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PMID: 9326334 Published · ppublish English Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Interactions between genetic and reproductive factors in breast cancer risk in a French family sample.

American journal of human genetics ·Vol. 61 ·No. 3 ·1997-09-00 ·Pages 678-90

Andrieu N, Demenais F

Abstract

Considerable progress has been made in the characterization of the genetic component of breast cancer (BC). However, BC still remains a complex disease involving a genetic component and many other risk factors essentially linked to reproductive-life factors. To search for interactions between genetic and reproductive-life factors in the etiology of BC, a systematic family study was performed in two French hospitals from December 1987 to January 1990 and led to recruitment of 288 families, the IGRC data ("IGRC" refers to the Institut Gustave Roussy and Institut Curie, where the data were obtained). Detailed information on reproductive factors was recorded for probands and female first-degree relatives. Segregation analysis of BC was conducted by taking into account a variable age at onset of disease, by use of the class D regressive logistic model, as implemented in the REGRESS computer program. Segregation analyses of BC in IGRC data showed evidence for the segregation of a dominant gene and additional sister-sister dependence, both when reproductive factors were ignored and when they were included. A significant interaction was detected between the dominant gene and age when reproductive factors were taken into account. Among the reproductive factors included in segregation analysis, parity was found to interact with the dominant-gene effect, and there was an indication of an interaction, albeit not significant, between the dominant gene and age at menarche. Whereas the usual protective effect conferred on breast-cancer risk by high parity remained in nonsusceptible women, it disappeared in susceptible women. The increased BC risk associated with a late age at menarche was higher in susceptible women than in nonsusceptible women. Interactions between inherited predisposition to BC and reproductive factors were detected here for the first time by segregation analysis. It would be of major interest to confirm these results by family studies in other populations.

