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Background: Cellular metabolism is a tightly controlled process during which cell growth and survival are maintained. Lung cancer is a disease with clear sex differences, where female patients have better survival rates than males. Evidence of sex differences is demonstrated in cancer risk, prognosis and response to different therapies, yet a sex-specific approach to cancer studies is not widely considered. These different tumour characteristics attributed to sex that impact disease outcome, including constitutional genetic and somatic molecular differences, make it essential to assess viral and hormonal influences. Methods: In silico analysis of lung adenocarcinoma (LUAD) TCGA data, including K-means clustering algorithm, dimensional reduction with principal component analysis and differential expression analysis using EdgeR (p < 0.05), were used to explore some robust sex differences in LUAD that exist in core signalling pathways and metabolic processes between males and females. The correlation of differentially expressed genes (DEGs) expression with immune abundance in the LUAD cohort was analysed on TIMER2.0 and adjusted by tumour purity utilising Cox proportional hazard. Multiple factorial analysis heatmap visualisation was used to examine endogenous steroid hormonal effects on LUAD patients with different smoking status and age groups. Results: We found 161 DEGs showing key differences in regulation of immune system and cellular homeostasis, key elements of divergent cancer progression, between the two sexes. We also found male and female LUAD patients to favour different metabolic intermediates for energy production to support tumourigenesis. Additionally, high levels of Tregs accompanied by DEGs correlated with better LUAD prognosis, and circulating hormonal transcriptional targets affect proliferation and progression in males and females differently. Finally, we examined the role of oestrogen protection in men and pre-/postmenopausal women. Conclusions: Further studies should focus on sex-specific changes and investigate sex-specific gene regulatory networks of these DEGs. Several lifestyle factors, including tobacco smoking and diet, differ between males and females. These factors might affect metabolic pathways and can influence the activity of epigenetic regulators, resulting in significant global epigenetic changes. [ABSTRACT FROM AUTHOR]

Background Survival from metastatic cutaneous melanoma is substantially lower than for localized disease. Treatments for metastatic melanoma have been limited, but remarkable clinical improvements have been reported in clinical trials in the last decade. We described the characteristics of US patients diagnosed with cutaneous melanoma during 2001-2013 and assessed trends in short-term survival for distant-stage disease. Methods Trends in 1-year net survival were estimated using the Pohar Perme estimator, controlling for background mortality with life tables of all-cause mortality rates by county of residence, single year of age, sex, and race for each year 2001-2013. We fitted a flexible parametric survival model on the log-hazard scale to estimate the effect of race on the hazard of death because of melanoma and estimated 1-year net survival by race. Results Only 4.4% of the 425 915 melanomas were diagnosed at a distant stage, cases diagnosed at a distant stage are more commonly men, older patients, and African Americans. Age-standardized, 1-year net survival for distant-stage disease was stable at approximately 43% during 2001-2010. From 2010 onward, survival improved rapidly, reaching 58.9% (95% confidence interval = 56.6% to 61.2%) for patients diagnosed in 2013. Younger patients experienced the largest improvement. Survival for distant-stage disease increased in both Blacks and Whites but was consistently lower in Blacks. Conclusions One-year survival for distant-stage melanoma improved during 2001-2013, particularly in younger patients and those diagnosed since 2010. This improvement may be a consequence of the introduction of immune-checkpoint-inhibitors and other targeted treatments for metastatic and unresectable disease. Persistent survival inequalities exist between Blacks and Whites, suggesting differential access to treatment. [ABSTRACT FROM AUTHOR]

Globally, age-standardized incidence rates for most cancers at shared sites are substantially and consistently higher in men than in women. Differences in established risk factors are unable to account for much of the sex disparity. We hypothesized that variability in height may be important in explaining sex differences in cancer risk. We included 49 372 men from the Health Professionals Follow-up Study (1986–2014) and 115 612 women from the Nurses' Health Study (1980–2014). Height was reported at baseline and biennial questionnaires were used to collect information on cancer risk factors. We examined the association between sex and cancer incidence at shared anatomic sites using Cox proportional hazards models and performed mediation analysis to determine the percent of the association that was accounted for by height. Over up to 34 years of follow-up, 21 307 incident cases of cancers at shared sites (7705 men, 13 602 women) were documented. After adjusting for major cancer risk factors, men had a 39% increased risk of shared cancers overall (hazard ratio = 1.39; 95% confidence interval = 1.33–1.45) of which 35% (95% confidence interval = 24–46) was mediated by height. The excess risk of cancer for men was also partially explained by height for several specific cancers (gastrointestinal, melanoma, kidney, brain, hematologic). Mediation by height tended to be stronger among never smokers or those who adhered to a healthy lifestyle, and for cancers with fewer known environmental risk factors. Differences in height among men and women partially mediated the association between sex and cancer incidence at several shared sites. Hence, mechanisms underlying the relationship between height and cancer may be important determinants of sex disparities in cancer incidence. • Height explained 35% of the excess risk of cancers at shared sites overall in men after accounting for major cancer risk factors. • Mediation by height tended to be stronger among never smokers or those adhering to healthy lifestyles. • Mechanisms underlying the relationship between height and cancer may be important determinants of sex disparities. [ABSTRACT FROM AUTHOR]

Sex- and gender-informed medicine and science span broad areas: genetics, epigenetics, effects of sex hormones, and immune function, each with implications for cardiovascular disease and cancer. Hence, cancer and cardiovascular disease share risk factors, but the effects of these risk factors are likely not similar for men and women. Beyond the double-edged sword effect of oncological therapies, a bidirectional cross talk between cardiovascular disease and cancer is emerging at multiple levels, ranging from genetic variants to metabolic, endocrine, neurovegetative, and inflammatory processes. [Extracted from the article]

The article focuses on the rising incidence of colorectal cancer among younger men compared to women, indicating the importance of considering patient sex when determining screening age. Topics discussed include the prevalence of precursor lesions like adenomas among younger individuals; changes in adenoma and advanced adenoma prevalence over time; and the need to adjust screening recommendations based on sex and age groups.

The authors, one female, one male, recount their experiences being treated for breast cancer. They describe their diagnoses and treatments, their support of breast cancer fund raising, and the gender differences in the treatment of breast cancer.

Introduction: The prognostic relevance of gender is undetermined in patients with small-cell lung cancer (SCLC). Therefore, we investigated whether gender is a prognostic factor in a SCLC cohort after controlling for confounding factors. Materials and methods: Fifteen prognostic factors were classified into four groups (patient, stage migration, tumor, and treatment). The prognostic relevance of gender was evaluated using propensity score matching, Cox proportional hazards regression, and stepwise fashion adjustments. Results: Of 591 patients with SCLC, 88 were women (14.9%). Women were more likely than men to have no history of smoking (48.9% vs. 2.0%, P < 0.001) and limited disease (48.9% vs. 37.8%, P = 0.050). Women had less progressive disease in M stage than men (52.3% vs. 62.8%, P = 0.031). Women had better survival than men in the entire cohort (median survival times [MSTs] and 95% confidence intervals [CIs]: 9.7 months and 7.8–11.6 for women, 8.0 months and 7.0–8.9 for men, log-rank P = 0.034) and in the matched cohort (MSTs and 95% CIs: 8.8 months and 5.8–11.8 for women, 5.9 months and 4.5–7.4 for men, log-rank P = 0.013). Female gender was a prognostic factor predicting better survival, even after stepwise and full adjustment with all prognostic variables (adjusted hazard ratios and 95% CIs: 0.51 and 0.34–0.77, P = 0.001 for entire cohort, 0.42 and 0.24–0.75, P = 0.003 for matched cohort). Conclusions: Our results confirmed that gender is an independent prognostic factor in patients with SCLC. [ABSTRACT FROM AUTHOR]

Gender differences in the incidences of cancers have been found in almost all human cancers. However, the mechanisms that underlie gender disparities in most human cancer types have been under-investigated. Here, we provide a comprehensive overview of potential mechanisms underlying sexual dimorphism of each cancer regarding sex hormone signaling. Fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of precision medicine. Our discussions of potential mechanisms underlying sexual dimorphism in each cancer will be instructive for future cancer research on gender disparities. [ABSTRACT FROM AUTHOR]

