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ABSTRACT Schernhammer ES, Hunter DJ, Pollak M, Hankinson SE. A growth hormone polymorphism at position 1663 in intron 4 of the GH1 gene is not associated with breast cancer risk. Int J Cancer Prev 2004;1(1):33-37 A previous report found a polymorphism at position 1663 (T1663A) in intron 4 of the growth hormone (GH1) to be significantly related to colorectal cancer. Growth hormone (GH) is a primary determinant of insulin-like growth factor (IGF) levels and IGF-I appears to be associated with breast cancer risk, particularly among premenopausal women. We utilized a nested case-control design within the large, prospective Nurses’ Health Study (NHS) cohort to investigate an association between this polymorphism in the GH1 gene and breast cancer, to our knowledge the first time in the literature. We identified 944 women with incident breast cancer and 1,272 matched controls from the NHS and genotyped them at position 1663 in intron 4 of the GH1 gene. For most of these women we had previously measured IGF-I and IGFBP-3 plasma levels. Age-adjusted mean circulating IGF-I levels were 165.2 ± 4 ng/ml in the individuals with the AA genotype and did not vary by genotype (AT = 166.9 ± 2 ng/ml; TT = 160.5 ± 3 ng/ml [p >0.5 for all pairwise comparisons]) and the GH1 genotype was not associated with circulating IGFBP-3 level. There was no statistically significant relationship between genotype and RR for breast cancer, overall. However, among the small group of premenopausal women we observed a non-significant, positive relationship between genotype AA and breast cancer risk (multivariate RR 2.30, 95% CI, 0.94-5.66). Our data do not demonstrate a significant influence of this locus on breast cancer risk, but we cannot exclude a minor influence, or an influence confined to subgroups.
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