MeSH Terms
Abortion, Spontaneous Adult Age of Onset Aged Aged, 80 and over Breast Neoplasms/etiology,genetics Female France Genes, Dominant Humans Likelihood Functions Menarche Menopause Middle Aged Parity Pregnancy Regression Analysis Reproduction/physiology Risk Factors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Andrieu N
INSERM U. 351, Institut Gustave-Roussy, Villejuif, France.
Demenais F
References (64)
64 references, click to expand
  1. Family history of reproductive cancers and ovarian cancer risk: an Italian case-control study.
    Am J Epidemiol. 1992 Jan 1;135(1):35-40 PMID: 1736658
  2. Abortion, breast cancer, and epidemiology.
    N Engl J Med. 1997 Jan 9;336(2):127-8 PMID: 8988892
  3. Numerical comparisons of two formulations of the logistic regressive models with the mixed model in segregation analysis of discrete traits.
    Genet Epidemiol. 1992;9(6):419-35 PMID: 1487139
  4. Difficulty becoming pregnant and family history as interactive risk factors for postmenopausal breast cancer: the Iowa Women's Health Study.
    Cancer Causes Control. 1993 Jan;4(1):21-8 PMID: 8431527
  5. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium.
    Am J Hum Genet. 1993 Apr;52(4):678-701 PMID: 8460634
  6. Family history, age, and risk of breast cancer. Prospective data from the Nurses' Health Study.
    JAMA. 1993 Jul 21;270(3):338-43 PMID: 8123079
  7. Breast cancer: magnitude of the problem and descriptive epidemiology.
    Epidemiol Rev. 1993;15(1):7-16 PMID: 8405214
  8. An autologistic model for the genetic analysis of familial binary data.
    Am J Hum Genet. 1993 Oct;53(4):894-907 PMID: 8213818
  9. Segregation analysis of breast cancer from the cancer and steroid hormone study: histologic subtypes.
    J Natl Cancer Inst. 1990 Dec 19;82(24):1911-7 PMID: 2174465
  10. Linkage of early-onset familial breast cancer to chromosome 17q21.
    Science. 1990 Dec 21;250(4988):1684-9 PMID: 2270482
  11. A time-dependent logistic hazard function for modeling variable age of onset in analysis of familial diseases.
    Genet Epidemiol. 1990;7(6):391-407 PMID: 2292365
  12. Familial breast-ovarian cancer locus on chromosome 17q12-q23.
    Lancet. 1991 Jul 13;338(8759):82-3 PMID: 1676470
  13. Regressive logistic models for familial diseases: a formulation assuming an underlying liability model.
    Am J Hum Genet. 1991 Oct;49(4):773-85 PMID: 1897524
  14. Heterogeneity of the effect of family history on breast cancer risk.
    Epidemiology. 1991 Jul;2(4):276-84 PMID: 1912043
  15. Genetic epidemiology of breast cancer in Britain.
    Ann Hum Genet. 1991 May;55(Pt 2):151-9 PMID: 1952807
  16. Variations in the risk of breast cancer associated with a family history of breast cancer according to age at onset and reproductive factors.
    J Clin Epidemiol. 1993 Sep;46(9):973-80 PMID: 8263582
  17. A large kindred with 17q-linked breast and ovarian cancer: genetic, phenotypic, and genealogical analysis.
    J Natl Cancer Inst. 1994 Feb 2;86(3):200-9 PMID: 8283492
  18. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13.
    Science. 1994 Sep 30;265(5181):2088-90 PMID: 8091231
  19. Evidence for a third breast-cancer susceptibility gene.
    Lancet. 1994 Oct 22;344(8930):1151-2 PMID: 7934505
  20. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
    Science. 1994 Oct 7;266(5182):66-71 PMID: 7545954
  21. Accuracy of family cancer history in breast cancer patients.
    Eur J Cancer Prev. 1994 Jul;3(4):321-7 PMID: 7950886
  22. An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families. Breast Cancer Linkage Consortium.
    Am J Hum Genet. 1995 Jan;56(1):254-64 PMID: 7825586
  23. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium.
    Am J Hum Genet. 1995 Jan;56(1):265-71 PMID: 7825587
  24. Loss of heterozygosity and linkage analysis in breast carcinoma: indication for a putative third susceptibility gene on the short arm of chromosome 8.
    Oncogene. 1995 Mar 2;10(5):1023-6 PMID: 7898921
  25. Familial risk, abortion and their interactive effect on the risk of breast cancer--a combined analysis of six case-control studies.
    Br J Cancer. 1995 Sep;72(3):744-51 PMID: 7669588
  26. Complex segregation analysis of familial diseases with variable age of onset: comparison of different methods by a simulation study.
    Genet Epidemiol. 1995;12(3):231-49 PMID: 7557346
  27. The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues.
    Nat Genet. 1995 Sep;11(1):17-26 PMID: 7550308
  28. Genetic epidemiology of breast cancer: interest of survival analysis methods.
    Ann Hum Genet. 1995 Jul;59(Pt 3):271-82 PMID: 7486834
  29. Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence.
    Am J Hum Genet. 1995 Dec;57(6):1457-62 PMID: 8533776
  30. A critical look at methods for handling missing covariates in epidemiologic regression analyses.
    Am J Epidemiol. 1995 Dec 15;142(12):1255-64 PMID: 7503045
