Germline genetic variability in pancreatic cancer risk and prognosis.

Pancreatic cancer (PC), particularly its most common form, pancreatic ductal adenocarcinoma (PDAC), is relatively rare but highly lethal. Knowledge about PC risk factors could in the long term contribute to early diagnosis and mortality reduction. We review the current status of research on germline genetic factors for PC risk. Genome-wide association studies (GWAS) successfully identified common loci convincingly associated with PC risk, an endeavor that is still ongoing. The function of only a handful of risk loci has being thoroughly characterized so far. Secondary analyses of existing GWAS data are being used to discover novel loci. GWAS data have also been used to study additional risk factors with a Mendelian randomization approach. Polygenic/multifactorial risk scores show much larger risks than individual variants, but their use for risk stratification in the population is not warranted yet. At the other end of the spectrum of inherited PC risk factors, rare high-penetrance variants co-segregating with the disease have been observed in familial cancer syndromes that include PC, or in families with multiple recurrence of PC alone. Rare variants predicted to have a deleterious effect on function are studied also with a case-control approach, by resequencing candidate genes or whole-exomes/whole-genomes. Telomere length and mitochondrial DNA copy number are useful additional DNA-based markers of PC susceptibility. The role of common variants in prognosis of PC patients has also been explored, albeit with more limited success than risk. Finally, genetics of pancreatic neuroendocrine tumors (PNET), a rarer and heterogeneous form of PC, is still understudied.

Exploring breast tissue microbial composition and the association with breast cancer risk factors.

BACKGROUND: Microbial dysbiosis has emerged as an important element in the development and progression of various cancers, including breast cancer. However, the microbial composition of the breast from healthy individuals, even relative to risk of developing breast cancer, remains unclear. Here, we performed a comprehensive analysis of the microbiota of the normal breast tissue, which was analyzed in relation to the microbial composition of the tumor and adjacent normal tissue. METHODS: The study cohorts included 403 cancer-free women (who donated normal breast tissue cores) and 76 breast cancer patients (who donated tumor and/or adjacent normal tissue samples). Microbiome profiling was obtained by sequencing the nine hypervariable regions of the 16S rRNA gene (V1V2, V2V3, V3V4, V4V5, V5V7, and V7V9). Transcriptome analysis was also performed on 190 normal breast tissue samples. Breast cancer risk score was assessed using the Tyrer-Cuzick risk model. RESULTS: The V1V2 amplicon sequencing resulted more suitable for the analysis of the normal breast microbiome and identified Lactobacillaceae (Firmicutes phylum), Acetobacterraceae, and Xanthomonadaceae (both Proteobacteria phylum) as the most abundant families in the normal breast. However, Ralstonia (Proteobacteria phylum) was more abundant in both breast tumors and histologically normal tissues adjacent to malignant tumors. We also conducted a correlation analysis between the microbiome and known breast cancer risk factors. Abundances of the bacterial taxa Acetotobacter aceti, Lactobacillus vini, Lactobacillus paracasei, and Xanthonomas sp. were associated with age (p < 0.0001), racial background (p < 0.0001), and parity (p < 0.0001). Finally, transcriptome analysis of normal breast tissues showed an enrichment in metabolism- and immune-related genes in the tissues with abundant Acetotobacter aceti, Lactobacillus vini, Lactobacillus paracasei, and Xanthonomas sp., whereas the presence of Ralstonia in the normal tissue was linked to dysregulation of genes involved in the carbohydrate metabolic pathway. CONCLUSIONS: This study defines the microbial features of normal breast tissue, thus providing a basis to understand cancer-related dysbiosis. Moreover, the findings reveal that lifestyle factors can significantly affect the normal breast microbial composition.

Increased Hazard Risk of First Malignancy in Adults with Undetectable Serum IgE: a Retrospective Cohort Study.

