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Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study

Summary Background Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene–environment int... Full description

Journal Title: Lancet 2010, Vol.375 (9732), p.2143-2151
Main Author: Travis, Ruth C, Dr
Other Authors: Reeves, Gillian K, PhD , Green, Jane, MD , Bull, Diana , Tipper, Sarah J, MSc , Baker, Krys , Beral, Valerie, Prof , Peto, Richard, Prof , Bell, John, Prof , Zelenika, Diana, PhD , Lathrop, Mark, Prof
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
Publisher: Kidlington: Elsevier Ltd
ID: ISSN: 0140-6736
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title: Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study
format: Article
creator:
  • Travis, Ruth C, Dr
  • Reeves, Gillian K, PhD
  • Green, Jane, MD
  • Bull, Diana
  • Tipper, Sarah J, MSc
  • Baker, Krys
  • Beral, Valerie, Prof
  • Peto, Richard, Prof
  • Bell, John, Prof
  • Zelenika, Diana, PhD
  • Lathrop, Mark, Prof
subjects:
  • Abridged Index Medicus
  • Adenine
  • Age Factors
  • Alcohol Drinking
  • Articles
  • Ataxia Telangiectasia Mutated Proteins
  • Biological and medical sciences
  • Body Height
  • Body Mass Index
  • Breast cancer
  • Breast Feeding
  • Breast Neoplasms - etiology
  • Breast Neoplasms - genetics
  • Caspase 8 - genetics
  • Cell Cycle Proteins - genetics
  • Cytosine
  • Data collection
  • DNA-Binding Proteins - genetics
  • Environment
  • Environment. Living conditions
  • Female
  • General aspects
  • Genetic aspects
  • Genetic polymorphisms
  • Genotype
  • Gynecology. Andrology. Obstetrics
  • Health services
  • Hormone Replacement Therapy
  • Humans
  • Internal Medicine
  • Leucine Zippers - genetics
  • Mammary gland diseases
  • MAP Kinase Kinase Kinase 1 - genetics
  • Medical research
  • Medical sciences
  • Menarche - physiology
  • Menopause - physiology
  • Microfilament Proteins - genetics
  • Middle Aged
  • Parity
  • Phosphatidylinositol 3-Kinases - genetics
  • Phosphoproteins - genetics
  • Polymorphism, Genetic - genetics
  • Pregnancy
  • Prospective Studies
  • Protein-Serine-Threonine Kinases - genetics
  • Public health. Hygiene
  • Public health. Hygiene-occupational medicine
  • Receptor, Fibroblast Growth Factor, Type 2 - genetics
  • Receptors, Progesterone - genetics
  • Risk Factors
  • Transforming Growth Factor beta1 - genetics
  • Tumor Suppressor Proteins - genetics
  • Tumors
  • Variables
  • Womens health
  • Young Adult
ispartof: Lancet, 2010, Vol.375 (9732), p.2143-2151
description: Summary Background Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene–environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. Methods We tested gene–environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms ( FGFR2 -rs2981582, TNRC9 -rs3803662, 2q35-rs13387042, MAP3K1 -rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8 -rs1045485, LSP1 -rs3817198, 5q-rs30099, TGFB1 -rs1982073, and ATM -rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). Findings After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene–environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1 -rs889312 were significantly shorter than non-carriers (mean height 162·4 cm [95% CI 162·1–162·7] vs 163·1 cm [162·9–163·2]; p=0·01 after allowance for multiple testing). Interpretation Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. Funding Cancer Research UK and the UK Medical Research Council.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
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titleGene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study
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creatorTravis, Ruth C, Dr ; Reeves, Gillian K, PhD ; Green, Jane, MD ; Bull, Diana ; Tipper, Sarah J, MSc ; Baker, Krys ; Beral, Valerie, Prof ; Peto, Richard, Prof ; Bell, John, Prof ; Zelenika, Diana, PhD ; Lathrop, Mark, Prof
creatorcontribTravis, Ruth C, Dr ; Reeves, Gillian K, PhD ; Green, Jane, MD ; Bull, Diana ; Tipper, Sarah J, MSc ; Baker, Krys ; Beral, Valerie, Prof ; Peto, Richard, Prof ; Bell, John, Prof ; Zelenika, Diana, PhD ; Lathrop, Mark, Prof ; for the Million Women Study Collaborators ; Million Women Study Collaborators
descriptionSummary Background Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene–environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. Methods We tested gene–environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms ( FGFR2 -rs2981582, TNRC9 -rs3803662, 2q35-rs13387042, MAP3K1 -rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8 -rs1045485, LSP1 -rs3817198, 5q-rs30099, TGFB1 -rs1982073, and ATM -rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). Findings After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene–environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1 -rs889312 were significantly shorter than non-carriers (mean height 162·4 cm [95% CI 162·1–162·7] vs 163·1 cm [162·9–163·2]; p=0·01 after allowance for multiple testing). Interpretation Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. Funding Cancer Research UK and the UK Medical Research Council.
