Summary Background Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We ...undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer. Methods Data from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models. Findings 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 20·2% of 674 cases vs 818 6·2% of 13 226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p<0·0001), low-grade serous (31 9·2% of 336 cases, 2·11, 1·39–3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 13·9% of 1220 cases, 2·04, 1·67–2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 6·0% of 516 cases, 1·02, 0·69–1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 7·1% of 3659 cases, 1·13, 0·97–1·32, p=0·13), or borderline tumours of either subtype (serous 103 9·0% of 1140 cases, 1·20, 0·95–1·52, p=0·12, and mucinous 65 8·5% of 767 cases, 1·12, 0·84–1·48, p=0·45). Interpretation Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer. Funding Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.
Abstract
Massive burn injuries are a unique patient population with unique treatment paradigms. Data from 155 adult patients, admitted from 2009 to 2019, with >50% total body surface area burns ...(TBSA) were collected and analyzed. Average burn size was 70% TBSA and 63% had a concomitant inhalation injury. Approximately 30% of patients (46/155) transitioned to comfort care-only measures within 24 hours of admission. Standard treatment patients were younger (37 ± 13 vs 60 ± 19 years; p < .00001), male (94% vs 28%; p = .001) and had smaller TBSA (66 ± 13 vs 80 ± 16; p < .00001). Of the standard treatment group, 72 (66%) survived to discharge. Survivors had smaller TBSA (64 ± 13 vs 71 ± 13; p = .003), less third-degree TBSA (48 ± 25 vs 71 ± 13; p = .003) and lower incidence of renal failure requiring dialysis (22% vs 73%, p < .00001). Multivariate regression analysis showed that age (OR 1.05; p = .025), total TBSA (OR 1.07; p = .005), and renal failure (OR 10.2; p = .00005) were independently associated with mortality. Inhalation injury was not significantly associated with mortality. About 23% (35/155) of patients had a psychiatric condition on admission and 19% (30/155) of patients were burned attempting suicide. Patients with psychiatric conditions spent more time in the hospital (62 vs 30 days; p = .004), more time on ventilator (31 vs 12 days; p = .046), underwent more surgery (4 vs 2 operations, p = .03), and were less likely to die (34% vs 59%; p = .02). In summary, age, burn size, and renal failure were independently associated with mortality, with renal failure being the strongest factor. Psychiatric conditions are prevalent pre-injury and tend to require more inpatient care.
Ovarian cancer is the most lethal gynecologic malignancy in both African-American and white women. Although prevalences of many ovarian cancer risk factors differ markedly between African Americans ...and whites, there has been little research on how the relative contributions of risk factors may vary between racial/ethnic groups. Using data from a North Carolina case-control study (1999–2008), the authors conducted unconditional logistic regression analyses to calculate odds ratios and 95% confidence intervals for ovarian cancer risk factors in African-American (143 cases, 189 controls) and white (943 cases, 868 controls) women and to test for interactions by race/ethnicity. They also calculated attributable fractions within each racial/ethnic group for the modifiable factors of pregnancy, oral contraceptive use, tubal ligation, and body mass index. Many risk factors showed similar relations across racial/ethnic groups, but tubal ligation and family history of breast or ovarian cancer showed stronger associations among African Americans. Younger age at menarche was associated with risk only in white women. Attributable fractions associated with tubal ligation, oral contraceptive use, and obesity were markedly higher for African Americans. The relative importance of ovarian cancer risk factors may differ for African-American women, but conclusions were limited by the small sample. There is a clear need for further research on etiologic factors for ovarian cancer in African-American women.
Ovarian cancer is most frequently diagnosed in postmenopausal women; however, the strongest risk predictors, pregnancy and oral contraceptive use, occur in most women in their twenties and thirties. ...Relatively few studies have examined how reproductive risk factors vary between pre- and postmenopausal ovarian cancer. The authors used data from a population-based, case-control study of ovarian cancer (896 cases, 967 controls) conducted in North Carolina from 1999 to 2006. Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Inverse associations with ovarian cancer were observed with duration of oral contraceptive use, later age at last use, and more recent use among premenopausal women; no significant associations were found for postmenopausal women. Analyses limited to oral contraceptive users showed that duration was a more significant predictor of risk than was timing of use. Parity was inversely associated with premenopausal but not postmenopausal ovarian cancer. Later age at pregnancy was associated with reduced risk for both pre- and postmenopausal women. Analyses among parous women showed that pregnancy timing was a stronger risk predictor than number of pregnancies. Findings suggest that associations between ovarian cancer and reproductive characteristics vary by menopausal status. Additional research is needed to further elucidate risk factors for postmenopausal disease.
We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study ...(NCOCS), a population-based, case-control study.
The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, non-Hispanic race. Statistical analysis was two staged: a screen using marginal Bayes factors (BFs) for 484 SNPs and a modeling stage in which we calculated multivariate adjusted posterior probabilities of association for 77 SNPs that passed the screen. These probabilities were conditional on subject age at diagnosis/interview, batch, a DNA quality metric and genotypes of other SNPs and allowed for uncertainty in the genetic parameterizations of the SNPs and number of associated SNPs. Six SNPs had Bayes factors greater than 10 in favor of an association with invasive serous ovarian cancer. These included rs5762746 (median OR(odds ratio)(per allele) = 0.66; 95% credible interval (CI) = 0.44-1.00) and rs6005835 (median OR(per allele) = 0.69; 95% CI = 0.53-0.91) in CHEK2, rs2078486 (median OR(per allele) = 1.65; 95% CI = 1.21-2.25) and rs12951053 (median OR(per allele) = 1.65; 95% CI = 1.20-2.26) in TP53, rs411697 (median OR (rare homozygote) = 0.53; 95% CI = 0.35 - 0.79) in BACH1 and rs10131 (median OR( rare homozygote) = not estimable) in LIG4. The six most highly associated SNPs are either predicted to be functionally significant or are in LD with such a variant. The variants in TP53 were confirmed to be associated in a large follow-up study.