PURPOSE: The clinical relevance of IgE-deficiency is not established. Previous studies have postulated a relationship between absent serum IgE and the incidence of specific malignancies. We sought to examine the relationship between undetectable total serum IgE (< 3 IU/mL) and first malignancy, considering both general all-cause malignancy risk and risk of specific malignancy subtypes in adult subjects. METHODS: Retrospective cohort study at a single center of 39,965 adults aged 18 or older (median age 51, 65.1% female) with at least one serum total IgE measurement from 1998 to 2020. Analytics included chi2 table and logistic regression modeling of the main outcome measures, which include diagnosis of first malignancy and first diagnosis of specific malignancy subtype. RESULTS: Of the entire cohort, 2584 subjects (6.5%) developed a first malignancy and 2516 (6.3%) had an undetectable IgE. Of those with undetectable IgE levels, 8.9% developed a first malignancy versus 6.3% with detectable IgE measurements. After adjusting for risk factors, there was a significant association between undetectable IgE and risk/hazard of first malignancy (relative risk 1.49, 95% confidence interval (CI) 1.27-1.75) (hazard ratio 1.28, 95% CI 1.08-1.52). Results were similar in multiple sensitivity analyses. For type of malignancy developed, undetectable IgE was associated with increased risk of hematologic malignancy (relative risk 2.07, 95% CI 1.29-3.30) and skin malignancy (relative risk 1.52, 95% CI 1.13-2.05). CONCLUSION: Compared to individuals with detectable IgE levels, patients with undetectable total serum IgE had increased risk and hazard of first malignancy in general, and increased risk of hematologic malignancy in particular.

Knowledge of cancer risk factors and risk-reduction in high-income countries.

According to the International Public Opinion Survey on Cancer 2020, on average, nearly 1 in 3 individuals in high-income countries (HIC) did not engage in risk reduction. Meanwhile, only 1 in 4 individuals reported being aware that eating red and processed meat was a cancer risk factor. We explored relations between risk-reduction behavior and self-perceived knowledge of cancer risk factors in HIC using data from the survey. The average effect of knowledge, and interaction effects with country and risk factor were estimated using a linear model fit. The model included main and two-way interaction terms between the proportion of respondents who knew about a specific risk factor, and risk factor and country. The overall significance of knowledge impact and interaction terms was tested using type III tests in ANCOVA. Based on our analysis, we found that knowledge of cancer risk factors was positively associated with risk reduction in HIC. Every unit increase in the proportion of the population knowledgeable about a cancer risk factor, on average across risk factors and HIC, significantly increases the proportion of people engaging in risk reduction by approximately 16.91%. A significant interaction effect was found between knowledge and country, but not between knowledge and risk factor. Using respondents' non-response options to represent lack of risk factor knowledge Japan had the largest percentage of individuals lacking knowledge about risk factors as well as the largest percentage of individuals not engaging in risk reduction.

Factors associated with suspected nonmelanoma skin cancers, dysplastic nevus, and cutaneous melanoma among first-time SpotMe screening program participants during 2009-2010.

BACKGROUND: There have been no studies of the American Academy of Dermatology's SpotMe skin cancer screening program to collectively analyze and determine the factors associated with suspected basal cell carcinoma (BCC), squamous cell carcinoma (SCC), dysplastic nevus (DN), and cutaneous melanoma (CM) diagnoses. OBJECTIVE: Describe the demographics, risk factors, and access to care profiles associated with suspected diagnoses of BCC, SCC, DN, and CM among first-time SpotMe screenees during 2009-2010. METHODS: We conducted a cross-sectional analysis of data from the SpotMe skin cancer screenings conducted in 2009 and 2010. We performed multivariable logistic regression analysis for each diagnosis, incorporating standard demographic, access to care, and risk factor variables in the models. RESULTS: Men, those without a regular dermatologist, persons reporting recently changing moles, and those with a personal history of melanoma were at increased risk for each of the suspected diagnoses analyzed. Uninsured persons were at increased risk for suspected malignancies (BCC, SCC, and CM). LIMITATIONS: Lack of histologic confirmation for diagnoses and cross-sectional design. CONCLUSION: Among first-time SpotMe participants, suspected diagnoses of BCC, SCC, DN, and CM shared several associated factors, which may be considered when planning outreach and screening for populations at risk for skin cancer.

Risk of colorectal cancer in patients with appendicitis over the age of 40 years.