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subjectAbridged Index Medicus ; Adenine ; Age Factors ; Alcohol Drinking ; Articles ; Ataxia Telangiectasia Mutated Proteins ; Biological and medical sciences ; Body Height ; Body Mass Index ; Breast cancer ; Breast Feeding ; Breast Neoplasms - etiology ; Breast Neoplasms - genetics ; Caspase 8 - genetics ; Cell Cycle Proteins - genetics ; Cytosine ; Data collection ; DNA-Binding Proteins - genetics ; Environment ; Environment. Living conditions ; Female ; General aspects ; Genetic aspects ; Genetic polymorphisms ; Genotype ; Gynecology. Andrology. Obstetrics ; Health services ; Hormone Replacement Therapy ; Humans ; Internal Medicine ; Leucine Zippers - genetics ; Mammary gland diseases ; MAP Kinase Kinase Kinase 1 - genetics ; Medical research ; Medical sciences ; Menarche - physiology ; Menopause - physiology ; Microfilament Proteins - genetics ; Middle Aged ; Parity ; Phosphatidylinositol 3-Kinases - genetics ; Phosphoproteins - genetics ; Polymorphism, Genetic - genetics ; Pregnancy ; Prospective Studies ; Protein-Serine-Threonine Kinases - genetics ; Public health. Hygiene ; Public health. Hygiene-occupational medicine ; Receptor, Fibroblast Growth Factor, Type 2 - genetics ; Receptors, Progesterone - genetics ; Risk Factors ; Transforming Growth Factor beta1 - genetics ; Tumor Suppressor Proteins - genetics ; Tumors ; Variables ; Womens health ; Young Adult
ispartofLancet, 2010, Vol.375 (9732), p.2143-2151
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descriptionSummary Background Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene–environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. Methods We tested gene–environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms ( FGFR2 -rs2981582, TNRC9 -rs3803662, 2q35-rs13387042, MAP3K1 -rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8 -rs1045485, LSP1 -rs3817198, 5q-rs30099, TGFB1 -rs1982073, and ATM -rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). Findings After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene–environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1 -rs889312 were significantly shorter than non-carriers (mean height 162·4 cm [95% CI 162·1–162·7] vs 163·1 cm [162·9–163·2]; p=0·01 after allowance for multiple testing). Interpretation Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. Funding Cancer Research UK and the UK Medical Research Council.
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1Adenine
2Age Factors
3Alcohol Drinking
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5Ataxia Telangiectasia Mutated Proteins
6Biological and medical sciences
7Body Height
8Body Mass Index
9Breast cancer
10Breast Feeding
11Breast Neoplasms - etiology
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13Caspase 8 - genetics
14Cell Cycle Proteins - genetics
15Cytosine
16Data collection
17DNA-Binding Proteins - genetics
18Environment
19Environment. Living conditions
20Female
21General aspects
22Genetic aspects
23Genetic polymorphisms
24Genotype
25Gynecology. Andrology. Obstetrics
26Health services
27Hormone Replacement Therapy
28Humans
29Internal Medicine
30Leucine Zippers - genetics
31Mammary gland diseases
32MAP Kinase Kinase Kinase 1 - genetics
33Medical research
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35Menarche - physiology
36Menopause - physiology
37Microfilament Proteins - genetics
38Middle Aged
39Parity
40Phosphatidylinositol 3-Kinases - genetics
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45Protein-Serine-Threonine Kinases - genetics
46Public health. Hygiene
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48Receptor, Fibroblast Growth Factor, Type 2 - genetics
49Receptors, Progesterone - genetics
50Risk Factors
51Transforming Growth Factor beta1 - genetics
52Tumor Suppressor Proteins - genetics
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titleGene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study
authorTravis, Ruth C, Dr ; Reeves, Gillian K, PhD ; Green, Jane, MD ; Bull, Diana ; Tipper, Sarah J, MSc ; Baker, Krys ; Beral, Valerie, Prof ; Peto, Richard, Prof ; Bell, John, Prof ; Zelenika, Diana, PhD ; Lathrop, Mark, Prof
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37Microfilament Proteins - genetics
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43Pregnancy
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45Protein-Serine-Threonine Kinases - genetics
46Public health. Hygiene
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48Receptor, Fibroblast Growth Factor, Type 2 - genetics
49Receptors, Progesterone - genetics
50Risk Factors
51Transforming Growth Factor beta1 - genetics
52Tumor Suppressor Proteins - genetics
53Tumors
54Variables
55Womens health
56Young Adult
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codenLANCAO
notesCollaborators listed at end of paper
abstractSummary Background Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene–environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. Methods We tested gene–environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms ( FGFR2 -rs2981582, TNRC9 -rs3803662, 2q35-rs13387042, MAP3K1 -rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8 -rs1045485, LSP1 -rs3817198, 5q-rs30099, TGFB1 -rs1982073, and ATM -rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). Findings After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene–environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1 -rs889312 were significantly shorter than non-carriers (mean height 162·4 cm [95% CI 162·1–162·7] vs 163·1 cm [162·9–163·2]; p=0·01 after allowance for multiple testing). Interpretation Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. Funding Cancer Research UK and the UK Medical Research Council.
copKidlington
pubElsevier Ltd
pmid20605201
doi10.1016/S0140-6736(10)60636-8
oafree_for_read