  31. Identification of the breast cancer susceptibility gene BRCA2.
    Nature. 1995 Dec 21-28;378(6559):789-92 PMID: 8524414
  32. Risk modifiers in carriers of BRCA1 mutations.
    Int J Cancer. 1995 Dec 20;64(6):394-8 PMID: 8550241
  33. Growth retardation and tumour inhibition by BRCA1.
    Nat Genet. 1996 Mar;12(3):298-302 PMID: 8589721
  34. A general model for the genetic analysis of pedigree data.
    Hum Hered. 1971;21(6):523-42 PMID: 5149961
  35. Sampling considerations in the gathering and analysis of pedigree data.
    Am J Hum Genet. 1979 Jan;31(1):62-9 PMID: 373427
  36. Family history of breast cancer as a risk indicator for the disease.
    Am J Epidemiol. 1980 Mar;111(3):301-8 PMID: 7361754
  37. Complex segregation analysis with pointers.
    Hum Hered. 1981;31(5):312-21 PMID: 7333620
  38. Interaction of familial and hormonal risk factors for breast cancer.
    J Natl Cancer Inst. 1982 Oct;69(4):817-22 PMID: 6956759
  39. A unified model for complex segregation analysis.
    Am J Hum Genet. 1983 Sep;35(5):816-26 PMID: 6614001
  40. Easy calculations of lod scores and genetic risks on small computers.
    Am J Hum Genet. 1984 Mar;36(2):460-5 PMID: 6585139
  41. Genetic epidemiology of breast cancer: segregation analysis of 200 Danish pedigrees.
    Genet Epidemiol. 1984;1(1):7-20 PMID: 6544234
  42. Familial breast cancer in a population-based series.
    Am J Epidemiol. 1986 Jan;123(1):15-21 PMID: 3940434
  43. Segregation analysis of the Jacobsen data.
    Genet Epidemiol Suppl. 1986;1:49-54 PMID: 3569870
  44. Examination of heterogeneity in 200 Danish breast cancer pedigrees.
    Genet Epidemiol Suppl. 1986;1:67-72 PMID: 3569873
  45. A genetic epidemiologic investigation of breast cancer in families with bilateral breast cancer. I. Segregation analysis.
    J Natl Cancer Inst. 1987 May;78(5):911-8 PMID: 3472000
  46. Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families.
    Proc Natl Acad Sci U S A. 1988 May;85(9):3044-8 PMID: 3362861
  47. Combined linkage and segregation analysis using regressive models.
    Am J Hum Genet. 1988 Jul;43(1):29-37 PMID: 3163888
  48. Possible heterogeneity in the segregation pattern of breast cancer in families with bilateral breast cancer.
    Genet Epidemiol. 1988;5(2):121-33 PMID: 3402724
  49. Genetic analysis of human breast cancer: implications for family study designs.
    Genet Epidemiol. 1988;5(4):225-33 PMID: 3169526
  50. Risk factors for breast cancer: pooled results from three Italian case-control studies.
    Am J Epidemiol. 1988 Dec;128(6):1207-15 PMID: 3195562
  51. Age at onset as an indicator of familial risk of breast cancer.
    Am J Epidemiol. 1990 Jun;131(6):961-72 PMID: 2188501
  52. The association of age and familial risk in a case-control study of breast cancer.
    Am J Epidemiol. 1990 Jun;131(6):973-83 PMID: 2343868
  53. BRCA1 is secreted and exhibits properties of a granin.
    Nat Genet. 1996 Mar;12(3):303-8 PMID: 8589722
  54. Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus.
    Nat Genet. 1996 Mar;12(3):309-11 PMID: 8589723
  55. Menstrual and reproductive factors and risk of breast cancer in Asian-Americans.
    Br J Cancer. 1996 Mar;73(5):680-6 PMID: 8605107
  56. Risk factors for breast cancer according to family history of breast cancer. For the Nurses' Health Study Research Group.
    J Natl Cancer Inst. 1996 Mar 20;88(6):365-71 PMID: 8609646
  57. Use of relatives of cases as controls to identify risk factors when an interaction between environmental and genetic factors exists.
    Int J Epidemiol. 1996 Jun;25(3):649-57 PMID: 8671569
  58. Does induced or spontaneous abortion affect the risk of breast cancer?
    Epidemiology. 1996 Sep;7(5):521-8 PMID: 8862985
  59. Menstrual patterns and breast cancer mortality in a large U.S. cohort.
    Epidemiology. 1996 Sep;7(5):543-6 PMID: 8862990
  60. Induced abortion, bias, and breast cancer: why epidemiology hasn't reached its limit.
    J Natl Cancer Inst. 1996 Dec 4;88(23):1698-700 PMID: 8943995
  61. Induced abortion and risk for breast cancer: reporting (recall) bias in a Dutch case-control study.
    J Natl Cancer Inst. 1996 Dec 4;88(23):1759-64 PMID: 8944006
  62. Induced abortion as an independent risk factor for breast cancer: a comprehensive review and meta-analysis.
    J Epidemiol Community Health. 1996 Oct;50(5):481-96 PMID: 8944853
  63. Induced abortion and the risk of breast cancer.
    N Engl J Med. 1997 Jan 9;336(2):81-5 PMID: 8988884
  64. Effect of family history, body-fat distribution, and reproductive factors on the risk of postmenopausal breast cancer.
    N Engl J Med. 1992 May 14;326(20):1323-9 PMID: 1565145
Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/515507
Published
1997-09-00
Pages
678-90
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1715946
Subset
IM
External Links
PubMed source DOI: 10.1086/515507 PMC Full Text View journal details
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