AIM: Acute appendicitis in late adulthood is hypothesized to be associated with an increased risk of colorectal cancer (CRC). This study aimed to establish whether patients over the age of 40 years presenting with appendicitis had an increased risk of being diagnosed with CRC over the subsequent 3 years. METHOD: This is a retrospective review of patients aged 40 years and over presenting to Canterbury District Health Board with appendicitis from January 2010 to December 2015. Clinical details were obtained for these patients and cross-referenced with the New Zealand Cancer Registry for the 3 years following diagnosis. The incidence ratio rate (IRR) and standardized incidence ratio (SIR) were calculated by establishing the incidence of CRC in this cohort and comparing it with the Canterbury population data. RESULTS: A total of 1099 patients met the inclusion criteria. The majority (75%) underwent CT as part of their initial work-up. The rate of colonoscopy increased with age from around 10% between 40 and 49 years to 27% for those 70 years and over. Eleven cases of CRC were identified, resulting in an IRR 2.35 (95% CI 1.17-4.21). The SIR for this population was 3.28 (95% CI 1.82-5.92). CONCLUSION: The rate of CRC is significantly increased compared with the background population in this cohort. The results of this study support luminal investigation of adults aged 40 years and over who present with acute appendicitis as CT alone was insufficient to detect the pathology.

Risk factors and early prevention of skin cancer in rural older outdoor workers: A scoping review.

Skin cancer risk increases with age and prolonged exposure to ultraviolet radiation (UVR), particularly in rural geographical locations and for individuals with light skin complexions. However, the impact of UVR-induced skin cancer risk and sun-protective behaviors in rural older populations working outdoors has yet to be explored. A scoping review was conducted to fill this gap, with 12 articles meeting the inclusion criteria of aged 50 years and older among rural outdoor workers. Skin cancer risk factors, prevention strategies, and barriers to sun-protective behaviors were summarized for each study. The scoping review addressed some key differences in age-related effects of UVR among rural older outdoor workers compared to studies among adults in general. Findings have policy and research implications that highlight the need to design feasible preventive strategies to reduce rural disparities in cancer care and enhance access to preventive services for this high-risk population.

Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women's Health Study: a case-case analysis.

BACKGROUND: Terminal duct lobular units (TDLUs) are the structures in the breast that give rise to most breast cancers. Previous work has shown that TDLU involution is inversely associated with TDLU metrics, such as TDLU count/100mm2, TDLU span (µm), and number of acini/TDLU, and that these metrics may be elevated in the normal breast tissue of women diagnosed with triple-negative (TN) compared with luminal A breast tumors. It is unknown whether this relationship exists in Black women, who have the highest incidence of TN breast cancer and the highest overall breast cancer mortality rate. We examined relationships between TDLU metrics and breast cancer molecular subtype among breast cancer cases in the Black Women's Health Study (BWHS). METHODS: We assessed quantitative TDLU metrics (TDLU count/100mm2, TDLU span (µm), and number of acini/TDLU) in digitized 247 hematoxylin and eosin-stained adjacent normal tissue sections from 223 BWHS breast cancer cases, including 65 triple negative (TN) cancers (estrogen receptor (ER) negative, progesterone receptor (PR) negative, human epidermal growth factor-2 (HER2) negative) and 158 luminal A cancers (ER positive, HER2 negative). We evaluated associations of least square mean TDLU metrics adjusted for age and body mass index (BMI) with patient and clinical characteristics. In logistic regression models, we evaluated associations between TDLU metrics and breast cancer subtype, adjusting for age, BMI, and tumor size. RESULTS: Older age and higher BMI were associated with lower TDLU metrics and larger tumor size and lymph node invasion with higher TDLU metrics. The odds of TN compared with luminal A breast cancer increased with increasing tertiles of TDLU metrics, with odds ratios (95% confidence intervals) for tertile 3 versus tertile 1 of 2.18 (0.99, 4.79), 2.77 (1.07, 7.16), and 1.77 (0.79, 3.98) for TDLU count, TDLU span, and acini count/TDLU, respectively. CONCLUSION: Associations of TDLU metrics with breast cancer subtypes in the BWHS are consistent with previous studies of White and Asian women, demonstrating reduced TDLU involution in TN compared with luminal A breast cancers. Further investigation is needed to understand the factors that influence TDLU involution and the mechanisms that mediate TDLU involution and breast cancer subtype.

