Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.
BACKGROUND
Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs) and height, body mass index (BMI) and hormone replacement therapy (HRT).


METHODS
We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case-control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model.


RESULTS
One SNP (rs851987 in ESR1) tended to interact with height, with an increasingly protective effect of the major allele in taller women (p = 0.007) and rs13281615 (on 8q24) tended to confer risk only in non users of HRT (p-for interaction = 0.03). There were no significant interactions after correction for multiple testing.


CONCLUSIONS
We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.
Department of Clinical Chemistry, Lund University, Malmö, Sweden.
Sophia
S
Harlid
Salma
S
Butt
Malin I L
MI
Ivarsson
Jorunn Erla
JE
Eyfjörd
Per
P
Lenner
Jonas
J
Manjer
Joakim
J
Dillner
Joyce
J
Carlson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001827:Body Height; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D007055:Iceland; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013548:Sweden
D005819:Genetic Markers