DNA repair gene variants associated with benign breast disease in high cancer risk women

Timothy J. Jorgensen, Kathy J. Helzlsouer, Sandra C. Clipp, Judy Hoffman Bolton, Rosa M Crum, Kala Visvanathan

Research output: Contribution to journalArticle

Abstract

Benign breast disease (BBD) is a risk factor for breast cancer and may have a heritable component. Deficient DNA repair has been implicated in breast cancer etiology and may exert its effect before BBD, a known precursor. The association between allelic variants in DNA repair genes and BBD was examined in a cohort of women in Washington County, Maryland. BBD was defined by two criteria: (a) a physician diagnosis of BBD or fibrocystic disease and/or (b) a benign breast biopsy. 3,212 women without BBD at baseline were genotyped for 12 candidate single nucleotide polymorphisms in seven DNA repair genes. Of these women, 482 subsequently reported a diagnosis of BBD. The Cox model was used to calculate hazard ratios (HR). Variant alleles of XRCC1 Arg194Trp (rs1799782) and ERCC4 Arg415Gln (rs1800067) were significantly associated with BBD [HR, 1.36; 95% confidence interval (95% CI), 1.06-1.74 and HR, 1.39; 95% CI, 1.09-1.76, respectively]. Similar estimates were also observed for each of the BBD criterion used. The BBD association for ERCC4 was even stronger among women with a family history of breast cancer (HR, 2.68; 95% CI, 1.52-4.66; Pinteraction = 0.02). This study suggests that variant alleles in DNA repair genes may modify BBD risk, a potential intermediate marker of breast cancer risk, particularly among high-risk subgroups.

Original languageEnglish (US)
Pages (from-to)346-350
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Breast Diseases
DNA Repair
Genes
Neoplasms
Breast Neoplasms
Confidence Intervals
Alleles
DNA Repair-Deficiency Disorders
Fibrocystic Breast Disease
Proportional Hazards Models
Single Nucleotide Polymorphism
Breast
Physicians
Biopsy

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

DNA repair gene variants associated with benign breast disease in high cancer risk women. / Jorgensen, Timothy J.; Helzlsouer, Kathy J.; Clipp, Sandra C.; Bolton, Judy Hoffman; Crum, Rosa M; Visvanathan, Kala.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 18, No. 1, 01.2009, p. 346-350.

Research output: Contribution to journalArticle

Jorgensen, Timothy J. ; Helzlsouer, Kathy J. ; Clipp, Sandra C. ; Bolton, Judy Hoffman ; Crum, Rosa M ; Visvanathan, Kala. / DNA repair gene variants associated with benign breast disease in high cancer risk women. In: Cancer Epidemiology Biomarkers and Prevention. 2009 ; Vol. 18, No. 1. pp. 346-350.
@article{5b3911752cc447129107df6de97e98dd,
title = "DNA repair gene variants associated with benign breast disease in high cancer risk women",
abstract = "Benign breast disease (BBD) is a risk factor for breast cancer and may have a heritable component. Deficient DNA repair has been implicated in breast cancer etiology and may exert its effect before BBD, a known precursor. The association between allelic variants in DNA repair genes and BBD was examined in a cohort of women in Washington County, Maryland. BBD was defined by two criteria: (a) a physician diagnosis of BBD or fibrocystic disease and/or (b) a benign breast biopsy. 3,212 women without BBD at baseline were genotyped for 12 candidate single nucleotide polymorphisms in seven DNA repair genes. Of these women, 482 subsequently reported a diagnosis of BBD. The Cox model was used to calculate hazard ratios (HR). Variant alleles of XRCC1 Arg194Trp (rs1799782) and ERCC4 Arg415Gln (rs1800067) were significantly associated with BBD [HR, 1.36; 95{\%} confidence interval (95{\%} CI), 1.06-1.74 and HR, 1.39; 95{\%} CI, 1.09-1.76, respectively]. Similar estimates were also observed for each of the BBD criterion used. The BBD association for ERCC4 was even stronger among women with a family history of breast cancer (HR, 2.68; 95{\%} CI, 1.52-4.66; Pinteraction = 0.02). This study suggests that variant alleles in DNA repair genes may modify BBD risk, a potential intermediate marker of breast cancer risk, particularly among high-risk subgroups.",
author = "Jorgensen, {Timothy J.} and Helzlsouer, {Kathy J.} and Clipp, {Sandra C.} and Bolton, {Judy Hoffman} and Crum, {Rosa M} and Kala Visvanathan",
year = "2009",
month = "1",
doi = "10.1158/1055-9965.EPI-08-0659",
language = "English (US)",
volume = "18",
pages = "346--350",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "1",