Studying the association between breast cancer and renal cell carcinoma.

PURPOSE: There are case reports of patients with both primary breast cancer (BC) and renal cell carcinoma (RCC). We explore the association between these two malignancies using SEER population data and our institutional records. METHODS: We studied the association between BC and RCC in the 2000-2016 Surveillance, Epidemiology, and End Results (SEER) database. We then reviewed our hospital records of patients with both BC and RCC and collected information including personal and family history of cancers, genetic testing, and patient outcomes. RESULTS: Of the 813,477 females diagnosed with BC in the SEER database, 1914 later developed RCC. The risk of developing RCC was significantly increased within the first 6 months, 7-12 months, and 1-5 years following BC diagnosis with standardized incidence ratios (SIRs) of 5.08 (95% CI 4.62-5.57), 2.09 (95% CI 1.8-2.42), and 1.15 (95% CI 1.06-1.24), respectively. Of 56,200 females with RCC, 1087 later developed BC. The risk of developing BC following RCC was elevated within the first 6 months (SIR of 1.45 [95% CI 1.20-1.73]). For our hospital patients, 437 had both BC and RCC. 427 (97.71%) were female, and 358 (81.92%) were white, and breast cancer was diagnosed before RCC in 246 (56.3%) patients. There were 15 germline mutations in those with genetic testing. CONCLUSION: Our findings suggest that BC patients are at higher risk of developing RCC and vice versa. BC tended to precede RCC, and patients frequently had personal histories of other malignancies and a family history of cancer, particularly, BC.

Sugars measured enzymatically in a fasting overnight urine sample are not sensitive biomarkers of dietary added sugar intake in postmenopausal women.

BACKGROUND: Restricting dietary sugar is a leading recommendation, but limited biomarkers assessing intake exist. Although 24-h urinary sucrose (U-Suc) and urinary fructose (U-Fruc) excretion has been used with mixed success, collection is burdensome. AIM: This study aimed to test the sensitivity of an enzymatic assay of U-Suc and U-Fruc to detect changing added sugar intake using low-burden overnight urine samples in 30 postmenopausal women. METHODS: Women consumed usual dietary intake during day 1 and usual intake plus a sugar sweetened beverage during day 2. Weighed, photographed food records assessed intake. Enzymatic assay measured U-Suc and U-Fruc from fasting overnight samples; liquid chromatography mass spectrometry (LC-MS) validated U-Suc findings. RESULTS: Dietary added sugars increased significantly during day 2 (p < 0.001), but urinary sugars were not significantly increased. Enzymatic assay detected urinary sugars in 75% (U-Suc) and 35% (U-Fruc) of samples. Dietary sucrose was not associated with U-Suc, however dietary fructose was significantly associated with U-Fruc [ß = 0.031; p < 0.05] among women with detectable urinary sugars. Participants with detectable U-Fruc consumed more energy from added sugars [12.6% kcal day 1; 21.5% kcal day 2] than participants with undetectable U-Fruc [9.3% kcal day 1; 17.4% kcal day 2], p < 0.05. Using LC-MS, U-Suc predicted sucrose and added sugar intake [ß = 0.017, ß = 0.013 respectively; both p < 0.05]. CONCLUSIONS: Urinary sugars measured enzymatically from overnight urine samples were not sensitive biomarkers of changing added sugar intake in postmenopausal women. However, urinary fructose measured by enzymatic assay or LC-MS may differentiate low versus high added sugar consumers.

Clinical and seminal parameters associated with testicular microlithiasis and its severity in males from infertile couples.

