TY - JOUR

T1 - Common breast cancer risk alleles and risk assessment

T2 - A study on 35,441 individuals from the Danish general population

AU - Näslund-Koch, C

AU - Nordestgaard, B G

AU - Bojesen, S E

N1 - © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2017

Y1 - 2017

N2 - BACKGROUND: We hypothesized that common breast cancer risk alleles are associated with incidences of breast cancer and other cancers in the general population, and identify low risk women among those invited for screening mammography.PARTICIPANTS AND METHODS: 35,441 individuals from the Danish general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0-2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer.RESULTS: Breast cancer incidence in the 19,010 women was increased across allele sum quintiles (log-rank trend test; p=1*10(-12)), but not incidence of other cancers (p=0.41). Age- and study-adjusted hazard ratio for the 5(th) vs. 1(st) allele sum quintile was 1.82(95% confidence interval;1.53-2.18). Corresponding hazard ratios per allele were 1.04(1.03-1.05) and 1.05(1.02-1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year old women, the starting age for screening mammography in Denmark, the average 5-year breast cancer risk was 1.5%, overall and 1.1%, 1.4%, 1.6%, 1.7%, 2.1%, for the 1(st) through 5(th) quintile, respectively. Based on age, nulliparity, familial history, and allele sum, 25% of women aged 50-69, and 94% of women aged 40-49, had absolute 5-year breast cancer risks ≤ 1.5%. Using polygenic risk score led to similar results.CONCLUSION: Common breast cancer risk alleles are associated with incidence and mortality of breast cancer in the general population, but not with other cancers. After including breast cancer allele sum in risk assessment, 25% of women currently being offered screening mammography had an absolute 5-year risk below the cutoff of average risk for a 50 year old woman.

AB - BACKGROUND: We hypothesized that common breast cancer risk alleles are associated with incidences of breast cancer and other cancers in the general population, and identify low risk women among those invited for screening mammography.PARTICIPANTS AND METHODS: 35,441 individuals from the Danish general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0-2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer.RESULTS: Breast cancer incidence in the 19,010 women was increased across allele sum quintiles (log-rank trend test; p=1*10(-12)), but not incidence of other cancers (p=0.41). Age- and study-adjusted hazard ratio for the 5(th) vs. 1(st) allele sum quintile was 1.82(95% confidence interval;1.53-2.18). Corresponding hazard ratios per allele were 1.04(1.03-1.05) and 1.05(1.02-1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year old women, the starting age for screening mammography in Denmark, the average 5-year breast cancer risk was 1.5%, overall and 1.1%, 1.4%, 1.6%, 1.7%, 2.1%, for the 1(st) through 5(th) quintile, respectively. Based on age, nulliparity, familial history, and allele sum, 25% of women aged 50-69, and 94% of women aged 40-49, had absolute 5-year breast cancer risks ≤ 1.5%. Using polygenic risk score led to similar results.CONCLUSION: Common breast cancer risk alleles are associated with incidence and mortality of breast cancer in the general population, but not with other cancers. After including breast cancer allele sum in risk assessment, 25% of women currently being offered screening mammography had an absolute 5-year risk below the cutoff of average risk for a 50 year old woman.

U2 - 10.1093/annonc/mdw536

DO - 10.1093/annonc/mdw536

M3 - Journal article

C2 - 28177461

VL - 28

SP - 175

EP - 181

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 1

ER -