Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged <or=55 years.
The histone protein family member X (H2AFX) is important in maintaining chromatin structure and genetic stability. Genetic variants in H2AFX may alter protein functions and thus cancer risk. In this case-control study, we genotyped four common single nucleotide polymorphisms (i.e., -1654A > G [rs643788], -1420G > A [rs8551], and -1187T > C [rs7759] in the H2AFX promoter region and 1057C > T [rs7350] in the 3' untranslated region (UTR)) in 467 patients with sporadic breast cancer and 488 cancer-free controls. All female subjects were non-Hispanic whites aged <or=55 years. We found that significantly increased risk of breast cancer was associated with variant genotypes in the H2AFX promoter: adjusted odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.38-2.34 for -1654AG/GG; OR = 1.40, 95% CI = 1.07-1.83 for -1420GA/AA; and OR = 1.65, 95% CI = 1.26-2.16 for -1187TC/CC. Furthermore, the number of variant alleles in the promoter haplotypes was associated with increased risks of breast cancer in a dose-response manner (OR = 6.08, 95% CI = 3.25-11.38; OR = 6.83, 95% CI = 3.83-12.18; and OR = 23.61, 95% CI = 3.95-140.99 for one, two, and three variant alleles, respectively) (P (trend) \ < 0.0001). Age at onset of breast cancer significantly decreased as the number of variant alleles increased (P (trend) = 0.024). However, these effects were not observed in the 3'UTR 1057C > T polymorphism. Therefore, we believe that H2AFX promoter polymorphisms may contribute to the etiology of sporadic breast cancer in young non-Hispanic white women. Larger association studies and related functional studies are warranted to confirm these findings.
Lu
Jiachun
J
Department of Epidemiology, Unit 1365, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Wei
Qingyi
Q
Bondy
Melissa L
ML
Brewster
Abenaa M
AM
Bevers
Therese B
TB
Yu
Tse-Kuan
TK
Buchholz
Thomas A
TA
Meric-Bernstam
Funda
F
Hunt
Kelly K
KK
Singletary
S Eva
SE
Wang
Li-E
LE
D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D004249:DNA Damage; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006657:Histones / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk; D044465:White People
C468783:H2AX protein, human; D006657:Histones