Sex plays an important role in the incidence, prognosis, and mortality of cancers, but often is not considered in disease treatment.
We quantified sex differences in cancer incidence using the United ...States Cancer Statistics (USCS) public use database and sex differences in cancer survival using Surveillance, Epidemiology, and End Results (SEER) public use data from 2001 to 2016. Age-adjusted male-to-female incidence rate ratios (IRR) with 95% confidence intervals (CI) were generated by primary cancer site, race, and age groups. In addition, age-adjusted hazard ratios with 95% CI by sex within site were generated.
In general, cancer incidence and overall survival were lower in males than females, with Kaposi sarcoma (IRR: 9.751; 95% CI, 9.287-10.242;
< 0.001) having highest male-to-female incidence, and thyroid cancers (HR, 1.774; 95% CI, 1.707-1.845) having largest male-to-female survival difference. Asian or Pacific Islanders had particularly high male-to-female incidence in larynx cancers (IRR: 8.199; 95% CI, 7.203-9.363;
< 0.001), relative to other races. Among primary brain tumors, germ cell tumors had the largest male-to-female incidence (IRR: 3.03; 95% CI, 2.798-3.284,
< 0.001).
Overall, incidence and survival of cancer vary significantly by sex, with males generally having lower incidence and survival compared with females. Male-to-female incidence differences were also noted across race and age groups. These results provide strong evidence that the fundamental biology of sex differences affects cancers of all types.
This study represents the most recent and comprehensive reporting of sex differences in cancer incidence and survival in the United States. Identifying disadvantaged groups is critical as it can provide useful information to improve cancer survival, as well as to better understand the etiology and pathogenesis of specific cancers.
Abstract
Background
Meningioma incidence increases significantly with age. In the expanding elderly population, we lack complete understanding of population-based trends in meningioma ...incidence/survival. We provide an updated, comprehensive analysis of meningioma incidence and survival for individuals aged over 65.
Methods
Data were obtained from the Central Brain Tumor Registry of the United States (CBTRUS) from 2005–2015 for nonmalignant and malignant meningioma. Age-adjusted incidence rates per 100000 person-years were analyzed by age, sex, race, ethnicity, location, and treatment modalities. Survival was analyzed using Kaplan–Meier and multivariable Cox proportional hazards models for a subset of CBTRUS data.
Results
Nonmalignant meningioma incidence doubled from adults age 65–69 years to adults over age 85 years and was significantly greater in females than males for all ages. Malignant meningioma incidence did not differ by sex for any age grouping. Nonmalignant and malignant meningioma incidence was significantly greater in black populations versus others. Nonmalignant meningioma survival was worse with age, in black populations, and in males, including when analyzed by 5-year age groups. Surgical resection and radiation did not improve survival compared with resection alone in nonmalignant meningioma.
Conclusions
This study reports increasing nonmalignant meningioma incidence in the elderly, increased incidence in black populations, and in females. In contrast, malignant meningioma incidence did not differ between sexes. Risk of death was higher for black individuals and males. Additionally, radiation did not confer a survival advantage when combined with resection for nonmalignant meningioma. Thus, we identify clinically relevant discrepancies in meningioma incidence/survival that require further study.
Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome‐wide association study in African ...ancestry women with 755 EOC cases, including 537 high‐grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10−6), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3′ of UGT2A2) and rs142091544 (5 kb 5′ of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5′ of follistatin FST), rs57403204 (81 kb 3′ of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5′ of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3′ of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow‐up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry‐derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry.
What's new?
Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. To date, genome‐wide association studies (GWAS) have identified 30 common, low‐penetrant EOC susceptibility alleles. However, most studies were restricted to European ancestry women, and it remains to be determined whether there is any concordance among women of African descent. In this first GWAS conducted in women of African ancestry, the authors report ten novel associated SNPs. The results also suggest there may be some shared genetic architecture between women of European and African ancestry for susceptibility to ovarian cancer.
Background Most melanoma studies use data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program or individual cancer registries. Small numbers of melanoma cases have ...limited in-depth analyses for all racial and ethnic groups. Objective We sought to describe racial and ethnic variations in melanoma incidence and survival. Methods Incidence for invasive melanoma and 5-year melanoma-specific survival were calculated for whites, blacks, American Indians/Alaskan Natives, Asians/Pacific Islanders (API), and Hispanics using data from 38 population-based cancer registries. Results Incidence rates of melanoma were significantly higher for females than males among whites and Hispanics under 50 years of age and APIs under 40 years of age. White and black patients were older (median age: 59-63 years) compared with Hispanics, American Indians/Alaskan Natives, and API (median age: 52-56 years). The most common histologic type was acral lentiginous melanoma among blacks and superficial spreading melanoma among all other racial and ethnic groups. Hispanics had the highest incidence rate of acral lentiginous melanoma, significantly higher than whites and API. Nonwhites were more likely to have advanced and thicker melanomas at diagnosis and lower melanoma-specific survival compared with whites. Limitations Over 50% of melanoma cases did not have specified histology. The numbers of nonwhite patients were still relatively small despite broad population coverage (67% of United States). Conclusions Racial and ethnic differences in age at melanoma diagnosis, anatomic sites, and histologic types suggest variations in etiologic pathways. The high percentages of advanced and thicker melanomas among nonwhites highlight the need to improve melanoma awareness for all race and ethnicity in the United States.
