Tumor-associated auto-antibodies as early detection markers for ovarian cancer? A prospective evaluation

Abstract

Immuno-proteomic screening has identified several tumor-associated auto-antibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies.

We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53, and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited. This article is protected by copyright. All rights reserved.

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Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 in relation to terminal duct lobular unit involution of the normal breast in Caucasian and African American women: the Susan G. Komen Tissue Bank

Abstract

Lesser degrees of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini/TDLU, are associated with elevated breast cancer risk. In rodent models, the insulin-like growth factor (IGF) system regulates involution of the mammary gland. We examined associations of circulating IGF measures with TDLU involution in normal breast tissues among women without precancerous lesions. Among 715 Caucasian and 283 African American (AA) women who donated normal breast tissue samples to the Komen Tissue Bank between 2009 to 2012 (75% premenopausal), serum concentrations of IGF-I and binding protein (IGFBP)-3 were quantified using enzyme-linked immunosorbent assay. Hematoxilyn & eosin-stained tissue sections were assessed for numbers of TDLUs ("TDLU count"). Zero-inflated Poisson regression models with a robust variance estimator were used to estimate relative risks (RRs) for association of IGF measures (tertiles) with TDLU count by race and menopausal status, adjusting for potential confounders. AA (vs. Caucasian) women had higher age-adjusted mean levels of serum IGF-I (137 vs. 131 ng/mL, p=0.07) and lower levels of IGFBP-3 (4165 vs. 4684 ng/mL, p<0.0001). Postmenopausal IGFBP-3 was inversely associated with TDLU count among AA (RR_T3vs.T1=0.49, 95% CI=0.28-0.84, p-trend=0.04) and Caucasian (RR_T3vs.T1=0.64, 95% CI=0.42-0.98, p-trend=0.04) women. In premenopausal women, higher IGF-I:IGFBP-3 ratios were associated with higher TDLU count in Caucasian (RR_T3vs.T1=1.33, 95% CI=1.02-1.75, p-trend=0.04), but not in AA (RR_T3vs.T1=0.65, 95% CI=0.42-1.00, p-trend=0.05), women. Our data suggest a role of the IGF system, particularly IGFBP-3, in TDLU involution of the normal breast, a breast cancer risk factor, among Caucasian and AA women. This article is protected by copyright. All rights reserved.

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Polyunsaturated fatty acids and risk of melanoma: A Mendelian randomisation analysis

Abstract

Melanoma is the deadliest form of skin cancer, mainly affecting populations of European ancestry. Some observational studies suggest that particular diets reduce melanoma risk - putatively through an increase in polyunsaturated fatty acid (PUFA) consumption. However, interpretation of these observational findings is difficult due to residual confounding or reverse causality. To date, a randomised controlled trial has not been carried out to examine the relationship between PUFAs and melanoma. Hence, we performed a Mendelian randomisation (MR) study to evaluate the link between PUFAs and melanoma.

To perform MR we used summary results from the largest risk genome-wide association study (GWAS) meta-analysis of melanoma, consisting of 12,874 cases and 23,203 controls. As instrumental variables we selected SNPs associated with PUFA levels from a GWAS meta-analysis of PUFA levels, from the CHARGE consortium. We used the inverse variance weighted method to estimate a causal odds ratio. To aid interpretation, we established a benchmark "large" predicted change in PUFAs in which, for example, an increase in docosahexaenoic acid (DPA) of 0.17 units (equal to 1 standard deviation) moves a person from the 17^th percentile to the median.

Raising PUFA levels by a large amount (increasing DPA by 0.17 units) only negligibly changed melanoma risk - Odds Ratio [OR] = 1.03 (95% Confidence Interval [CI] = 0.96 - 1.10). Other PUFAs yielded similar results as DPA. Our MR analysis suggests that the effect of PUFA levels on melanoma risk is either zero or very small. This article is protected by copyright. All rights reserved.

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EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting

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Reporting guidelines for oncology research: helping to maximise the impact of your research

from Cancer via ola Kala on Inoreader http://ift.tt/2FpGbMI
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EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting

http://ift.tt/2EN13wD

Reporting guidelines for oncology research: helping to maximise the impact of your research

http://ift.tt/2FpGbMI