Purpose: Evidence to date on the unique female determinants of cardiovascular risk is inadequate. Positron Emission Tomography (PET) is considered to have the highest accuracy for the assessment of myocardial perfusion in patients with suspected coronary artery disease (CAD), but its long-term prognostic accuracy in women has not been established.Methods: A total of 619 consecutive patients (138 women, mean age 60.0 ± 11.8 years) underwent clinically indicated 13N-ammonia PET at our institution and were followed up (median 5.7 years) for major adverse cardiovascular events (MACE) including cardiac death, nonfatal myocardial infarction, hospitalization for any cardiac reason and late revascularization.Results: During follow-up, 271 patients had at least one cardiac event, including 64 cardiac deaths and 33 nonfatal myocardial infarctions. In both women and men, abnormal myocardial perfusion was associated with reduced event-free survival (log rank p < 0.001). In women, abnormal myocardial perfusion was associated with a higher risk of a worse outcome than in men (adjusted HR 4.1, 95% CI 1.8-9.0 in women; HR 2.4, 95% CI 1.5-3.8 in men; pinteraction < 0.001). In contrast, abnormal coronary flow reserve (CFR) was a significant predictor of 10-year MACE in men (p = 0.006) but not in women (p = NS). Accordingly, an interaction term of sex and abnormal myocardial perfusion or CFR was significant (p < 0.001).Conclusion: While perfusion findings in 13N-ammonia PET provide effective risk stratification in women and men, CFR adds incremental prognostic value for long-term cardiac outcomes only in men. Refined strategies in noninvasive imaging are needed in women to improve CAD risk prediction. [ABSTRACT FROM AUTHOR]

Abstract: Sex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal‐in‐maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. The frequency and potential role of these cells has not been investigated in brain tumors. We therefore selected two common primary adult brain tumors for this purpose: meningioma, which is sex hormone responsive and has a higher incidence in women, and glioblastoma, which is sex hormone independent and occurs more commonly in men. Quantitative PCR was used to detect the presence of male DNA in tumor samples from women with a positive history of male pregnancy and a diagnosis of either glioblastoma or meningioma. Fluorescence in situ hybridization for the X and Y chromosomes was used to verify the existence of intact male cells within tumor tissue. Fetal microchimerism was found in approximately 80% of glioblastoma cases and 50% of meningioma cases. No correlations were identified between the presence of microchimerism and commonly used clinical or molecular diagnostic features of disease. The impact of fetal microchimeric cells should be evaluated prospectively. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association of age and sex on survival in non-metastatic colorectal cancer (CRC) patients and to identify groups at high risk for poor outcomes. Materials and methods: We performed a retrospective analysis of 5,047 non-metastatic CRC patients from 2008 to 2013. Data regarding age at diagnosis; gender; tumor site; tumor stage; differentiation; lymphatic, neural or vascular invasion; and survival outcomes were collected. Patients were stratified into 10-year age groups (≤35, 36–45, 46–55, 56–65, 66–75, >75) and then further analyzed in three age groups (≤35, 36–75, >75). Disease-free survival (DFS) and overall survival (OS) were evaluated using univariate and multivariate Cox regression models. Results: Of the 5,047 eligible patients, 41.3% were female. The tumor stages were balanced between the genders. In the female patients, the tumor stages were similarly distributed among the different age groups, while younger male patients were diagnosed with more advanced disease (P<0.001 for trend). When stratified into three age groups, young females experienced significantly poorer survival than young males (DFS: hazard ratio [HR]=1.85 [1.04–3.30], OS: HR=2.65 [1.11–6.34]). After adjusting for tumor stage, site, differentiated grade and lymphatic or vascular invasion status, females ≤35 and >75 had shorter DFS than patients between 36 and 75 years old (HR=1.57 [1.03–2.38] and HR=1.51 [1.11–2.05, respectively]), while there was no difference in DFS between females ≤35 and those >75. For male patients, older age was associated with poorer OS after the same adjustment. Conclusion: Young female CRC patients (≤35 years old) had the poorest DFS and quite poor OS compared to the other age groups. This emphasizes the need for health care providers to have a heightened awareness and to conduct further research when caring for young female CRC patients. [ABSTRACT FROM AUTHOR]

Background: Relatively few studies have analyzed the mortality of follicular lymphoma (FL) patients in comparison with a sex- and age-matched general population. This study analyzed the overall survival (OS) of patients with FL and compared their survival with the expected survival of a general population.Methods: Patients diagnosed with FL were prospectively enrolled from 1980 to 2013. Standardized mortality ratios (SMRs) were obtained from yearly sex- and age-specific mortality rates in Spain, and OS was compared with age- and sex-matched general population data.Results: A total of 1074 patients with newly diagnosed FL were enrolled. The median OS was 231 months (95% confidence interval [CI], 195-267 months). Event-free survival at 12 months (EFS12) and event-free survival at 24 months (EFS24) were associated with an increased probability of early death, with an SMR of 10.27 (95% CI, 8.26-12.77) for EFS12. The overall SMR, including all causes of death, was 2.55 (95% CI, 2.23-2.92), and it was higher for women (SMR, 3.02; 95% CI, 2.48-3.67) and young adults (SMR, 6.01; 95% CI, 3.13-11.55). More than 10 years after the diagnosis, mortality rates for FL patients were lower than those for the general population (SMR, 0.47; 95% CI, 0.28-0.78). When FL was excluded as a cause of death, the overall SMR was 1.35 (95% CI, 1.11-1.65) without a statistically significant mortality increase in the >60-year-old group in comparison with age- and sex-matched general population data. More than 15% of the patients included in the study (n = 158) had more than 10 years of follow-up.Conclusions: EFS12 and EFS24 predict an early increase in mortality. The long-term SMR, over the course of 10 years of follow-up, shows that patients with FL have a risk of dying similar to that of a sex- and age-matched general population. Cancer 2017;123:3709-3716. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro , estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo . Our finding indicates that estrogen may play a role in gut tight junction expression and permeability. [ABSTRACT FROM AUTHOR]

Sex-associated differences in bone metastasis formation from breast, lung, and prostate cancer exist in clinical studies, but have not been systematically reviewed. Differences in the bone marrow niche can be attributed to sexual dimorphism, to genetic variations that affect sex hormone levels, or to the direct effects of sex hormones, natural or exogenously delivered. This review describes the present understanding of sex-associated and sex hormone level differences in the marrow niche and in formation of bone metastasis during the transition of these three cancers from treatable disease to an often untreatable, lethal metastatic one. Our purpose is to provide insight into some underlying molecular mechanisms for hormonal influence in bone metastasis formation, and to the potential influence of sexual dimorphism, genetic differences affecting sex assignment, and sex hormone level differences on the bone niche and its favorability for metastasis formation. We reviewed publications in PubMed and EMBASE, including full length manuscripts, case reports, and clinical studies of relevance to our topic. We focused on bone metastasis formation in breast, lung, and prostate cancer because all three commonly present with bone metastases. Several clear observations emerged. For breast cancer bone metastasis formation, estrogen receptor (ER) signaling pathways indicate a role for ER beta (ERβ). Estrogen influences the bone microenvironment, creating and conditioning a favorable niche for colonization and breast cancer progression. For lung cancer, studies support the hypothesis that females have a more favorable bone microenvironment for metastasis formation. For prostate cancer, a decrease in the relative androgen to estrogen balance or a "feminization" of bone marrow favors bone metastasis formation, with a potentially important role for ERβ that may be similar to that in breast cancer. Long-term estrogen administration or androgen blockade in males may feminize the bone marrow niche to one more favorable for bone metastases in prostate cancer. Administration of androgens in females, especially combined with mastectomy, may reduce risk of developing bone metastatic breast cancer. We conclude that it should be considered that females, those with female-leaning genetic variations, or hormonal states that feminize the bone marrow, may offer favorable sites for bone metastases. [ABSTRACT FROM AUTHOR]