STUDY QUESTION: Is there an association of testicular microlithiasis (TM) and its severity with testicular dysfunction in men from infertile couples? SUMMARY ANSWER: The presence of ≥5 testis microcalcifications per sonogram at the scrotal ultrasonography (US) of infertile males was associated with a more severe testicular dysfunction as compared to males with limited, or without, TM. WHAT IS KNOWN ALREADY: TM, representing an incidental finding in the scrotal US, is associated with male infertility and a higher risk for testicular cancer as compared to that in infertile males without TM. Still, there are unresolved questions on the relation between TM severity and testicular dysfunction in infertile men, as well as on the identification of risk factors for TM. STUDY DESIGN, SIZE, DURATION: This study was an observational, retrospective, case-control investigation involving males who underwent clinical evaluation, measurement of reproductive hormones, seminal analysis and scrotal US as part of diagnostic work-up for couple infertility at an andrology clinic, between January 2004 and December 2018. One hundred patients, out of the 2112 scored men, were found to have TM during the US evaluation. One hundred male partners from 100 infertile couples without TM, comprising the control group, were selected through a matched analysis by age and date of evaluation to reduce the confounding effect of both age and technique variability all along the long period of observation. PARTICIPANTS/MATERIALS, SETTING, METHODS: TM was defined as limited TM (LTM) or classical TM (CTM), when the maximum number of hyperecogenic spots per sonogram was <5 or ≥5, respectively. CTM, LTM and control groups were compared for clinical variables, serum levels of FSH, LH, and total testosterone, as well for semen parameters and scrotal US features. MAIN RESULTS AND THE ROLE OF CHANCE: After the exclusion of cases with testicular nodules to eliminate the possible confounding effect of testis cancer on testicular dysfunction, cases with CTM showed a lower mean testis volume (P = 0.03) and a lower sperm concentration (P = 0.03) as compared to the other two groups. A higher FSH level was observed in the CTM group compared to the LTM group (P = 0.02) and in controls (P = 0.009). The multiple logistic regression analysis showed that only a smaller testicle volume exhibited an independent significant association with a higher odds of detecting CTM (odds ratio = 0.84, 95% CI: 0.75-0.94; P = 0.02). No significant differences were observed between groups in the prevalence of risk factors for testicular cancer, or in the prevalence of conditions associated with TM. LIMITATIONS, REASONS FOR CAUTION: The retrospective design of the study did not allow conclusions to be drawn about the possible underlying links in the associations of TM with defective spermatogenesis. WIDER IMPLICATIONS OF THE FINDINGS: Males from infertile couples who exhibit a reduced testicular volume should undergo scrotal US, independent of sperm parameters, to exclude CTM and, eventually, testis cancer, although the association of CTM and current or future testis cancer risk is not yet clear. Evidence is provided here demonstrating that the presence of LTM has no clinical relevance in males from infertile couples. STUDY FUNDING/COMPETING INTEREST(S): Investigation was funded by Ministero dell'Università e della Ricerca, PRIN 2018, Italy. The authors have not declared any competing interests. TRIAL REGISTRATION NUMBER: N/A.

Knowledge about risk factors for cancer and cancer risk behavior among patients with severe mental illness.

OBJECTIVE: To examine knowledge about, perception of and current risk factors for cancer, among patients with severe mental illness (SMI) and to compare these variables with patients without SMI. METHODS: A series of patients affected by SMI (i.e., schizophrenia spectrum disorders, bipolar disorders and severe personality disorders) and a matched (gender, age) control group of primary care attenders were assessed, by using an ad hoc semi-structured interview and a short true/false 17-item questionnaire, about family history of cancer, cancer risk-related lifestyles, personal perception and knowledge of risk for cancer. RESULTS: Patients with SMI (n = 185, mainly schizophrenia spectrum disorders, 48%, and mood disorders, 33%) significantly differed from primary care attenders (n = 173) for: lower participation to occult stool blood screening test, Pap smear test and mammography; higher prevalence of current and past smoking habits; lower awareness towards their own physical symptoms and their perception of risks for cancer; lower physical exercise practicing; lower knowledge about risk factors for cancer (e.g. familiarity for cancer, smoke-habits, breast and uterine cancer). CONCLUSIONS: Patients suffering from SMI had higher at-risk behavior for cancer and showed fewer concerns and less knowledge about risk for cancer than primary care attendees. These findings can guide to implement screening for cancer (e.g., Pap test, blood) and to design evidence-based interventions to reduce cancer risk (e.g., educational and behavioral change for smoking cessation, dietary habits) among patients with SMI.

Breast cancer awareness among pharmacy and physiotherapy students of medical university Nawabshah.

