Environment and Breast Cancer: Science Review

Evidence From Humans
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Possible association of beta2- and beta3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer
Huang, X. E., Hamajima, N., Saito, T., Matsuo, K., Mizutani, M., Iwata, H., Iwase, T., Miura, S., Mizuno, T., Tokudome, S., Tajima, K. Breast Cancer Research. 2001. 3:4, 264-9.
Topic area
Body size - Genetic variability
Study design
Hospital based case-control study
Funding agency
Other: Ministry of Education, Science, Sports, and
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Pre menopausal
Post menopausal
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Hstopathologically confirmed prevalent cases, diagnosed less than 5 years prior to study. Controls were noncancer outpatients at same hospital for annual health check up during same period.
Exposures investigated
BMI, ADRB2 and ADRB3 allele frequencies, used PCR-RFLP
How exposure was measured
Biological questionnaire, self-administered
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Yes: Models adjusted for age only
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Description of major analysis
Logistic regression analysis of ADRB2 and ADRB3 genotypes and breast cancer, including effect modification by BMI
Strength of associations reported
Those with mutant Glu allele in ADRB2 showed nonsignificant reduction in risk, age adjusted OR=0.65 (CI: 0.37-1.16); No difference by BMI
Those with mutant Arg allele in ADRB3 showed adjusted OR=0.83 (CI: 0.54-1.29); No difference by BMI
Various combinations of Glu and Arg did not show significant associations with risk
BACKGROUND: The involvement of beta2-adrenergic receptor (ADRB2) and beta3-adrenergic receptor (ADRB3) in both adipocyte lipolysis and thermogenic activity suggests that polymorphisms in the encoding genes might be linked with interindividual variation in obesity, an important risk factor for postmenopausal breast cancer. In order to examine the hypothesis that genetic variations in ADRB2 and ADRB3 represent interindividual susceptibility factors for obesity and breast cancer, we conducted a hospital-based, case-control study in the Aichi Cancer Center, Japan. METHODS: A self-administered questionnaire was given to 200 breast cancer patients and 182 control individuals, and pertinent information on lifestyle, family history and reproduction was collected. ADRB2 and ADRB3 genotypes were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism assessment. RESULTS: Twenty-five (12.4%) breast cancer patients and 32 (17.6%) control individuals were found to bear a glutamic acid (Glu) allele for the ADRB2 gene (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.38-1.18), and 60 (30.0%) breast cancer patients and 61 (33.5%) control individuals were found to bear an Arg allele for the ADRB3 gene (OR 0.85, 95% CI 0.55-1.31). A significantly lower risk was observed in those who carried the Glu ADRB2 allele and who reported first childbirth when they were younger than 25 years (OR 0.35; 95% CI 0.13-0.99). CONCLUSION: A potential association may exist between risk of breast cancer and polymorphisms in the ADRB2 and ADRB3 genes; further studies in larger samples and/or in different ethnic groups are warranted to investigate this potential association.