17 research outputs found
Comparison of the proteome of Mycobacterium tuberculosis strain H37Rv with clinical isolate CDC 1551
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
Objective. Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods. Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results. We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 034, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions. rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers. (C) 2015 Elsevier Inc. All rights reserved.Peer reviewe
Distinct Clinicopathological and Prognostic Features of Thin Nodular Primary Melanomas: An International Study from 17 Centers
Background: Nodular melanoma (NM) is more likely to be fatal compared
with other melanoma subtypes, an effect attributed to its greater
Breslow thickness.
Methods: Clinicopathological features of NM and superficial spreading
melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), the United
States, and Australia between 2006 and 2015, were analyzed by
multivariable logistic regression analysis, with emphasis on thin (T1 <=
1.0mm) melanomas. Cox analysis assessed melanoma-specific survival. All
statistical tests were two sided.
Results: In all, 20 132 melanomas (NM: 5062, SSM: 15 070) were included.
Compared with T1 SSM, T1 NM was less likely to have regression (odds
ratio [OR] = 0.46, 95% confidence interval [CI] = 0.29 to 0.72) or
nevus remnants histologically (OR = 0.60, 95% CI = 0.42 to 0.85), and
more likely to have mitoses (OR = 1.97, 95% CI = 1.33 to 2.93) and
regional metastasis (OR = 1.77, 95% CI = 1.02 to 3.05). T1 NM had a
higher mitotic rate than T1 SSM (adjusted geometric mean = 2.2, 95% CI
= 1.9 to 2.5 vs 1.6, 95% CI = 1.5 to 1.7 per mm(2), P < .001). Cox
multivariable analysis showed a higher risk for melanoma-specific death
for NM compared with SSM for T1 (HR = 2.10, 95% CI = 1.24 to 3.56) and
T2 melanomas (HR = 1.30, 95% CI = 1.01 to 1.68), and after accounting
for center heterogeneity, the difference was statistically significant
only for T1 (HR = 2.20, 95% CI = 1.28 to 3.78). The NM subtype did not
confer increased risk within each stratum (among localized tumors or
cases with regional metastasis).
Conclusions: T1 NM (compared with T1 SSM) was associated with a
constellation of aggressive characteristics that may confer a worse
prognosis. Our results indicate NM is a high-risk melanoma subtype that
should be considered for inclusion in future prognostic classifications
of melanoma