length and gestational age in healthy newborns. Acta Paediatr. 1997, 86: 826-833.CrossRefPubMed
62.
Ogilvy-Stuart AL, Hands SJ, Adcock CJ, Holly JM, Matthews DR, Mohamed-Ali V, Yudkin JS, Wilkinson AR, Dunger DB: Insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-1, growth hormone, and feeding in the newborn. J Clin Endocrinol Metab. 1998, 83: 3550-3557. 10.1210/jc.83.10.3550.CrossRefPubMed
63.
Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, Muller J, Hall K, Skakkebaek NE: Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab. 1994, 78: 744-752. 10.1210/jc.78.3.744.PubMed
64.
Okasha M, McCarron P, Gunnell D, Smith GD: Exposures in childhood, adolescence and early adulthood and breast cancer risk: a systematic review of the literature. Breast Cancer Res Treat. 2003, 78: 223-276. 10.1023/A:1022988918755.CrossRefPubMed
65.
Collaborative Group on Hormonal Factors in Breast Cancer: Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet. 2001, 358: 1389-1399. 10.1016/S0140-6736(01)06524-2.CrossRef
66.
Stunkard AJ, Albaum JM: The accuracy of self-reported weights. Am J Clin Nutr. 1981, 34: 1593-1599.PubMed
67.
Weaver TW, Kushi LH, McGovern PG, Potter JD, Rich SS, King RA, Whitbeck J, Greenstein J, Steller TA: Validation study of self-reported measures of fat distribution. Int J Obes Relat Metab Disord. 1996, 20: 644-650.PubMed
68.
Rimm EB, Stampfer MJ, Colditz GA, Chute CG, Litin LB, Willett WC: Validity of self-reported waist and hip circumferences in men and women. Epidemiology. 1990, 1: 466-473. 10.1097/00001648-199011000-00009.CrossRefPubMed
69.
Troy LM, Hunter DJ, Manson JE, Colditz GA, Stampfer MJ, Willett WC: The validity of recalled weight among younger women. Int J Obes Relat Metab Disord. 1995, 19: 570-572.PubMed
70.
Must A, Willett WC, Dietz WH: Remote recall of childhood height, weight, and body build by elderly subjects. Am J Epidemiol. 1993, 138: 56-64.CrossRefPubMed
71.
Stevens J, Keil JE, Waid LR, Gazes PC: Accuracy of current, 4-year, and 28-year self-reported body weight in an elderly population. Am J Epidemiol. 1990, 132: 1156-1163.CrossRefPubMed
72.
Casey VA, Dwyer JT, Coleman KA, Krall EA, Gardner J, Valadian I: Accuracy of recall by middle-aged participants in a longitudinal study of their body size and indices of maturation earlier in life. Ann Hum Biol. 1991, 18: 155-166. 10.1080/03014469100001492.CrossRefPubMed
Metadata
Title
Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2mutation carriers
Authors
Joanne Kotsopoulos
Olufunmilayo I Olopade
Parviz Ghadirian
Jan Lubinski
Henry T Lynch
Claudine Isaacs
Barbara Weber
Charmaine Kim-Sing
Peter Ainsworth
William D Foulkes
Andrea Eisen
Ping Sun
Steven A Narod
Publication date
01-10-2005
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2005
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1293

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