OBJECTIVE: To evaluate the knowledge and awareness of students at a medical university regarding possible risk factors and screening modalities of breast cancer. METHODS: The cross-sectional study was conducted from January to April 2019 at the People's University of Medical and Health Sciences for Women, Nawabshah, Pakistan, and comprised young female students from first year to final year at the Institute of Pharmaceutical Sciences and the Institute of Physiotherapy and Rehabilitation Sciences of the university. Data was collected using a predesigned questionnaire, and was analysed using SPSS 21. RESULTS: Of the 450 students approached, 375(84%) completed the questionnaire. The mean age of the participants was 21.06±1.164 years (range: 18-26 years). Overall, 225(60%) students said contraceptive pills could increase the risk of breast cancer, 267(71.2%) agreed that breast-feeding could reduce cancer risk, while 361 (96.27%) students had good mammography and clinical breast examination knowledge. Also, 308(82.13%) respondents knew about breast self-examination, but were not aware of its procedure. CONCLUSIONS: Majority of the subjects had knowledge and awareness about breast cancer, its risk factors, diagnostic parameters and possible treatment options, but they did not have knowledge regarding the procedures of breast self-examination.

Demographic variation and risk factors regarding breast cancer among females in Southern Punjab, Pakistan.

OBJECTIVE: To explore epidemiology, clinical profiles and contribution of reproductive and non-reproductive risk factors in breast cancer development. METHODS: The case-control study was conducted from October 2017 to March 2018 at Quaid-i-Azam University, Islamabad, Pakistan, and comprised breast cancer patients and age-matched controls recruited from the Bahawalpur Institute of Nuclear Medicine and Oncology, and the Bahawal Victoria Hospital, Bahawalpur. Socio-demographic data, family history of cancer, reproductive health and lifestyle factors were recorded using a structured questionnaire. Data was analysed using SPSS 21 and Stata/IC 14.1. RESULTS: Of the 326 women, 163(50%) each were cases and controls. The mean age for both the groups was identical at 46.04±10.62 years. Positive family history and hypertension were significantly linked to increased breast cancer risk (p<0.05), while intense physical activity, increased anthropometric measurements and breastfeeding per child in months were inversely associated with the risk (p<0.05). CONCLUSIONS: Established risk factors for breast cancer were reaffirmed.

Effectiveness of educational intervention in raising knowledge regarding breast cancer among female nurses.

OBJECTIVE: To assess the effect of nursing educational session on nurses' knowledge level related to breast cancer. METHODS: The quasi-experimental study was conducted at the Dow University of Health Sciences, and the Dr. Ruth Pfau Civil Hospital, Karachi, from January to July 2018, and comprised nurses from two tertiary care hospitals. A single educational session lasting 90-120-minute was conducted for all the subjects. Knowledge level was tested at baseline and post-intervention using the Comprehensive Breast Cancer Knowledge Test questionnaire. Data was analysed using SPSS 20. RESULTS: There were 131 nurses with a mean age of 31.05±6.23 years (range: 18-47 years). Overall, 53(40.5%) subjects had General Nursing Diploma; 92(70.2%) were married; 108(82.4%) had no history of breast cancer, 47(35.9%) had 1-4 years of working experience; and 106(80.9%) had completed their graduation from public-sector institutions. The improvement post-intervention was significant in all the three components of knowledge (p<0.05). CONCLUSIONS: Nursing educational session was found to have increased nurses' knowledge related to breast cancer.

The impact of selected risk factors among breast cancer molecular subtypes: a case-only study.