There is a paucity of population-based data evaluating the incidence of vestibular schwannomas according to age, gender, race, and ethnicity. Such data are necessary to assess the burden of ...vestibular schwannomas on varying populations and to inform future research and healthcare planning. The Central Brain Tumor Registry of the United States, which contains the largest aggregation of population-based data on the incidence of primary central nervous system tumors in the US, was used. Age-adjusted incidence rates and incidence rate ratios (IRR) of vestibular schwannomas from 2004 to 2010 were calculated by age at diagnosis, gender, race, and ethnicity. Annual percent change (APC) was calculated using Joinpoint to characterize temporal trends. From 2004 to 2010, there were 23,729 newly diagnosed vestibular schwannomas in the US; overall incidence was 1.09 per 100,000 population. Incidence was stable over time (APC −0.41 %, 95 % confidence interval −3.4, 2.7). Incidence increased with age to a peak of 2.93 per 100,000 in the 65–74 year old age group. Overall, there was no difference in incidence by gender. Compared to Whites, incidence was highest in Asian Pacific Islanders (IRR 1.37, p < 0.001) and lowest in African Americans (IRR 0.36, p < 0.001). Incidence was lower in Hispanics than non-Hispanics (IRR 0.69, p < 0.001). Over 3300 vestibular schwannomas are diagnosed per year in the US and incidence is 1.09 per 100,000 population. Incidence increases with age up to the 65–74 year old age group. Incidence is higher in Asian Pacific Islanders and lower in African Americans and Hispanics.
Longitudinal and behavioral preclinical animal studies generate complex data, which may not be well matched to statistical approaches common in this literature. Analyses that do not adequately ...account for complexity may result in overly optimistic study conclusions, with consequences for reproducibility and translational decision-making. Recent work interrogating methodological shortcomings in animal research has not yet comprehensively investigated statistical shortcomings in the analysis of complex longitudinal and behavioral data. To this end, the current cross-sectional meta-research study rigorously reviewed published mouse or rat controlled experiments for motor rehabilitation in three neurologic conditions to evaluate statistical choices and reporting. Medline via PubMed was queried in February 2020 for English-language articles published January 1, 2017- December 31, 2019. Included were articles that used rat or mouse models of stroke, Parkinson's disease, or traumatic brain injury, employed a therapeutic controlled experimental design to determine efficacy, and assessed at least one functional behavioral assessment or global evaluation of function. 241 articles from 99 journals were evaluated independently by a team of nine raters. Articles were assessed for statistical handling of non-independence, animal attrition, outliers, ordinal data, and multiplicity. Exploratory analyses evaluated whether transparency or statistical choices differed as a function of journal factors. A majority of articles failed to account for sources of non-independence in the data (74-93%) and/or did not analytically account for mid-treatment animal attrition (78%). Ordinal variables were often treated as continuous (37%), outliers were predominantly not mentioned (83%), and plots often concealed the distribution of the data (51%) Statistical choices and transparency did not differ with regards to journal rank or reporting requirements. Statistical misapplication can result in invalid experimental findings and inadequate reporting obscures errors. Clinician-scientists evaluating preclinical work for translational promise should be mindful of commonplace errors. Interventions are needed to improve statistical decision-making in preclinical behavioral neurosciences research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Germline DNA copy number variation (CNV) is a ubiquitous source of genetic variation and remains largely unexplored in association with epithelial ovarian cancer (EOC) risk.
CNV was quantified in the ...DNA of approximately 3,500 cases and controls genotyped with the Illumina 610k and HumanOmni2.5M arrays. We performed a genome-wide association study of common (>1%) CNV regions (CNVRs) with EOC and high-grade serous (HGSOC) risk and, using The Cancer Genome Atlas (TCGA), performed
analyses of tumor-gene expression.
Three CNVRs were associated (
< 0.01) with EOC risk: two large (∼100 kb) regions within the 610k set and one small (<5 kb) region with the higher resolution 2.5M data. Large CNVRs included a duplication at
(OR = 2.57;
= 0.001) and a deletion at
(OR = 1.90;
= 0.007) that were strongly associated with HGSOC risk (OR = 3.02;
= 8.98 × 10
). Somatic
alterations correlated with
expression in tumors (
= 2.94 × 10
). An intronic
deletion was associated with reduced EOC risk (OR = 0.33;
= 9.5 × 10
), and somatic deletions correlated with
downregulation (
= 7.05 × 10
). Five CNVRs were associated with HGSOC, including two reduced-risk deletions: one at 1p36.33 (OR = 0.28;
= 0.001) that correlated with lower
expression in TCGA tumors (
= 2.7 × 10
), and another at 8p21.2 (OR = 0.52;
= 0.002) that was present somatically where it correlated with lower
expression (
= 5.9 × 10
).
Though CNV appears to not contribute largely to EOC susceptibility, a number of low-to-common frequency variants may influence the risk of EOC and tumor-gene expression.
Further research on CNV and EOC susceptibility is warranted, particularly with CNVs estimated from high-density arrays.
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