Estrogen receptor polymorphism at codon 325 and risk of breast cancer in women before age forty.

BACKGROUND: The estrogen receptor (ER) protein is believed to play a role in the development and progression of breast cancer. In a previously published U.S. clinic-based study, a polymorphism in the ER gene (codon 325, CCC --> CCG) was found to be more common in 34 case subjects with a family history of breast cancer than in 154 case subjects without such a history (mean allele frequencies +/- standard error = 0.28+/-0.05 versus 0.11+/-0.02; P<.001). To determine whether this polymorphism is a risk factor for early-onset breast cancer, we conducted a population-based, case-control-family study in Australia. METHODS: Case subjects under the age of 40 years with a first primary breast cancer and control subjects, frequency-matched to the case subjects on the basis of age, and their relatives were interviewed to assess the family history of breast cancer. Polymorphism status of the ER gene was determined for 388 case subjects and 294 control subjects. All statistical tests were two-tailed. RESULTS: There was no association between ER gene polymorphism status and breast cancer, before or after adjustment for risk factors. There was no difference in allele frequencies between case subjects and control subjects (0.232+/-0.015 versus 0.209+/-0.017; P = .4) or between women with and without a family history of breast cancer (P = .3), irrespective of case-control status. The findings were not altered when different definitions of family history of breast cancer were used and when allele frequencies were adjusted for residence and country of birth. CONCLUSION: We found no evidence that the ER codon 325 polymorphism is associated with breast cancer before the age of 40 years or with a family history of breast cancer, despite ample power to detect effects half the magnitude of those previously reported.

Androgen receptor exon 1 CAG repeat length and breast cancer in women before age forty years.

BACKGROUND: We conducted a population-based, case-control-family study to determine whether androgen receptor (AR) exon 1 polymorphic CAG repeat length (CAGn) was a risk factor for early-onset breast cancer in the Australian population. METHODS: Case subjects under 40 years of age at diagnosis of a first primary breast cancer and age-matched control subjects were interviewed to assess family history and other risk factors. AR CAGn length was determined for 368 case subjects and 284 control subjects. Distributions in the two groups were compared by linear and logistic regression, allowing adjustment for measured risk factors. All statistical tests were two-tailed. RESULTS: When analyzed as either a continuous or a dichotomous variable, there was no association between CAG, length and breast cancer risk, before or after adjustment for risk factors. Mean (95% confidence interval [CI]) CAGn lengths were 22.0 (21.8-22.2) for case subjects and 22.0 (21.7-22.3) for control subjects (P = .9). The frequency (95% CI) of alleles with 22 or more CAGn repeats was 0.531 (0.494-0.568) for case subjects and 0.507 (0.465-0.549) for control subjects (P = .4). After adjustment, the average effect on log OR (odds ratio) per allele was 0.16 (95% CI = -0.03 to 0.40; P = .2), and the effect of any allele was equivalent to an OR of 1.40 (95% CI = 0.94-2.09; P = .1). Stratification by family history also failed to reveal any association. Similar results were obtained when alleles were defined by other cutoff points. CONCLUSION: We found no evidence for an association between AR exon 1 CAGn length and breast cancer risk in women under the age of 40, despite having 80% power to detect modest effects.