Background: Interval colorectal cancer (CRC) accounts for 3% to 8% of all cases of CRC in the United States. Data on interval CRC by race/ethnicity are scant.Objective: To examine whether risk for interval CRC among Medicare patients differs by race/ethnicity and whether this potential variation is accounted for by differences in the quality of colonoscopy, as measured by physicians' polyp detection rate (PDR).Design: Population-based cohort study.Setting: Medicare program.Participants: Patients aged 66 to 75 years who received colonoscopy between 2002 and 2011 and were followed through 2013.Measurements: Kaplan-Meier curves and adjusted Cox models were used to estimate cumulative probabilities and hazard ratios (HRs) of interval CRC, defined as a CRC diagnosis 6 to 59 months after colonoscopy.Results: There were 2735 cases of interval CRC identified over 235 146 person-years of follow-up. A higher proportion of black persons (52.8%) than white persons (46.2%) received colonoscopy from physicians with a lower PDR. This rate was significantly associated with interval CRC risk. The probability of interval CRC by the end of follow-up was 7.1% in black persons and 5.8% in white persons. Compared with white persons, black persons had significantly higher risk for interval CRC (HR, 1.31 [95% CI, 1.13 to 1.51]); the disparity was more pronounced for cancer of the rectum (HR, 1.70 [CI, 1.25 to 2.31]) and distal colon (HR, 1.45 [CI, 1.00 to 2.11]) than for cancer of the proximal colon (HR, 1.17 [CI, 0.96 to 1.42]). Adjustment for PDR did not alter HRs by race/ethnicity, but differences between black persons and white persons were greater among physicians with higher PDRs.Limitation: Colonoscopy and polypectomy were identified by using billing codes.Conclusion: Among elderly Medicare enrollees, the risk for interval CRC was higher in black persons than in white persons; the difference was more pronounced for cancer of the distal colon and rectum and for physicians with higher PDRs.Primary Funding Source: American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is the third most commonly diagnosed malignancy and the fourth leading cause of cancer-related death globally. It is the second most common cancer among both males and females in Malaysia. The economic burden of colorectal cancer is likely to increase over time owing to its current trend and aging population. Cancer survival analysis is an essential indicator for early detection and improvement in cancer treatment. However, there was a scarcity of studies concerning survival of colorectal cancer patients as well as its predictors. Therefore, we aimed to determine the 1-, 3- and 5-year survival rates, compare survival rates among ethnic groups and determine the predictors of survival among colorectal cancer patients.Methods: This was an ambidirectional cohort study conducted at the University Malaya Medical Centre (UMMC) in Kuala Lumpur, Malaysia. All Malaysian citizens or permanent residents with histologically confirmed diagnosis of colorectal cancer seen at UMMC from 1 January 2001 to 31 December 2010 were included in the study. Demographic and clinical characteristics were extracted from the medical records. Patients were followed-up until death or censored at the end of the study (31st December 2010). Censored patients' vital status (whether alive or dead) were cross checked with the National Registration Department. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Log-rank test was used to compare the survival rates, while Cox proportional hazard regression analysis was carried out to determine the predictors of 5-year colorectal cancer survival.Results: Among 1212 patients, the median survival for colorectal, colon and rectal cancers were 42.0, 42.0 and 41.0 months respectively; while the 1-, 3-, and 5-year relative survival rates ranged from 73.8 to 76.0%, 52.1 to 53.7% and 40.4 to 45.4% respectively. The Chinese patients had the lowest 5-year survival compared to Malay and Indian patients. Based on the 814 patients with data on their Duke's staging, independent predictors of poor colorectal cancer (5-year) survival were male sex (Hazard Ratio [HR]: 1.41; 95% CI: 1.12, 1.76), Chinese ethnicity (HR: 1.41; 95% CI: 1.07,1.85), elevated (≥ 5.1 ng/ml) pre-operative carcino-embryonic antigen (CEA) level (HR: 2.13; 95% CI: 1.60, 2.83), Duke's stage C (HR: 1.68; 95% CI: 1.28, 2.21), Duke's stage D (HR: 4.61; 95% CI: 3.39, 6.28) and emergency surgery (HR: 1.52; 95% CI: 1.07, 2.15).Conclusions: The survival rates of colorectal cancer among our patients were comparable with those of some Asian countries but lower than those found in more developed countries. Males and patients from the Chinese ethnic group had lower survival rates compared to their counterparts. More advanced staging and late presentation were important predictors of colorectal cancer survival. Health education programs targeting high risk groups and emphasizing the importance of screening and early diagnosis, as well as the recognition of symptoms and risk factors should be implemented. A nationwide colorectal cancer screening program should be designed and implemented to increase early detection and improve survival outcomes. [ABSTRACT FROM AUTHOR]

Background The incidence of thyroid cancer is increasing in men and women. Fine needle aspiration (FNA) is an accepted technique to assess thyroid nodules but is associated with a high rate of non-diagnostic sampling. Purpose To assess the diagnostic performance of ultrasound-guided FNA of thyroid nodules and identify factors associated with non-diagnostic sampling. Material and Methods A retrospective review of thyroid FNAs was performed between 2006 and 2013. Patient demographics, nodule characteristics, procedural technique, cytology, and complications were recorded. Cytology was categorized THY1-5 based on the British Thyroid Association guidelines. Descriptive and multivariable analysis were conducted to identify factors associated with non-diagnostic sampling. Results A total of 724 procedures were identified with 597 (82.5%) in women, and an overall mean age of 40 years (age range, 17-87 years). Factors associated with a non-diagnostic outcome in the multivariable regression analysis included increasing lesion depth (OR, 1.05 per mm; 95% confidence interval [CI], 1.007-1.10), age (OR, 1.012 per year; 95% CI, 1.0-1.025) and number of FNA passes (1 vs. 4+; OR, 6.07; 95% CI, 2.27-16.21). The complication rate was 1.1% related to perilesional hematomas and vaso-vagal episodes. Conclusion Thyroid FNA is a safe and reliable procedure for cytological assessment of thyroid nodules. Deeper nodules and older patients are more likely to have non-diagnostic samples. [ABSTRACT FROM AUTHOR]

Esophageal adenocarcinoma (EA) incidence is 4-8 times higher in men compared with women, yet this imbalance cannot be explained by known risk factors. This issue of The American Journal of Gastroenterology features results from only the second prospective study to assess whether prediagnostic sex steroid hormones underlie sex differences in EA. Xie et al. report that higher concentrations of testosterone and luteinizing hormone were associated with decreased EA risk. While contrary to the long-standing hypothesis that testosterone increases EA risk, these important results lay a foundation for additional studies to further elucidate this intuitive, intriguing, and evolving hypothesis. [ABSTRACT FROM AUTHOR]

The article discusses sex differences in melanoma prognosis, focusing on the X chromosome expression of the gonosomal protein phosphatase 2 regulatory subunit B beta (PPP2R3B) gene in tumor growth inhibition and cell cycle interference. It is noted that PPP2R3B expression is lower at the pseudoautosomal region (PAR) of the Y chromosome, leading to poorer metastasis-free survival in males. Topics include the impact of the PPP2R3B protein PR70 on DNA replication and cell division cycle in melanoma

Background Chordomas are rare malignancies that primarily affect adults, but also rarely affect pediatric patients. We compared the imaging appearance, demographic and anatomic distributions of adult and pediatric chordomas in a large cohort. Methods We performed a retrospective review of medical records of 220 subjects with histologically confirmed chordomas of the axial skeleton and pre-treatment magnetic resonance imaging studies. Age, sex, type of chordoma (conventional, chondroid or dedifferentiated), the anatomic location of the chordoma, as well as whether the lesion was primarily extra-osseous were recorded. Pediatric subjects were less than 21 years at the time of diagnosis. Binomial two-sample tests of proportions and Fisher’s exact tests were used to compare proportions between the pediatric and adult subjects. Results Fifty six pediatric subjects (58.9 % female) and 164 adult subjects (42.1 % female) were identified. The proportion of female subjects with chordomas was significantly higher in the pediatric cohort compared to the adult cohort (P = 0.04). Most chordomas occur in Caucasians, however African-Americans were more represented in the pediatric cohort than in the adult cohort (P = 0.01). 69.6 % (39/56) of the pediatric chordomas involved the clivus/skull base and cervical spine compared to 29.3 % (48/164) of the adult chordomas (P = 1.99 × 10−7). Only 1.8 % (1/56) of the pediatric chordomas was in the sacrococcygeal region compared to 36.0 % (59/164) of the adult chordomas (P = 2.55 × 10−8). In cases where pre-treatment imaging was available, 93.8 % (16/17) of pediatric chordomas were predominantly extra-osseous compared to 76.7 % (46/60) of adult chordomas (P = 0.17). Conclusions Pediatric chordomas more often affect females and occur most frequently at the craniocervical junction with decrease in incidence distally in the spine, whereas adult chordomas most frequently involve the craniocervical and sacrococcygeal regions. [ABSTRACT FROM AUTHOR]

