Evidence From Humans
 
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HSD17B1 gene polymorphisms and risk of endometrial and breast cancer
Setiawan, V. W., Hankinson, S. E., Colditz, G. A., Hunter, D. J., De Vivo, I. Cancer Epidemiology, Biomarkers and Prevention. 2004. 13:2, 213-9.
Topic area
Body size - Genetic variability
Study design
Nested case-control
Funding agency
NIH, ACS, NCI
Study Participants
Number of Cases
1007 (invasive only)
Menopausal Status
The menopausal status of women included in this study is listed here.
Pre menopausal
Post menopausal
Number of Controls
Control: 1441
Cohort participation rate
Greater than 70%
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
In: women diagnosed with invasive breast cancer anytime after blood collection (1989-1990) and before 6/1/98; women in the Nurses' Health Study (NHS); between the ages of 30 and 55 in 1976 when the NHS began; gave a blood sample between 1989 and 1990. Incident cases confirmed by chart-review for pathology confirmation. Cohort controls matched on year of birth, menopausal status, postmenopausal hormone use, time/month/fasting at blood draw. Ex: previously diagnosed with cancer (not including nonmelanoma skin cancer)
Exposure Investigated
Exposures investigated
BMI, HSD17B1 allele frequencies, used PCR-RFLP
How exposure was measured
Biological Questionnaire, self-administered (does not explain how anthropometric data was obtained)
Exposure assessment comment
Does not explain how BMI was obtained
Statistical Analysis
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
No
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.
Adequately controlled, Confounders: BMI, age, time and date of blood draw, fasting status at blood draw and laboratory batch
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Yes
Description of major analysis
Logistic regression analysis of HSD17B1 genotype and breast cancer, including effect modification by BMI and by HSD17B1 (hormones) genotypes
Strength of associations reported
No association between any HSD17B1 genotypes and BC risk, even following stratification by menopausal status
In postmenopausal women, significant interactions were found; Among women with BMI >30, +1954A/G type AA showed OR=1.77 (0.99-3.17) when compared to AG or GG type; Among women with BMI<25, those with the CA or AA genotype of +1322C/A yielded an OR=0.74 (CI: 0.57-0.97) compared to the CC genotype
Results Comments
AA genotype may be important to consider in relation to serum estradiol levels in premenopausal lean women, who have limited number of other sources of estrogens (no HRT or peripheral conversion of androgens in adipose); Yet these altered estrogen levels did not translate into increased BC risk
Reviewers Comments
Strengths: one of the first population-based studies to evaluate the HSD17B1 polymorphisms +1954/G (Ser312Gly) in relation to breast cancer; first pop-based study to evaluate the polymorphisms HSD17B1 gene (+1004C/T and +1322C/A) in breast cancer risk and how they relate to plasma steroid hormone levels; first study to infer haplotypes in the HSD17B1 gene and compare their frequency distributions in cancer cases and controls; validated the single nucleotide polymorphisms in a subset of the population and confirmed the findings with another study Limitations: does not provide ORs or CIs for breast cancer risk by HSD genotypes and BMI;
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