}

TY - JOUR

T1 - DNA repair gene variants associated with benign breast disease in high cancer risk women

AU - Jorgensen, Timothy J.

AU - Helzlsouer, Kathy J.

AU - Clipp, Sandra C.

AU - Bolton, Judy Hoffman

AU - Crum, Rosa M

AU - Visvanathan, Kala

PY - 2009/1

Y1 - 2009/1

N2 - Benign breast disease (BBD) is a risk factor for breast cancer and may have a heritable component. Deficient DNA repair has been implicated in breast cancer etiology and may exert its effect before BBD, a known precursor. The association between allelic variants in DNA repair genes and BBD was examined in a cohort of women in Washington County, Maryland. BBD was defined by two criteria: (a) a physician diagnosis of BBD or fibrocystic disease and/or (b) a benign breast biopsy. 3,212 women without BBD at baseline were genotyped for 12 candidate single nucleotide polymorphisms in seven DNA repair genes. Of these women, 482 subsequently reported a diagnosis of BBD. The Cox model was used to calculate hazard ratios (HR). Variant alleles of XRCC1 Arg194Trp (rs1799782) and ERCC4 Arg415Gln (rs1800067) were significantly associated with BBD [HR, 1.36; 95% confidence interval (95% CI), 1.06-1.74 and HR, 1.39; 95% CI, 1.09-1.76, respectively]. Similar estimates were also observed for each of the BBD criterion used. The BBD association for ERCC4 was even stronger among women with a family history of breast cancer (HR, 2.68; 95% CI, 1.52-4.66; Pinteraction = 0.02). This study suggests that variant alleles in DNA repair genes may modify BBD risk, a potential intermediate marker of breast cancer risk, particularly among high-risk subgroups.

AB - Benign breast disease (BBD) is a risk factor for breast cancer and may have a heritable component. Deficient DNA repair has been implicated in breast cancer etiology and may exert its effect before BBD, a known precursor. The association between allelic variants in DNA repair genes and BBD was examined in a cohort of women in Washington County, Maryland. BBD was defined by two criteria: (a) a physician diagnosis of BBD or fibrocystic disease and/or (b) a benign breast biopsy. 3,212 women without BBD at baseline were genotyped for 12 candidate single nucleotide polymorphisms in seven DNA repair genes. Of these women, 482 subsequently reported a diagnosis of BBD. The Cox model was used to calculate hazard ratios (HR). Variant alleles of XRCC1 Arg194Trp (rs1799782) and ERCC4 Arg415Gln (rs1800067) were significantly associated with BBD [HR, 1.36; 95% confidence interval (95% CI), 1.06-1.74 and HR, 1.39; 95% CI, 1.09-1.76, respectively]. Similar estimates were also observed for each of the BBD criterion used. The BBD association for ERCC4 was even stronger among women with a family history of breast cancer (HR, 2.68; 95% CI, 1.52-4.66; Pinteraction = 0.02). This study suggests that variant alleles in DNA repair genes may modify BBD risk, a potential intermediate marker of breast cancer risk, particularly among high-risk subgroups.

UR - http://www.scopus.com/inward/record.url?scp=58349100905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58349100905&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-08-0659

DO - 10.1158/1055-9965.EPI-08-0659

M3 - Article

C2 - 19124519

AN - SCOPUS:58349100905

VL - 18

SP - 346

EP - 350

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 1

ER -