| 1. |
- Clendenen, Tess V., et al.
(author)
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Breast cancer risk prediction in women aged 35-50 years : impact of including sex hormone concentrations in the Gail model
- 2019
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In: Breast Cancer Research. - : BioMed Central. - 1465-5411 .- 1465-542X. ; 21
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Journal article (peer-reviewed)abstract
- Background: Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Mullerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50.Methods: In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers.Results: The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer.Conclusions: AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.
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| 2. |
- Fortner, Renée T., et al.
(author)
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Ovarian cancer risk factors by tumor aggressiveness : An analysis from the Ovarian Cancer Cohort Consortium
- 2019
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:1, s. 58-69
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Journal article (peer-reviewed)abstract
- Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
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| 3. |
- Shu, Xiang, et al.
(author)
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Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
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In: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
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Journal article (peer-reviewed)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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| 4. |
- Trabert, Britton, et al.
(author)
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Antibodies Against Chlamydia trachomatis and Ovarian Cancer Risk in Two Independent Populations
- 2019
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In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 111:2, s. 129-136
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Journal article (peer-reviewed)abstract
- Background: Pelvic inflammatory disease (PID) has been associated with ovarian cancer risk. To clarify the role of Chlamydia trachomatis and other infectious agents in the development of ovarian cancer, we evaluated the association of serologic markers with incident ovarian cancer using a staged approach in two independent populations.Methods: Studies included: 1) a case-control study in Poland (244 ovarian cancers/556 control subjects) and 2) a prospective nested case-control study in the PLCO Cancer Screening Trial (160 ovarian cancers/159 control subjects). Associations of serologic marker levels with ovarian cancer risk at diagnostic as well as higher thresholds, identified in Poland and independently evaluated in PLCO, were estimated using multivariable adjusted logistic regression.Results: In the Polish study, antibodies (based on laboratory cut-point) against the chlamydia plasmid-encoded Pgp3 protein (serological gold standard) were associated with increased ovarian cancer risk (adjusted odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.20 to 2.22); when a positive result was redefined at higher levels, ovarian cancer risk was increased (cut-point 2: OR = 2.00, 95% CI = 1.38 to 2.89; cut-point 3 [max OR]: OR = 2.19, 95% CI = 1.29 to 3.73). In the prospective PLCO study, Pgp3 antibodies were associated with elevated risk at the laboratory cut-point (OR = 1.43, 95% CI = 0.78 to 2.63) and more stringent cut-points (cut-point 2: OR = 2.25, 95% CI = 1.07 to 4.71); cut-point 3: OR = 2.53, 95% CI = 0.63 to 10.08). In both studies, antibodies against other infectious agents measured were not associated with risk.Conclusions: In two independent populations, antibodies against prior/current C. trachomatis (Pgp3) were associated with a doubling in ovarian cancer risk, whereas markers of other infectious agents were unrelated. These findings lend support for an association between PID and ovarian cancer.
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