Based on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results.
Purpose: Previous studies have examined the association between ABO blood group and ovarian cancer risk, with inconclusive results. Methods: In eight studies participating in the Ovarian Cancer ...Association Consortium, we determined ABO blood groups and diplotypes by genotyping 3 SNPs in the ABO locus. Odds ratios and 95 % confidence intervals were calculated in each study using logistic regression; individual study results were combined using random effects meta-analysis. Results: Compared to blood group O, the A blood group was associated with a modestly increased ovarian cancer risk: (OR: 1.09; 95 % CI: 1.01—1.18; p = 0.03). In diplotype analysis, the AO, but not the AA diplotype, was associated with increased risk (AO: OR: 1.11; 95 % CI: 1.01—1.22; p = 0.03; AA: OR: 1.03; 95 % CI: 0.87—1.21; p = 0.76). Neither AB nor the B blood groups were associated with risk. Results were similar across ovarian cancer histologic subtypes. Conclusion: Consistent with most previous reports, the A blood type was associated modestly with increased ovarian cancer risk in this large analysis of multiple studies of ovarian cancer. Future studies investigating potential biologic mechanisms are warranted.
Androgens may play a role in the development of ovarian cancers. Two trinucleotide repeat polymorphisms have been described in exon 1 of the androgen receptor (AR) gene that may affect its function. ...Previous studies of ovarian cancer and AR repeat polymorphisms have been inconsistent.
We analyzed CAG and GGC repeat length polymorphisms in the AR gene using data from a population-based case-control study of ovarian cancer that included 594 cases and 681 controls. Repeat lengths were determined by fluorescent DNA fragment analysis using ABI GeneScan software. Change point models were used to determine appropriate repeat length cutoff points by race (African American versus Caucasian) for both the shorter and longer CAG and GGC repeats.
No relationship was observed between CAG repeat length and ovarian cancer among Caucasians. Among African Americans, having a short repeat length on either allele was associated with a 2-fold increase in ovarian cancer risk (age-adjusted odds ratio, 2.2; 95% confidence interval, 1.1-4.1). Having short CAG repeat lengths for both alleles was associated with a 5-fold increased risk for developing ovarian cancer (age-adjusted odds ratio, 5.4; 95% confidence interval, 1.4-1.7). No relationship with the GGC repeat length polymorphisms was observed.
These results suggest that having a short CAG repeat length in AR increases ovarian cancer risk in African Americans. The failure to observe this relationship in Caucasians may be due to the rarity of such short CAG alleles in this population or could reflect racial differences in disease etiology.
Toxic epidermal necrolysis (TEN) is a potentially fatal disorder that involves large areas of skin desquamation. Patients with TEN are often referred to burn centers for expert wound management and ...comprehensive care. The purpose of this study was to define the presenting characteristics and treatment of TEN before and after admission to regional burn centers and to evaluate the efficacy of burn center treatment for this disorder. A retrospective multicenter chart review was completed for patients admitted with TEN to 15 burn centers from 1995 to 2000. Charts were reviewed for patient characteristics, non-burn hospital and burn center treatment, and outcome. A total of 199 patients were admitted. Patients had a mean age of 47 years, mean 67.7% total body surface area skin slough, and mean Acute Physiology and Chronic Health Evaluation (APACHE II) score of 10. Sixty-four patients died, for a mortality rate of 32%. Mortality increased to 51% for patients transferred to a burn center more than one week after onset of disease. Burn centers and non-burn hospitals differed in their use of enteral nutrition (70 vs 12%, respectively, P < 0.05), prophylactic antibiotics (22 vs 37.9%, P < 0.05), corticosteroid use (22 vs 51%, P < 0.05), and wound management. Age, body surface area involvement, APACHE II score, complications, and parenteral nutrition before transfer correlated with increased mortality. The treatment of TEN differs markedly between burn centers and non-burn centers. Early transport to a burn unit is warranted to improve patient outcome.
OBJECTIVE: To investigate the association between self-reported endometriosis and the putative functional promoter +331C/T single nucleotide polymorphism and the PROGINS allele. DESIGN: Control ...subjects from ovarian cancer case-control studies participating in the international Ovarian Cancer Association Consortium. The majority of controls are drawn from population-based studies. SETTING: An international ovarian cancer consortium including studies from Australia, Europe, and the United States. PATIENT(S): Five thousand eight hundred twelve white female controls, of whom 348 had endometriosis, from eight ovarian cancer case-control studies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genotypes for the +331C/T single nucleotide polymorphism and PROGINS allele and a history of endometriosis. RESULT(S): The occurrence of endometriosis was reduced in women carrying one or more copies of the +331 T allele (odds ratio = 0.65; 95% confidence interval: 0.43–0.98), whereas there was no association between the PROGINS allele and endometriosis (odds ratio = 0.94, 95% confidence interval 0.76–1.16). CONCLUSION(S): Additional studies of the +331C/T variant are warranted given the current finding and the equivocal results of previous studies. The +331 T allele has been shown to result in a reduced progesterone (P) receptor A to P receptor B ratio, and if the observed association with endometriosis is confirmed it would suggest that this ratio is important for this disease.
PDF