PURPOSE: Breast cancer (BC) risk factors have been differentially associated with BC subtypes, but quantification is still undefined. Therefore, we compared selected risk factors with BC subtypes, using a case-case approach. METHODS: We retrieved 1321 invasive female BCs from the Piedmont Cancer Registry. Through record linkage of clinical records, we obtained data on estrogen (Er) and progesterone (Pr) receptors, Ki67 and HER2+ status, BC family history, breast imaging reporting and data system (BI-RADS) density, reproductive risk factors and education. We defined BC subtypes as follows : luminal A (Er+ and/or Pr+ , HER2- , low Ki67), luminal BH- (Er+ and/or Pr + , HER2- , Ki67 high), luminal BH+ (Er+ and/or Pr + , HER2+), HER2+ (Er - , Pr - , HER2+), ) and triple negative (Er - , Pr - , HER2-). Using a multinomial regression model, we estimated the odds ratios (ORs) for selected BC risk factors considering luminal A as reference. RESULTS: For triple negative, the OR for BC family history was 1.83 (95% confidence interval (CI) 1.13-2.97). Compared to BI-RADS 1, for triple negative, the OR for BI-RADS 2 was 0.56 (95% CI 0.27-1.14) and for BI-RADS 3-4 was 0.37 (95% CI 0.15-0.88); for luminal BH +, the OR for BI-RADS 2 was 2.36 (95% CI 1.08-5.11). For triple negative, the OR for high education was 1.78 (95% CI 1.03-3.07), and for late menarche, the OR was 1.69 (95% CI 1.02-2.81). For luminal BH + , the OR for parous women was 0.56 (95% CI 0.34-0.92). CONCLUSIONS: This study supported BC etiologic heterogeneity across subtypes, particularly for triple negative.

Breast cancer risk factors and their effects on survival: a Mendelian randomisation study.

BACKGROUND: Observational studies have investigated the association of risk factors with breast cancer prognosis. However, the results have been conflicting and it has been challenging to establish causality due to potential residual confounding. Using a Mendelian randomisation (MR) approach, we aimed to examine the potential causal association between breast cancer-specific survival and nine established risk factors for breast cancer: alcohol consumption, body mass index, height, physical activity, mammographic density, age at menarche or menopause, smoking, and type 2 diabetes mellitus (T2DM). METHODS: We conducted a two-sample MR analysis on data from the Breast Cancer Association Consortium (BCAC) and risk factor summary estimates from the GWAS Catalog. The BCAC data included 86,627 female patients of European ancestry with 7054 breast cancer-specific deaths during 15 years of follow-up. Of these, 59,378 were estrogen receptor (ER)-positive and 13,692 were ER-negative breast cancer patients. For the significant association, we used sensitivity analyses and a multivariable MR model. All risk factor associations were also examined in a model adjusted by other prognostic factors. RESULTS: Increased genetic liability to T2DM was significantly associated with worse breast cancer-specific survival (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.03-1.17, P value [P] = 0.003). There were no significant associations after multiple testing correction for any of the risk factors in the ER-status subtypes. For the reported significant association with T2DM, the sensitivity analyses did not show evidence for violation of the MR assumptions nor that the association was due to increased BMI. The association remained significant when adjusting by other prognostic factors. CONCLUSIONS: This extensive MR analysis suggests that T2DM may be causally associated with worse breast cancer-specific survival and therefore that treating T2DM may improve prognosis.

Silica and asbestos exposure at work and the risk of bladder cancer in Canadian men: a population-based case-control study.

BACKGROUND: Silica and asbestos are recognized lung carcinogens. However, their role in carcinogenesis at other organs is less clear. Clearance of inhaled silica particles and asbestos fibers from the lungs may lead to translocation to sites such as the bladder where they may initiate carcinogenesis. We used data from a Canadian population-based case-control study to evaluate the associations between these workplace exposures and bladder cancer. METHODS: Data from a population-based case-control study were used to characterize associations between workplace exposure to silica and asbestos and bladder cancer among men. Bladder cancer cases (N = 658) and age-frequency matched controls (N = 1360) were recruited within the National Enhanced Cancer Surveillance System from eight Canadian provinces (1994-97). Exposure concentration, frequency and reliability for silica and asbestos were assigned to each job, based on lifetime occupational histories, using a combination of job-exposure profiles and expert review. Exposure was modeled as ever/never, highest attained concentration, duration (years), highest attained frequency (% worktime) and cumulative exposure. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated using adjusted logistic regression. RESULTS: A modest (approximately 20%) increase in bladder cancer risk was found for ever having been exposed to silica, highest attained concentration and frequency of exposure but this increase was not statistically significant. Relative to unexposed, the odds of bladder cancer were 1.41 (95%CI: 1.01-1.98) times higher among men exposed to silica at work for ≥27 years. For asbestos, relative to unexposed, an increased risk of bladder cancer was observed for those first exposed ≥20 years ago (OR:2.04, 95%CI:1.25-3.34), those with a frequency of exposure of 5-30% of worktime (OR:1.45, 95%CI:1.06-1.98), and for those with < 10 years of exposure at low concentrations (OR:1.75, 95%CI:1.10-2.77) and the lower tertile of cumulative exposure (OR:1.69, 95%CI:1.07-2.65). However, no clear exposure-response relationships emerged. CONCLUSIONS: Our results indicate a slight increase in risk of bladder cancer with exposure to silica and asbestos, suggesting that the effects of these agents are broader than currently recognized. The findings from this study inform evidence-based action to enhance cancer prevention efforts, particularly for workers in industries with regular exposure.

