Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases.
BACKGROUND
Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.


METHODS
We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.


RESULTS
Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.


CONCLUSIONS
Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.
Huijts
Petra E A
PE
Department of Clinical Genetics, K5-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. p.huijts@lumc.nl
Vreeswijk
Maaike P G
MP
Kroeze-Jansema
Karin H G
KH
Jacobi
Catharina E
CE
Seynaeve
Caroline
C
Krol-Warmerdam
Elly M M
EM
Wijers-Koster
Pauline M
PM
Blom
Jannet C
JC
Pooley
Karen A
KA
Klijn
Jan G M
JG
Tollenaar
Rob A E M
RA
Devilee
Peter
P
van Asperen
Christi J
CJ
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006609:High Mobility Group Proteins; D006801:Humans; D015994:Incidence; D008207:Lymphatic Metastasis; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D015534:Trans-Activators
D051017:Apoptosis Regulatory Proteins; D006609:High Mobility Group Proteins; C489183:LSP1 protein, human; D008840:Microfilament Proteins; D011980:Receptors, Progesterone; C521752:TOX3 protein, human; D015534:Trans-Activators; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human