Background: A decrease in cancer mortality has been reported in the United States, Europe, and other high-income regions during the last two decades. Whether similar trends apply to low-to-middle income countries--and globally--is unclear. Design: The aim of this descriptive study is to compare cancer mortality in all countries with high- or intermediate-quality data on death certificates according to the World Health Organization (WHO) mortality database for the years 2000 through 2010. We included 60 countries in the analysis and calculated age-adjusted mortality rates for all cancer combined and for the commonest cancers worldwide: lung, stomach, breast, colorectal, uterine, and prostate. Results: A decrease in overall cancer mortality rate of ~1% per year was observed in higher and lower income regions and in both sexes. In 2010, 696 000 cancer deaths were avoided on a global scale compared with 2000 rates (426 000 in men, 271 000 in women). However, the mortality of liver cancer in both sexes and lung cancer in females increased in many countries'. Conclusions: The individual risk of dying from cancer decreased in all countries with reliable data. This decrease was chiefly due to favorable trends in the commonest specific cancers. Liver cancer in both sexes and lung cancer in women, which show increasing mortality rates, constitute a priority for prevention and further research. [ABSTRACT FROM AUTHOR]

Background: Cancer care is currently the most important medical issue in Japan. Total pain of cancer patients consists of a combination of four factors: physical, psychological, social distress, and spiritual pain. Previous studies showed female cancer patients ask for more psychological support and seem to suffer different types of distress compared with male patients, for example, appearance-related symptoms. However, other factors of cancer distress related to gender have not been defined comprehensively. The aim of this study is to clarify the gender differences in cancer distress types in order to elucidate the measures that should be taken in Japan to improve the quality of whole cancer care based on gender-based medicine. Methods: The data of new patients who had visited the psycho-oncology outpatient service of Kinki University Hospital during the period of May 2013 to October 2015 were collected. Demographic factors and all assessed items were extracted from the patients' medical charts retrospectively. Based on an inquiry of cancer patients in 2010, each item representing the four factors of "total pain" of cancer patients was chosen, i.e., physical distress (pain, changes in appearance), psychological distress (anxiety, depression), social distress (family problems, job-related problems), and spiritual pain; together with sexuality issues, and answers were analyzed. Hospital Anxiety Depression Scale (HADS) was used for the assessment of psychological distress. Chi-square test and Fisher's exact test were performed for gender differences in the cancer distress types. Pearson's analysis and multiple logistic regression analysis were performed for the association of gender with each item. Results: The data of 101 cancer patients were analyzed and there were more female patients than male patients (female: male ratio = 71:30). Female cancer patients were more likely to suffer from psycho-social issues such as changes in appearance, family problems and sexuality issues than male patients, and male patients were more likely to have spiritual pain. Conclusions: There were gender differences in the distress types of cancer patients. In order to improve the quality of whole cancer care, more intensive intervention by medical professionals and social support is needed from the viewpoint of gender-based medicine and psycho-oncology. [ABSTRACT FROM AUTHOR]

Aims Seven cases of primary giant cell carcinomas of the lung are presented. Methods and results The patients were five women and two men between the ages of 48 and 72 years (average: 63 years). Clinically, the patients presented with symptoms of cough, chest pain, dyspnoea and general malaise. Diagnostic imaging revealed the presence of intrapulmonary masses; five tumours were located in the right lung and two in the left, with a general predilection for the upper lobes. All patients underwent surgical resection and staging of their tumours. Five patients were staged as T2 and T3 with nodal metastasis, while two patients in stages T1 and T3, respectively, had no nodal disease. Histologically, the giant cells were typed as syncytiotrophoblast-like or 'null type', according to the expression of β-human chorionic gonadotrophin or expression of cytokeratin alone. Follow-up information revealed that five patients died within a period of 1-3 years, while two patients remain alive between 1 and 3 years. Conclusions The cases presented herein highlight the importance of separating these tumours from the group of sarcomatoid carcinomas and analysing them carefully by immumohistochemical means, as we believe that these neoplasms represent a specific tumour entity. [ABSTRACT FROM AUTHOR]

This article provides an overview of the current literature on seven cancer sites that may disproportionately affect lesbian, gay, bisexual, transgender/transsexual, and queer/questioning (LGBTQ) populations. For each cancer site, the authors present and discuss the descriptive statistics, primary prevention, secondary prevention and preclinical disease, tertiary prevention and late-stage disease, and clinical implications. Finally, an overview of psychosocial factors related to cancer survivorship is offered as well as strategies for improving access to care. CA Cancer J Clin 2015;65:384-400. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background. Assessment of progress in cancer control at the population level is increasingly important. Population-based survival trends provide a key insight into the overall effectiveness of the health system, alongside trends in incidence and mortality. For this purpose, we aimed to provide a unique measure of cancer survival. Methods. In this observational study, we analysed trends in survival with population-based data for 7-2 million adults diagnosed with a first, primary, invasive malignancy in England and Wales during 1971-2011 and followed up to the end of 2012. We constructed a survival index for all cancers combined using data from the National Cancer Registry and the Welsh Cancer Intelligence and Surveillance Unit. The index is designed to be independent of changes in the age distribution of patients with cancer and of changes in the proportion of lethal cancers in each sex. We analysed trends in the cancer survival index at 1, 5, and 10 years after diagnosis for the selected periods 1971-72, 1980-81, 1990-91, 2000-01, 2005-06, and 2010-11. We also estimated trends in age-sex-adjusted survival for each cancer. We define the difference in net survival between the oldest (75-99 years) and youngest (15-44 years) patients as the age gap in survival. We evaluated the absolute change (%) in the age gap since 1971. Findings. The overall index of net survival increased substantially during the 40-year period 1971-2011, both in England and in Wales. For patients diagnosed in 1971-72, the index of net survival was 50% at 1 year after diagnosis. 40 years later, the same value of 50% was predicted at 10 years after diagnosis. The average 10% survival advantage for women persisted throughout this period. Predicted 10-year net survival adjusted for age and sex for patients diagnosed between 2010 and 2011 ranged from 1•1% for pancreatic cancer to 98 • 2% for testicular cancer. Net survival for the oldest patients (75-99 years) was persistently lower than for the youngest (15-44 years), even after adjustment for the much higher mortality from causes other than cancer in elderly people. Interpretation. These findings support substantial increases in both short-term and long-term net survival from all cancers combined in both England and Wales. The net survival index provides a convenient, single number that summarises the overall patterns of cancer survival in any one population, in each calendar period, for young and old men and women and for a wide range of cancers with very disparate survival. The persistent sex difference is partly due to a more favourable cancer distribution in women than men. The very wide differences in survival for different cancers, and the persistent age gap in survival, suggest the need for renewed efforts to improve cancer outcomes. Future monitoring of the cancer survival index will not be possible unless the current crisis of public concern about sharing of individual data for public health research can be resolved. Funding Cancer Research UK. [ABSTRACT FROM AUTHOR]