Nomogram to predict the risk and survival of synchronous bone metastasis in colorectal cancer: a population-based real-world analysis.

PURPOSE: Bone metastasis (BM) can obviously affect the quality of life of patients in colorectal cancer (CRC), and the whole management of patients with BM would be attractive in current clinical practice. METHODS: A total of 52,859 patients during 2010-2015 were collected from Surveillance, Epidemiology, and End Results (SEER) database. After propensity score matching (PSM), cancer-specific survival (CCS) and overall survival (OS) with BM were adopted to assess survival probability difference. Logistic regression was used to identify risk factors for BM; COX proportion hazard regression was applied to explore prognosticators for OS in patients with BM. Subsequently, nomograms were constructed and receiver operating curves (ROCs) were used to confirm the validation of nomogram. RESULTS: Three hundred and forty-two (0.65%) patients were diagnosed with synchronous BM. After PSM, 16 variables were balanced. Tumor site, histology, grade, T stage, N stage, CEA, radiochemotherapy, surgery, and liver/lung/brain metastases were associated with BM, and histology, grade, T stage, N stage, CEA, chemotherapy, surgery, and liver/lung metastases were prognosticators for BM survival. Nomograms were applied and the ROC curve proved the predictive effects. CONCLUSION: CRC patients with BM have worse real-world survival. Nomogram can predict incidence of BM in CRC patients and survival among patients with BM.

Knowledge level of cancer symptoms and risk factors in the Gaza Strip: a cross-sectional study.

BACKGROUND: In low-income settings, cancer is often diagnosed in advanced stages due to late presentation. Good public awareness of cancer signs and symptoms has a positive impact on the time patients take before they present to healthcare professionals. Therefore, this study examined public knowledge of cancer signs and symptoms as well as risk factors in Gaza. METHODS: This was a cross-sectional study. Participants were recruited from adult visitors (≥18 years) to governmental hospitals covering all five governorates of Gaza, and adolescent students (15 to 17 years) from 10 high schools in corresponding locations. An Arabic version of the Cancer Awareness Measure (CAM) was completed in a face-to-face interview. It described demographic data and knowledge of: cancer prevalence, age-related risk, signs and symptoms as well as risk factors both in recall and recognition questions. RESULTS: Of 3033 participants invited, 2886 completed the CAM (response rate = 95.2%). Adult mean age ± standard deviation was 33.7 ± 11.7 years and that of adolescents was 16.3 ± 0.8 years. Half of the participants (n = 1457, 50.5%) were adolescent (781 females; 53.6%) and 1429 (49.5%) were adult (702 females; 49.1%). About two thirds (n = 1885) thought about cancer as unrelated to age. Only 196 participants (6.8%) identified colorectal cancer as the most common cancer among men. Awareness of cancer signs/symptoms was poor to fair, where 'lump' was most commonly recognized (n = 2227, 77.2%) and 'change of bowel habit' the least (n = 670, 23.2%). Only 217 participants (7.5%) had a good level of recognizing risk factors with 'smoking' being the most identified and 'eating less than five portions of fruits and vegetables a day' the least. There was a higher likelihood for adults to identify most cancer signs/symptoms and risk factors than adolescents, except for recalling 'unexplained pain', 'persistent cough/hoarseness', 'non-healing ulcer', 'smoking', and 'eating less than five portions of fruits and vegetables a day'. CONCLUSION: Public awareness of cancer signs/symptoms and risk factors needs to improve to facilitate early presentation and diagnosis in Gaza. Combining the delivery of public campaigns with tailored education to population groups, including the youth, may increase their knowledge and maintain its impact.