Reproductive factors as risk modifiers of breast cancer in BRCA mutation carriers and high-risk non-carriers

KOHBRA Study Group

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

This study was conducted to identify the role of reproductive factors as environmental modifiers for breast cancer (BC) risk in clinic-based, East-Asian BRCA1 and BRCA2 mutation carriers and non-carriers with high-risk criteria of BRCA mutations (family history (FH) of BC, early-onset BC (aged =40 years)). A total of 581 women who were BRCA carriers (222 BRCA1 and 359 BRCA2), 1,083 non-carriers with FH, and 886 non-carriers with early-onset BC were enrolled and interviewed to examine the reproductive factors, from 2007 to 2014. The hazard ratio (HR) and its 95% confidence interval (CI) in the weighted Cox regression model were used to calculate the BC risk based on the reproductive factors. Earlier menarche increased BC risk by 3.49-fold in BRCA2 mutation carriers (95%CI=2.03-6.00) and 3.30-fold in non-carriers with FH (95%CI=1.73-6.34), but was insignificantly associated with BRCA1 carriers and non-carriers for early-onset BC (P-heterogeneity=0.047). Higher parity decreased BC risk in BRCA carriers and non-carriers with FH, especially in BRCA1 carriers (HR=0.27, 95% CI=0.09-0.83 for two parity; and HR=0.23, 95%CI=0.05-1.00 for ≥3 parity), but increased the early-onset BC risk (HR=4.63, 95%CI=2.56-8.51 for > 3 parity, p-heterogeneity=0.045). Oral contraceptive (OC) use and longer estrogen exposure periods (≥30 years) were associated with an increased risk of early-onset BC (HR=3.99, 95%CI=1.65-9.67; HR=7.69, 95%CI=1.96-25.01), while OC use was not associated with BC risk in other groups and longer estrogen exposure had rather decreased risk for BC risk (both p-heterogeneity < 0.001). Several reproductive factors as risk modifiers could heterogeneously be associated with BC among BRCA1/2 mutation carriers, noncarriers with FH, and early-onset BC non-carriers.

Original languageEnglish
Pages (from-to)102110-102118
Number of pages9
JournalOncotarget
Volume8
Issue number60
DOIs
Publication statusPublished - 2017 Jan 1

Fingerprint

Breast Neoplasms
Mutation
Confidence Intervals
Parity
Oral Contraceptives
Estrogens
Menarche
Proportional Hazards Models
Odds Ratio