Background: Several regions of the genome show pleiotropic associations with multiple cancers. We sought to evaluate whether 181 single-nucleotide polymorphisms previously associated with various cancers in genome-wide association studies were also associated with melanoma risk. Methods: We evaluated 2,131 melanoma cases and 20,353 controls from three studies in the Population Architecture using Genomics and Epidemiology (PAGE) study (EAGLE-BioVU, MEC, WHI) and two collaborating studies (HPFS, NHS). Overall and sex-stratified analyses were performed across studies. Results: We observed statistically significant associations with melanoma for two lung cancer SNPs in the TERT-CLPTM1L locus (Bonferroni-corrected p<2.8x10-4), replicating known pleiotropic effects at this locus. In sex-stratified analyses, we also observed a potential male-specific association between prostate cancer risk variant rs12418451 and melanoma risk (OR=1.22, p=8.0x10-4). No other variants in our study were associated with melanoma after multiple comparisons adjustment (p>2.8e-4). Conclusions: We provide confirmatory evidence of pleiotropic associations with melanoma for two SNPs previously associated with lung cancer, and provide suggestive evidence for a male-specific association with melanoma for prostate cancer variant rs12418451. This SNP is located near TPCN2, an ion transport gene containing SNPs which have been previously associated with hair pigmentation but not melanoma risk. Previous evidence provides biological plausibility for this association, and suggests a complex interplay between ion transport, pigmentation, and melanoma risk that may vary by sex. If confirmed, these pleiotropic relationships may help elucidate shared molecular pathways between cancers and related phenotypes. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine breast density in relation to breast cancer specific survival and to assess if this potential association was modified by mode of detection. An additional aim was to study whether the established association between mode of detection and survival is modified by breast density. Methods: The study included 619 cases from a prospective cohort, The Malmö Diet and Cancer Study. Breast density estimated qualitatively, was analyzed in relation to breast cancer death, in non-symptomatic and symptomatic women, using Cox regression calculating hazard ratios (HR) with 95% confidence intervals. Adjustments were made in several steps for; diagnostic age, tumour size, axillary lymph node involvement, grade, hormone receptor status, body mass index (baseline), diagnostic period, use of hormone replacement therapy at diagnosis and mode of detection. Detection mode in relation to survival was analyzed stratified for breast density. Differences in HR following different adjustments were analyzed by Freedmans%. Results: After adjustment for age and other prognostic factors, women with dense, as compared to fatty breasts, had an increased risk of breast cancer death, HR 2.56:1.07-6.11, with a statistically significant trend over density categories, p = 0.04. In the stratified analysis, the effect was less pronounced in non-symptomatic women, HR 2.04:0.49-8.49 as compared to symptomatic, HR 3.40:1.06-10.90. In the unadjusted model, symptomatic women had a higher risk of breast cancer death, regardless of breast density. Analyzed by Freedmans%, age, tumour size, lymph nodes, grade, diagnostic period, ER and PgR explained 55.5% of the observed differences in mortality between non-symptomatic and symptomatic cases. Additional adjustment for breast density caused only a minor change. Conclusions: High breast density at diagnosis may be associated with decreased breast cancer survival. This association appears to be stronger in women with symptomatic cancers but breast density could not explain differences in survival according to detection mode. [ABSTRACT FROM AUTHOR]

Background: Changes to sexual wellbeing are acknowledged to be a long-term negative consequence of cancer and cancer treatment. These changes can have a negative effect on psychological well-being, quality of life and couple relationships. Whilst previous conclusions are based on univariate analysis, multivariate research can facilitate examination of the complex interaction between sexual function and psycho-social variables such as psychological wellbeing, quality of life, and relationship satisfaction and communication in the context of cancer, the aim of the present study. Method: Six hundred and fifty seven people with cancer (535 women, 122 men) and 148 partners (87 women, 61 men), across a range of sexual and non-sexual cancers, completed a survey consisting of standardized measures of sexual functioning, depression and anxiety, quality of life, relationship satisfaction, dyadic sexual communication, and self-silencing, as well as ratings of the importance of sex to life and relationships. Results: Men and women participants, reported reductions in sexual functioning after cancer across cancer type, for both people with cancer and partners. Multiple regression analysis examined psycho-social predictors of sexual functioning. Physical quality of life was a predictor for men and women with cancer, and for male partners. Dyadic sexual communication was a predictor for women with cancer, and for men and women partners. Mental quality of life and depression were also predictors for women with cancer, and the lower self-sacrifice subscale of self-silencing a predictor for men with cancer. Conclusion: These results suggest that information and supportive interventions developed to alleviate sexual difficulties and facilitate sexual renegotiation should be offered to men and women with both sexual and non-sexual cancers, rather than primarily focused on individuals with sexual and reproductive cancers, as is the case currently. It is also important to include partners in supportive interventions. Interventions aimed at improving sexual functioning should include elements aimed at improving physical quality of life and sexual communication, with a focus on psychological wellbeing also being important for women with cancer. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is the second most common cause of cancer-related death in males and the fourth in females. Traditional treatment has poor prognosis because of recurrence and systemic side effects. Therefore, the development of new therapeutic strategies is an important issue. Lentivirus-mediated shRNA stably inhibits target genes and can efficiently transduce most cells. Since overexpressed cyclin D1 is closely related to human gastric cancer progression, inhibition of cyclin D1 using specific targeting could be an effective treatment method of human gastric cancer. Methods: The therapeutic effect of lentivirus-mediated shRNA targeting of cyclin D1 (ShCCND1) was analyzed both in vitro and in vivo experiments. Results: In vitro, NCI-N87 cells with downregulation of cyclin D1 by ShCCND1 showed significant inhibition of cell proliferation, cell motility, and clonogenicity. Downregulation of cyclin D1 in NCI-N87 cells also resulted in significantly increased G1 arrest and apoptosis. In vivo, stable NCI-N87 cells expressing ShCCND1 were engrafted into nude mice. Then, the cancer-growth inhibition effect of lentivirus was confirmed. To assess lentivirus including ShCCND1 as a therapeutic agent, intratumoral injection was conducted. Tumor growth of the lentivirus-treated group was significantly inhibited compared to growth of the control group. These results are in accordance with the in vitro data and lend support to the mitotic figure count and apoptosis analysis of the tumor mass. Conclusion: The lentivirus-mediated ShCCND1 was constructed, which effectively inhibited growth of NCI-N87-derived cancer both in vitro and in vivo. The efficiency of shRNA knockdown and variation in the degree of inhibition is mediated by different shRNA sequences and cancer cell lines. These experimental results suggest the possibility of developing new gastric cancer therapies using lentivirus-mediated shRNA. [ABSTRACT FROM AUTHOR]