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

@article{c67d2f464b6545dcbea67eb7f57984b0,
title = "Reproductive factors as risk modifiers of breast cancer in BRCA mutation carriers and high-risk non-carriers",
abstract = "This study was conducted to identify the role of reproductive factors as environmental modifiers for breast cancer (BC) risk in clinic-based, East-Asian BRCA1 and BRCA2 mutation carriers and non-carriers with high-risk criteria of BRCA mutations (family history (FH) of BC, early-onset BC (aged =40 years)). A total of 581 women who were BRCA carriers (222 BRCA1 and 359 BRCA2), 1,083 non-carriers with FH, and 886 non-carriers with early-onset BC were enrolled and interviewed to examine the reproductive factors, from 2007 to 2014. The hazard ratio (HR) and its 95{\%} confidence interval (CI) in the weighted Cox regression model were used to calculate the BC risk based on the reproductive factors. Earlier menarche increased BC risk by 3.49-fold in BRCA2 mutation carriers (95{\%}CI=2.03-6.00) and 3.30-fold in non-carriers with FH (95{\%}CI=1.73-6.34), but was insignificantly associated with BRCA1 carriers and non-carriers for early-onset BC (P-heterogeneity=0.047). Higher parity decreased BC risk in BRCA carriers and non-carriers with FH, especially in BRCA1 carriers (HR=0.27, 95{\%} CI=0.09-0.83 for two parity; and HR=0.23, 95{\%}CI=0.05-1.00 for ≥3 parity), but increased the early-onset BC risk (HR=4.63, 95{\%}CI=2.56-8.51 for > 3 parity, p-heterogeneity=0.045). Oral contraceptive (OC) use and longer estrogen exposure periods (≥30 years) were associated with an increased risk of early-onset BC (HR=3.99, 95{\%}CI=1.65-9.67; HR=7.69, 95{\%}CI=1.96-25.01), while OC use was not associated with BC risk in other groups and longer estrogen exposure had rather decreased risk for BC risk (both p-heterogeneity < 0.001). Several reproductive factors as risk modifiers could heterogeneously be associated with BC among BRCA1/2 mutation carriers, noncarriers with FH, and early-onset BC non-carriers.",
author = "{KOHBRA Study Group} and Boyoung Park and Hopper, {John L.} and Win, {Aung K.} and Dowty, {James G.} and Sung, {Ho Kyung} and Choonghyun Ahn and Kim, {Sung Won} and Lee, {Min Hyuk} and Jihyoun Lee and Lee, {Jong Won} and Eunyoung Kang and Yu, {Jong Han} and Kim, {Ku Sang} and Moon, {Byung In} and Wonshik Han and Noh, {Dong Young} and Park, {Sue K.} and Kwak, {Beom Seok} and Byeongwoo Park and Son, {Byung Ho} and Yom, {Cha Kyong} and Park, {Chan Heun} and Yoon, {Chan Seok} and Lee, {Chang Hyun} and Yoon, {Dae Sung} and Choi, {Doo Ho} and Eundeok Chang and Kim, {Eun Kyu} and Lee, {Hae Kyung} and Park, {Hai Lin} and Hyde Lee and Moon, {Hyeong Gon} and Kim, {Hyun Ah} and Lee, {Il Kyun} and Lee, {Jeong Eon} and Jeong Joon and Yoon, {Jung Han} and Yang, {Jung Hyun} and Keumhee Kwak and Hwang, {Ki Tae} and Kim, {Lee Su} and Hur, {Min Hee} and Park, {Min Ho} and Chang, {Myung Chul} and Paik, {Nam Sun} and Han, {Sang Ah} and Jung, {Sang Seol} and Woo, {Sang Uk} and Oh, {Se Jeong} and Sehwan Han",
year = "2017",
month = "1",
day = "1",
doi = "10.18632/oncotarget.22193",
language = "English",
volume = "8",
pages = "102110--102118",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "60",

}

Reproductive factors as risk modifiers of breast cancer in BRCA mutation carriers and high-risk non-carriers. / KOHBRA Study Group.

In: Oncotarget, Vol. 8, No. 60, 01.01.2017, p. 102110-102118.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Reproductive factors as risk modifiers of breast cancer in BRCA mutation carriers and high-risk non-carriers

AU - KOHBRA Study Group

AU - Park, Boyoung

AU - Hopper, John L.

AU - Win, Aung K.

AU - Dowty, James G.

AU - Sung, Ho Kyung

AU - Ahn, Choonghyun

AU - Kim, Sung Won

AU - Lee, Min Hyuk

AU - Lee, Jihyoun

AU - Lee, Jong Won

AU - Kang, Eunyoung

AU - Yu, Jong Han

AU - Kim, Ku Sang

AU - Moon, Byung In

AU - Han, Wonshik

AU - Noh, Dong Young

AU - Park, Sue K.

AU - Kwak, Beom Seok

AU - Park, Byeongwoo

AU - Son, Byung Ho

AU - Yom, Cha Kyong

AU - Park, Chan Heun

AU - Yoon, Chan Seok

AU - Lee, Chang Hyun

AU - Yoon, Dae Sung

AU - Choi, Doo Ho

AU - Chang, Eundeok

AU - Kim, Eun Kyu

AU - Lee, Hae Kyung

AU - Park, Hai Lin

AU - Lee, Hyde

AU - Moon, Hyeong Gon

AU - Kim, Hyun Ah

AU - Lee, Il Kyun

AU - Lee, Jeong Eon

AU - Joon, Jeong

AU - Yoon, Jung Han

AU - Yang, Jung Hyun

AU - Kwak, Keumhee

AU - Hwang, Ki Tae

AU - Kim, Lee Su

AU - Hur, Min Hee

AU - Park, Min Ho

AU - Chang, Myung Chul

AU - Paik, Nam Sun

AU - Han, Sang Ah

AU - Jung, Sang Seol

AU - Woo, Sang Uk

AU - Oh, Se Jeong

AU - Han, Sehwan

PY - 2017/1/1

Y1 - 2017/1/1

N2 - This study was conducted to identify the role of reproductive factors as environmental modifiers for breast cancer (BC) risk in clinic-based, East-Asian BRCA1 and BRCA2 mutation carriers and non-carriers with high-risk criteria of BRCA mutations (family history (FH) of BC, early-onset BC (aged =40 years)). A total of 581 women who were BRCA carriers (222 BRCA1 and 359 BRCA2), 1,083 non-carriers with FH, and 886 non-carriers with early-onset BC were enrolled and interviewed to examine the reproductive factors, from 2007 to 2014. The hazard ratio (HR) and its 95% confidence interval (CI) in the weighted Cox regression model were used to calculate the BC risk based on the reproductive factors. Earlier menarche increased BC risk by 3.49-fold in BRCA2 mutation carriers (95%CI=2.03-6.00) and 3.30-fold in non-carriers with FH (95%CI=1.73-6.34), but was insignificantly associated with BRCA1 carriers and non-carriers for early-onset BC (P-heterogeneity=0.047). Higher parity decreased BC risk in BRCA carriers and non-carriers with FH, especially in BRCA1 carriers (HR=0.27, 95% CI=0.09-0.83 for two parity; and HR=0.23, 95%CI=0.05-1.00 for ≥3 parity), but increased the early-onset BC risk (HR=4.63, 95%CI=2.56-8.51 for > 3 parity, p-heterogeneity=0.045). Oral contraceptive (OC) use and longer estrogen exposure periods (≥30 years) were associated with an increased risk of early-onset BC (HR=3.99, 95%CI=1.65-9.67; HR=7.69, 95%CI=1.96-25.01), while OC use was not associated with BC risk in other groups and longer estrogen exposure had rather decreased risk for BC risk (both p-heterogeneity < 0.001). Several reproductive factors as risk modifiers could heterogeneously be associated with BC among BRCA1/2 mutation carriers, noncarriers with FH, and early-onset BC non-carriers.

AB - This study was conducted to identify the role of reproductive factors as environmental modifiers for breast cancer (BC) risk in clinic-based, East-Asian BRCA1 and BRCA2 mutation carriers and non-carriers with high-risk criteria of BRCA mutations (family history (FH) of BC, early-onset BC (aged =40 years)). A total of 581 women who were BRCA carriers (222 BRCA1 and 359 BRCA2), 1,083 non-carriers with FH, and 886 non-carriers with early-onset BC were enrolled and interviewed to examine the reproductive factors, from 2007 to 2014. The hazard ratio (HR) and its 95% confidence interval (CI) in the weighted Cox regression model were used to calculate the BC risk based on the reproductive factors. Earlier menarche increased BC risk by 3.49-fold in BRCA2 mutation carriers (95%CI=2.03-6.00) and 3.30-fold in non-carriers with FH (95%CI=1.73-6.34), but was insignificantly associated with BRCA1 carriers and non-carriers for early-onset BC (P-heterogeneity=0.047). Higher parity decreased BC risk in BRCA carriers and non-carriers with FH, especially in BRCA1 carriers (HR=0.27, 95% CI=0.09-0.83 for two parity; and HR=0.23, 95%CI=0.05-1.00 for ≥3 parity), but increased the early-onset BC risk (HR=4.63, 95%CI=2.56-8.51 for > 3 parity, p-heterogeneity=0.045). Oral contraceptive (OC) use and longer estrogen exposure periods (≥30 years) were associated with an increased risk of early-onset BC (HR=3.99, 95%CI=1.65-9.67; HR=7.69, 95%CI=1.96-25.01), while OC use was not associated with BC risk in other groups and longer estrogen exposure had rather decreased risk for BC risk (both p-heterogeneity < 0.001). Several reproductive factors as risk modifiers could heterogeneously be associated with BC among BRCA1/2 mutation carriers, noncarriers with FH, and early-onset BC non-carriers.

UR - http://www.scopus.com/inward/record.url?scp=85034852534&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034852534&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.22193

DO - 10.18632/oncotarget.22193

M3 - Article

AN - SCOPUS:85034852534

VL - 8

SP - 102110

EP - 102118

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 60

ER -