The incidence and mortality rates of many non-reproductive human cancers are generally higher in males than in females. However, the immunological mechanism underlying sexual differences in cancers remains elusive. Here, we demonstrated that sex-related differences in tumor burden depended on adaptive immunity. Male CD8+ T cells exhibited impaired effector and stem cell-like properties compared with female CD8+ T cells. Mechanistically, androgen receptor inhibited the activity and stemness of male tumor-infiltrating CD8+ T cells by regulating epigenetic and transcriptional differentiation programs. Castration combined with anti-PD-L1 treatment synergistically restricted tumor growth in male mice. In humans, fewer male CD8+ T cells maintained a stem cell-like memory state compared with female counterparts. Moreover, AR expression correlated with tumor-infiltrating CD8+ T cell exhaustion in cancer patients. Our findings reveal sex-biased CD8+ T cell stemness programs in cancer progression and in the responses to cancer immunotherapy, providing insights into the development of sex-based immunotherapeutic strategies for cancer treatment. [Display omitted] • CD8+ T cell stemness programs confer sex differences in antitumor immunity • AR signaling undermines the preservation of stem cell-like state in male CD8+ T cells • Ablation of AR signaling synergizes with T cell-based cancer immunotherapy • AR expression positively correlates with CD8+ T cell exhaustion in human cancers Most non-reproductive human cancers exhibit sex differences, but the underlying immunological mechanism remains unknown. Yang et al. identify that AR signaling accelerates the transition from stem cell-like CD8+ T cells to terminally exhausted CD8+ T cells in males, leading to sex-biased antitumor immunity, whereas AR signaling inhibition reprograms CD8+ T cells into a stem cell-like state to potentiate cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: Alcohol and tobacco are the two major established environmental factors associated with squamous cell carcinoma of the esophagus (ESCC). However, the prevalence of these exposures differs substantially between men and women. Moreover, the prevalence of smoking has declined in recent years, whereas per capita consumption of alcohol has remained steady in both sexes. Quantifying the burden of ESCC attributable to these causal factors is necessary to inform potential preventive strategies. Methods: We estimated the population attributable fraction (PAF) of ESCC due to smoking and alcohol, using data from an Australian population based case-control study (305 ESCC cases, 1554 controls). Results: Estimated PAF for ESCC were 49% (95% CI: 38-60) and 32% (95% CI: 25-40) due to smoking and heavy alcohol consumption respectively. More than 75% of the ESCC burden in men could be attributed to smokers with heavy alcohol consumption. The highest burden was among _30 pack years smokers who also consumed alcohol heavily (>17 drinks/week); this differed significantly between men (PAF 36%, 95% CI 29-44) and women (PAF 5%, 95% CI 2-10). Among women only, low intakes of fruit and vegetables accounted for about 9% of the ESCC burden. Conclusion: The burden of ESCC attributable to smoking combined with heavy alcohol consumption is remarkably high in men. In women, the burden of ESCC due to these factors is lower, and poor nutrition may also play a role. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The CAO/ARO/AIO-94 phase-III-trial demonstrated a significant improvement of preoperative chemoradiotherapy (CRT) versus postoperative CRT on local control for UICC stage II/III rectal cancer patients, but no effect on long-term survival. In this add-on evaluation, we investigated the association of gender and age with acute toxicity and outcome. Patients and methods: According to actual treatment analyses, 654 of 799 patients had received pre- (n =406) or postoperative CRT (n =248); in 145 patients postoperative CRT was not applied. Gender, age and clinicopathological parameters were correlated with CRT-associated acute toxicity and survival. Results: The 10-year survival was higher in women than in men, with 72.4% versus 65.6% for time to recurrence (p =0.088) and 62.7% versus 58.4% for overall-survival (OS) (p =0.066), as expected. For patients receiving CRT, women showed higher hematologic (p <0.001) and acute organ toxicity (p <0.001) in the entire cohort as well as in subgroup analyses according to pre- (p =0.016) and postoperative CRT (p <0.001). Lowest OS was seen in patients without acute toxicity (p =0.0271). Multivariate analyses for OS showed that acute organ toxicity (p =0.034) was beneficial while age (p <0.001) was associated with worse OS. Discussion: Female gender is significantly associated with CRT-induced acute toxicity in rectal cancer. Acute toxicity during CRT may be associated with improved long-term outcome. [Copyright &y& Elsevier]

Background Most cancers occur more frequently in men. Numerous explanations for this excess risk have been proposed, yet no study has quantified the degree to which height explains the sex difference even though greater height has been associated with increased risk for many cancers. Methods During the period from 2000 to 2002, 65308 volunteers aged 50 to 76 years were recruited to the Vitamins And Lifestyle (VITAL) study. Cancers of shared anatomic sites (n = 3466) were prospectively identified through 2009 through the Surveillance, Epidemiology, and End Results cancer registry. Age- and race-adjusted hazard ratios (HRs) for the associations between sex and incident cancers were estimated using Cox proportional hazards models, with and without adjustment for height and height squared as measures of body size. Results Men had a 55% increased risk of cancer at shared sites (HR = 1.55; 95% confidence interval [Cl] = 1.45 to 1.66). When height was accounted for, 33.8% (95% Cl = 10.2% to 57.3%) of the excess risk for men was explained by the height differences between sexes. The proportion mediated by height was 90.9%, 57.3%, and 49.6% for kidney, melanoma, and hematologic malignancies, respectively, with little evidence that height mediates the sex difference for gastrointestinal tract, lung, and bladder cancers. For comparison, more than 35 lifestyle and medical risk factors only explained 23.1% of the sex difference in cancer risk at shared sites. Conclusions Height is an important explanatory factor for the excess risk for men for many shared-site cancers. This suggests that some of the excess risk is due to factors associated with height (eg, number of susceptible cells in a specific organ or growth-influencing exposures in childhood). [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Mucinous cystic neoplasm (MCN) and solid pseudopapillary neoplasm (SPN) of the pancreas are uncommon hormone-related pancreatic tumors (HRPTs) with a clear predominance in young women. This trial aims to investigate the possible association between HRPTs development in males and phenotypic and sex hormone alterations. Methods: We performed a retrospective analysis of our database between February 1990 and February 2012. Risk factors for sexual dysfunction were considered exclusion criteria. We investigated secondary sexual characteristics development, sex hormone level and overall sexual dysfunction degree according with the International Index of Erectile Function Questionnaire (IIEF). Results: We initially identified 25 patients [(MCN: n = 16 (64%); SPN: n = 9 (36%)]. At follow-up, 5 patients were lost, 8 resulted dead and 3 were excluded according to exclusion criteria. We finally enrolled 9 patients (MCN: n = 5; SPN: n = 4). Puberty occurred within physiological age for 7 patients, whereas it was delayed in 2 cases. Three patients revealed mild to moderate sexual dysfunction, along with low testosterone level in two cases. One patient presented hormonal alteration with a normal IIEF score. Discussion: In this study, the first in literature with similar aim, hormonal and/or sexual dysfunction was present in 4 out of 9 patients affected by HRPT. The rarity of these lesions makes further trials to be needed for reliable conclusions. [Copyright &y& Elsevier]

Differences in cancer incidences between men and women are often explained by either differences in environmental exposures or by influences of sex hormones. However, there are few studies on intrinsic gender differences in susceptibility to chemical carcinogens. We have analyzed the National Toxicology Program (NTP) database for sex differences in rat responses to chemical carcinogens. We found that the odds that male rat bioassays were assigned a higher level of evidence than female rat bioassays was 1.69 (p < .001). Of 278 carcinogenic chemicals in the database, 201 (72%) exhibited statistical gender differences (p ≤ .05) in at least one nonreproductive organ. One hundred thirty of these 201 chemicals induced gender-specific tumors in male rats and 59 in female rats. Sixty-eight chemicals induced tumors in males but no tumors in females. Less than one third (i.e., 19 chemicals) induced tumors in females but not males. Male-specific tumors included pancreatic and skin tumors, and female-specific tumors included lung tumors. For some tumor sites, these differences in gender susceptibility can be associated with literature data on sex hormone receptor expression. In conclusion, gender-specific tumors were common. The male dominance is in line with recent human data, and the male susceptibility to carcinogens should be further studied. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the association of body mass index (BMI) and physical activity (PA) during adulthood and at the age of 18 years with risk of non-Hodgkin lymphoma (NHL). Methods: We enrolled 950 newly diagnosed NHL patients and 1146 frequency-matched clinic-based controls. Height, weight, and PA (recent adult and at the age of 18 years) were self-reported. Odds ratios (ORs), 95% confidence intervals, and tests for trend were estimated using unconditional logistic regression adjusted for age, gender, and residence. Results: BMI at the age of 18 years was associated with an increased NHL risk (OR, 1.38 for highest vs. lowest quartile; p-trend = .0012), which on stratified analysis was specific to females (OR, 1.90; p-trend = .00025). There was no association of adult BMI with NHL risk. Higher PA in adulthood (OR, 1.03; p-trend = .85) or at the age of 18 years (OR, 0.88; 95% confidence interval, 0.72–1.07) was not associated with risk, but there was an inverse association for adult PA that was specific to females (OR, 0.71; p-trend = .039). Only BMI at the age of 18 years remained significantly associated with NHL risk when modeled together with PA in adulthood or at the age of 18 years. There was little evidence for heterogeneity in these results for the common NHL subtypes. Conclusions: Early adult BMI may be of greatest relevance to NHL risk, particularly in females. [Copyright &y& Elsevier]

Background: Studies of colorectal cancer (CRC) have suggested different mechanisms of carcinogenesis in men and women, young and old patients, right- and left sided tumors, and sporadic and familial tumors. These differences might be reflected in morphology. Methods: CRCs from 1613 patients operated on in 2004-2006 in Sweden were histologically reviewed. Morphology was examined in relation to sex, age groups, location, and family history. Results: Tumors in the right colon were larger, of higher stage, more often poorly differentiated, more mucin-producing, more often had a peritumoral lymphocytic infiltrate and a high level of tumor-infiltrating lymphocytes (TILs), and more seldom had an infiltrating margin than tumors in the left colon and rectum ( p < 0.0001 for most features). Young patients (<60 years) more seldom had multiple tumors but more often had perineural invasion, an infiltrative tumor margin, and high-stage tumors. Three features, TILs, medullary tumors, and invasive tumor margin, were related to sex. Only vascular invasion was related to familiality. Conclusion: Location is the factor that has the most influence on tumor morphology. The results support the idea that different carcinogenic mechanisms may be involved in the right and left colon. Age is the most important determinant for the presence of multiple tumors and is a crucial factor for the aggressiveness of the disease. [ABSTRACT FROM AUTHOR]

Objective. To compare the occurrence of pre-existing and subsequent comorbidity among older cancer patients (⩾ 60 years) with older non-cancer patients. Material and Methods. Each cancer patient (n = 3835, mean age 72) was matched with four non-cancer patients in terms of age, sex, and practice. The occurrence of chronic diseases was assessed cross-sectionally (lifetime prevalence at time of diagnosis) and longitudinally (incidence after diagnosis) for all cancer patients and for breast, prostate, and colorectal cancer patients separately. Cancer and non-cancer patients were compared using logistic and Cox regression analysis. Results. The occurrence of the most common pre-existing and incident chronic diseases was largely similar in cancer and non-cancer patients, except for pre-existing COPD (OR 1.21, 95% CI 1.06-1.37) and subsequent venous thrombosis in the first two years after cancer diagnosis (HR 4.20, 95% CI 2.74-6.44), which were significantly more frequent (P < 0.01) among older cancer compared to noncancer patients. Conclusion. The frequency of multimorbidity in older cancer patients is high. However, apart from COPD and venous thrombosis, the incidence of chronic diseases in older cancer patients is similar compared to non-cancer patients of the same age, sex, and practice. [ABSTRACT FROM AUTHOR]

Purpose: Inhibition of tumor proliferation rate based on bromodeoxyuridine labelling index (BrdUrdLI), S-phase fraction (SPF) and MIB-1 labelling index (MIB-1 LI) as an early rectal cancer response to preoperative radiotherapy (RT).Methods and Materials: A total of 122 patients qualified either for short RT (5 Gy/fraction/5 days) and surgery about 1 week after RT (schedule I) or for short RT and a 4-week interval before surgery (schedule II). Tumor samples were taken twice from each patient: before RT and at the time of surgery. In each sample, the BrdUrdLI, SPF and MIB-1 were calculated. Early tumor response was assessed by a biologist, a pathologist and surgeons.Results: Fifty-six patients were treated according to schedule I and 66 patients according to schedule II. Mean BrdUrdLI, SPF and MIB-1 LI before RT were 8.8%, 21.0% and 53.3%, respectively, and these values did not differ between the two compared groups. After RT, tumors showed statistically significant growth inhibition based on all assessed biological markers. As pretreatment assessed parameter was not predictive for early clinical and pathologic tumor response, prognostic role of the relative value (RV), that is, the ratio of assessed parameter after RT to before RT for each of the assessed markers, was considered. The ratios were calculated separately for fast and slowly proliferating tumors and separately for male and female patients. Fast proliferating tumors were more responsive. Differences with regard to sex were visible only in slowly proliferating tumors. Accelerated cell repopulation (4.8-28%/day) was noticed in female slowly proliferating tumors about 4 weeks after RT. Only for relative MIB-1 LI it was possible to show significant correlation with pathological tumor regression. Lack of such correlation for BrdUrdLI and SPF might reflect accelerated repopulation, particularly in slowly proliferating female tumors.Conclusions: Accelerated repopulation was noticed in slowly proliferating tumors in females about 4 weeks after RT. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The present ecological study analyzed gender differences in the incidences and trends of laryngeal and hypopharyngeal cancers in Spain and compared these with smoking prevalence and alcohol consumption in the period. Methods: Data were evaluated from seven Spanish Population-Based Cancer Registries, selected with a minimum follow-up period of 10years. Information on smoking prevalence and trends were collected from National Health Surveys; for alcohol consumption the Global Alcohol Database was utilized. Trends in the incidences of cancer, smoking and alcohol consumption were analyzed by log-linear joinpoint regression. Results: Analysis of the seven groups of registries revealed a statistically significant reduction in the incidence of laryngeal cancer in men (APC=−4.2) over time and a non-significant increase in women (APC=0.6), with data on prevalence of smoking revealing similar trends. For hypopharyngeal cancer in men an initial increase of 10.6% per year was observed, followed by a reduction of −7.2%; however in women a constant increase of 2.8% per year was observed in the evaluated period. Conclusions: In recent years, the incidence of laryngeal and hypopharyngeal cancers have increased in Spanish women and decreased in Spanish men, narrowing the gap between genders for this neoplasm. The identified trends are probably related to the consumption of tobacco and alcohol; however other risk factors should also be addressed. [Copyright &y& Elsevier]

Abstract: Context: Patients with advanced cancer often experience multiple concurrent symptoms. Few studies have explored symptom clusters (SCs) in this population. Objectives: The aim of the present study was to explore SCs in advanced cancer, evaluate the characteristics associated with various clusters, and determine their relationship to survival. Methods: This study included patients in the palliative care program of the Hospital Universitario La Paz from 2003 to 2005. The Edmonton Symptom Assessment System and a supplement including 13 other symptoms were used to detect symptoms. Principal component analysis was performed to determine symptom relationships and compare SCs with associated parameters. Results: In total, 406 patients were included, 61% men and 39% women. The median age was 66.4 (range 18–95). The most common primaries were gastrointestinal (35%), lung (25%), genitourinary (8%), breast (5%), and head and neck (5%) carcinomas. The following clusters were identified: confusion (cognitive impairment, agitation, urinary incontinence), neuropsychological (anxiety, depression, and insomnia), anorexia-cachexia (anorexia, weight loss, and tiredness), and gastrointestinal (nausea and vomiting). The presence of these SCs was influenced by primary cancer site, gender, age, and performance status. Survival was related to the number of SCs present in a given patient: zero SC, 52 days; one SC, 38 days; two SCs, 23 days; and three to four SCs, 19 days; P <0.001. Conclusion: Different SCs can be identified in patients with advanced cancer. These SCs are influenced by primary cancer site, gender, age, and Eastern Cooperative Oncology Group performance status, and they can have prognostic value. [Copyright &y& Elsevier]

Purpose: Recent reports have shown an increase in frequency of intra-hepatic cholangiocarcinoma (IHC) with a stable or decreased frequency of extra-hepatic cholangiocarcinoma (EHC). However, data on the demographic patterns associated with this change are limited. We analyzed cases of cholangiocarcinoma (CC) with aim to study frequency and demographic patterns over time of IHC and EHC. Methods: Data were collected from MD Anderson Cancer Center Tumor Registry on CC (1978-2007) and stratified on age (<50, 50-59, 60-69, and ≥70 years), gender, ethnicity (Caucasian, African-American, Hispanic, and Other), time (1978-1987, 1988-1997, 1998-2007), and diagnosis (IHC and EHC). Chi-square tests and logistic regression were used for statistics. Results: Of 1,061 CC (445 IHC), proportion of IHC increased from 30% in 1978-1998 to 48% during 1998-2007 ( P < 0.0001). Compared to EHC, IHC occurred more frequently in relatively young (age < 60 years) (21 and 27% vs. 15 and 23% in 0-49 years and 50-59 years, respectively; P = 0.003) and females (48 vs. 42%, P = 0.03). Ethnic distribution was similar. There was significant ( P = 0.019) interaction between age and gender using logistic regression analysis. Conclusions: Increase in frequency of IHC occurred over time and is more frequently observed among females <60 years. These data may have implications in understanding pathogenesis of IHC. [ABSTRACT FROM AUTHOR]

To receive cancer diagnosis brings future-related ambiguity along with it, whereas chemotherapy adds new fears due to side effects. A number of patients use Complementary Alternative Medicine (CAM) to increase the spiritual support, quality of life and survival after cancer diagnose and against symptoms and side effects of cancer therapies. CAM usage rates are increasing in patients who receive conventional treatment whereas many of the health care providers do not have any information about the use of CAM. Is important to take a role health professional' in determining use of alternative therapy in patients. In addition, health professionals the evaluation of CAM, health care system, coordination, information related to the increasing use of CAM, such as determining the user about the cultural and gender differences have important responsibilities. This article has been compiled that is about the alternative therapies used for cancer treatment side effects in order to reflect an overall assessment. [ABSTRACT FROM AUTHOR]

Background: In Italy, some of the highest incidence rates (IRs) of thyroid cancer (TC) worldwide have been reported.Patients and methods: TC cases <85 years of age reported to Italian cancer registries during 1991–2005 were included. Age-standardized IRs were computed for all TC and age–period–cohort effects were estimated for papillary TC.Results: IRs of TC were twofold higher in 2001–2005 than in 1991–1995 (18 and 8 per 100 000 women, 6 and 3 per 100 000 men, respectively). Increases were similar in the two sexes and nearly exclusively due to papillary TC. Increases of papillary TC by birth cohort were found in both sexes and among all age groups between 20 and 79 years. Age–period–cohort models showed a strong period effect in both sexes (rate ratio for 2001–2009 versus 1991–1995 = 2.5 in women and 2.3 in men), although IRs peaked at an earlier age in women (45–49 years) than men (65–69 years).Conclusion: The strength of the period effect in both sexes and the earlier onset in women than men strongly implicated increased medical surveillance in the upward trends of papillary TC incidence in Italy. The consequences of the current intense search for TC on morbidity and possible overtreatment, especially among young women, should be carefully evaluated. [ABSTRACT FROM PUBLISHER]

Abstract: Recent epidemiological studies have disputed whether females are at increased risk of lung cancer compared to males. However, several molecular studies are in support of an increased susceptibility to tobacco smoke carcinogens among females. Our earlier findings suggest that women display higher levels of smoking-induced bulky/hydrophobic DNA adducts which may be related to an increased expression of CYP1A1 in their lungs, compared to men. In this in vitro study, 11 lung adenocarcinoma cell lines, 6 of male and 5 of female origin, were exposed to benzo[a]pyrene, cigarette smoke condensate (CSC), or vehicle control. Subsequent expression analysis of genes in the polycyclic aromatic hydrocarbon bioactivation pathway was conducted with Real-Time RT-PCR. DNA adducts were measured in benzo[a]pyrene-exposed cells by 32P-postlabelling analysis, and CYP1 activity was measured by EROD assay. Analysis of benzo[a]pyrene-DNA adducts showed higher levels of adducts in cell lines from women compared to cell lines from men (p =0.03). The results also revealed significant sex differences in CYP1A1 gene expression, both in untreated cells (p =0.03), and in cells exposed to benzo[a]pyrene (p =0.017) and cigarette smoke condensate (p =0.0043). In CSC-exposed cells, significantly higher levels of CYP1 activity was found in cell lines of female origin (p =0.049). These results are in support of the previously published in vivo data, providing evidence for a higher susceptibility to PAH of women''s lungs. [Copyright &y& Elsevier]

Abstract: Epidemiological studies clearly outline some disparities in cancer onset, progression as well as prognosis and therapeutic response between sexes. In particular, in lung cancer, the leading cause of cancer death, at least in Western countries, a gender disparity appears now to emerge, especially for non-small cell lung cancer (NSCLC). Such a disparity is apparently due to a variety of mechanisms, ranging from genetic and epigenetic differences to gender-specific lifestyle as well as to behavioral causes and, clearly, to sex hormones activity. Here we briefly recapitulate gender differences in terms of risk factors, histopathological features and pathogenetic mechanisms in NSCLC, and hypothesize that a gender-oriented pharmacology could beneficially impact on innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Males with pancreatic cancer have decreased survival compared with females. Interestingly, perioperative blood transfusions have been shown to reduce survival in patients with pancreatic adenocarcinoma. Recent evidence incriminates blood transfusions from female donors as a causative factor in acute lung injury. We therefore hypothesize that male mice with pancreatic cancer will have greater tumor progression than female mice in response to transfusion. Methods: Mice previously inoculated with pancreatic cancer cells received an intravenous injection of acellular plasma collected from single donor erythrocytes from either male or female donors. Control mice received an equal volume of intravenous saline. Necropsy to determine metastasis was performed in female mice at 4 wk status post-transfusion. The male group necessitated sacrifice at 3 wk post-transfusion due to clinical deterioration. Results: Male mice developed more metastatic events than female mice, and this was accentuated when receiving blood from female donors. Male mice experienced weight loss within 2 wk of tail vein injection, and three mice in the male transfused groups died secondary to malignancy. Female mice did not manifest substantial weight loss, and did not die in the study time period. Conclusion: Male mice, compared with female, had significantly more metastatic events following transfusion of plasma from stored erythrocytes in an immunocompetent murine model of pancreatic adenocarcinoma. Moreover, the adverse effect of transfusion was augmented with female donor blood. These data are consistent with clinical outcomes from centers of excellence in treating pancreatic cancer and warrant further investigation. [ABSTRACT FROM AUTHOR]

Background & Aims: Screening recommendations for colorectal cancer (CRC) commonly take family history but no other risk factors into account. We compared and assessed risk factors of colorectal polyps in a large population undergoing screening colonoscopy. Methods: We conducted a population-based cross-sectional study that included 3349 subjects, 55 years or older (mean ages of men and women, 63.6 and 63.4 years, respectively), who underwent colonoscopy for the first time within the nationwide colonoscopy screening program in Germany. We calculated prevalences of colorectal polyps and estimated multivariate prevalence ratios (PRs) and population attributable fractions (PAFs). Results: Overall, 654 subjects had hyperplastic polyps (20%), 675 had non-advanced adenomas (20%), 343 had advanced adenomas (10%), and 40 had CRC (1%). Risk factor prevalences and adjusted PRs were higher for male gender and smoking than for family history of CRC. PAFs for prevalence of non-advanced and advanced neoplasia were highest for male gender (23% and 23%, respectively), followed by smoking (7% and 9%, respectively), and family history of CRC (2% and 4%, respectively). Conclusions: Male gender and smoking have a larger impact on the prevalence of colorectal neoplasia than family history, suggesting an extensive evaluation of additional risk stratification in population-based screening, particularly by sex. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether gender variations in imaging and healthcare access are contributing to observed differences in renal cancer, we examine the initial events in the diagnosis of renal masses in a cohort of patients and correlate it with detailed data on imaging patterns over the same period. Methods: A total of 308 patients diagnosed with a renal mass over 11 years were reviewed. Information on symptoms, imaging, diagnosing physician, demographics, and pathology was gathered. Data on imaging for 1 862 485 patients at our institution over the same period were also collected. The data were analyzed for temporal trends, gender variations, and differences between incidental and nonincidental masses. Results: Females presented with smaller masses (4.8 vs 6.0 cm, P = .0064), and were less likely to have clear cell tumors (58.7% vs 63.4%, P = .049). A total of 66.9% of female and 61.1% of male cases were incidental (not significant). In both males and females, primary care physicians were the most common diagnosing physicians (47.4% and 49.6%, respectively). Gynecologic complaints were an uncommon cause of diagnosis for women (5.3%). Computerized tomography was the most common diagnosing modality for both males and females (69.1% and 63.2%, respectively). Ultrasound as the diagnosing modality did not reach statistical significance between males and females (23.4% and 28.6%, respectively). During the 11- year period, women underwent more imaging studies overall than men (19.7% difference), but the difference was lower when only considering studies that can diagnose renal masses (6.4% difference). Conclusions: Gender variations in imaging rates and presentation for obstetrics/gynecology concerns by females did not lead to a significant difference in incidental diagnosis and do not appear adequate to explain gender differences in renal cancer presentation. [Copyright &y& Elsevier]