Genetic variation in genes interacting with BRCA1/2 and risk of breast cancer in Cypriot population.

Inability to correctly repair DNA damage is known to play a role in the development of breast cancer. Single nucleotide polymorphisms (SNPs) of DNA repair genes have been identified, which modify the DNA repair capacity, which in turn may affect the risk of developing breast cancer. To assess whether alterations in DNA repair genes contribute to breast cancer, we genotyped 62 SNPs in 29 genes in 1,109 Cypriot women with breast cancer and 1,177 age-matched healthy controls. Five SNPs were associated with breast cancer. SNPs rs13312840 and rs769416 in the NBS1 gene were associated with a decrease in breast cancer risk (OR TT vs. TC/CC = 0.58; 95% CI, 0.37-0.92; P = 0.019 and OR GG vs. GT/TT = 0.23, 95% CI 0.06-0.85, P = 0.017, respectively). The variant allele of MRE11A rs556477 was also associated with a reduced risk of developing the disease (OR AA vs. AG/GG = 0.76; 95% CI, 0.64-0.91; P = 0.0022). MUS81 rs545500 and PBOV1 rs6927706 SNPs were associated with an increased risk of developing breast cancer (OR GG vs. GC/CC = 1.21, 95% CI, 1.02-1.45; P = 0.031; OR AA vs. AG/GG = 1.53, 95% CI, 1.07-2.18; P = 0.019, respectively). Finally, haplotype-based tests identified significant associations between specific haplotypes in MRE11A and NBS1 genes and breast cancer risk. Further large-scale studies are needed to confirm these results

Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies

Background Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis. Methods We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria. Results A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence. Conclusion In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility

Body size and obesity during adulthood, and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies.

BACKGROUND: To summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers. METHOD: We conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose-response summary relative risks (RRs). RESULTS: Our findings showed BMI, and BMI in early adulthood (aged 18-21 years) is associated with the risk of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5 kg/m2 increase in BMI were 1.12 [95% confidence interval (CI): 1.05-1.20] for HL, 1.05 (95% CI: 1.03-1.08) for NHL, 1.11 (95% CI: 1.05-1.16) for DLBCL, 1.06 (95% CI: 1.03-1.09) for ML, 1.09 (95% CI: 1.03-1.15) for leukaemia, 1.13 (95% CI: 1.04-1.24) for AML, 1.13 (95% CI: 1.05-1.22) for CML and 1.04 (95% CI: 1.00-1.09) for CLL, and were1.12 (95% CI: 1.05-1.19) for NHL, 1.22 (95% CI: 1.09-1.37) for DLBCL, and 1.19 (95% CI: 1.03-1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM. CONCLUSION: Our results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers.This work was funded by the World Cancer Research Fund Network (grant number 2007/SP01) as part of the Continuous Update Project (http://www.wcrf-uk.org/)

Association between adiposity after diagnosis of prostate cancer and mortality: systematic review and meta-analysis

OBJECTIVE To explore the associations between adiposity indices, assessed at or after a diagnosis of prostate cancer, and mortality. DESIGN Systematic review and meta-analysis. DATA SOURCES PubMed and Embase, from inception to 16 November 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Cohort studies or randomised controlled trials of men with a diagnosis of prostate cancer that investigated the associations between adiposity (body mass index, waist and hip circumference, waist-to-hip ratio, and subcutaneous and visceral adipose tissue) after diagnosis and mortality outcomes. A modified version of the risk of bias for nutrition observational studies tool was used to assess risk of bias. RESULTS 79 studies were identified that investigated adiposity indices after a diagnosis of prostate cancer in relation to mortality. No randomised controlled trials were found. A non-linear dose-response meta-analysis indicated a J shaped association between body mass index and all-cause mortality (33910 men, 11095 deaths, 17 studies). The highest rate of all-cause mortality was found at the lowest and upper range of the distribution: 11-23% higher rate for a body mass index of 17-21and 4-43% higher rate for a body mass index of 30-40. The association between body mass index and mortality specific to prostate cancer was flat until body mass index reached 26- 27, and then increased linearly by 8-66% for a body mass index of 30-40 (33137 men, 2947 deaths, 13 studies), but the 95% confidence intervals were wide. These associations did not differ in most predefined subgroups by study design, number of deaths, anthropometric assessment, follow-up time, geographical location, prostate cancer risk group, and adjustment variables. No associations were found in meta-analyses between 10cm increases in waist circumference and all-cause mortality or mortality specific to prostate cancer, but only three studies were available. The few studies with data on change in weight, waist-to-hip ratio, and subcutaneous and visceral adipose tissue reported conflicting results. CONCLUSIONS This review suggests that patients with prostate cancer might benefit from maintaining a healthy weight and avoiding obesity. Future studies should investigate adiposity across different stages of cancer survivorship and use various parameters for distribution of adipose tissue

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots

Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7–8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry

Gene polymorphisms affecting HDL-cholesterol levels in the normolipidemic population

Summary Background and aim: HDL-cholesterol (HDL-C) is inversely related to the risk of ischemic heart disease. Many genes are reported to affect HDL-C serum levels in both hyperlipidemic and normolipidemic populations, though the data are controversial. We examined the effect of common gene polymorphisms known to interfere with HDL-C metabolism (apolipoprotein E, cholesterol ester transfer protein and apolipoprotein A-IV gene polymorphisms) on HDL-C plasma levels in normolipidemic subjects. Methods and results: The study population consisted of 200 normolipidemic individuals visiting our clinic for a routine check-up. None of the above gene polymorphisms affected HDL-C levels in our population. However, participants carrying the allele E4 of the apolipoprotein (apo) E gene, the allele B1 of the TaqIB polymorphisms in the cholesterol ester transfer protein (CETP) gene and the allele T of the apoA-IV gene (A to T polymorphism at site 347) (nZ28) had statistically significantly lower HDL-C levels compared to those not carrying the above allele combination (0.99G0.33 vs 1.28G0.35 mmol/L, pZ0.04). Conclusion: In this study, we describe a subgroup of normolipidemic individuals with low HDL-C levels due to genetic variability, and we discuss the underlying possible mechanisms involved.

World Cancer Research Fund International: Continuous Update Project—systematic literature review and meta-analysis of observational cohort studies on physical activity, sedentary behavior, adiposity, and weight change and breast cancer risk

Purpose: The purpose of the present study was to systematically review the complex associations between energy balance-related factors and breast cancer risk, for which previous evidence has suggested different associations in the life course of women and by hormone receptor (HR) status of the tumor. Methods: Relevant publications on adulthood physical activity, sedentary behavior, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, and weight change and pre- and postmenopausal breast cancer risk were identified in PubMed up to 30 April 2017. Random-effects meta-analyses were conducted to summarize the relative risks across studies. Results: One hundred and twenty-six observational cohort studies comprising over 22,900 premenopausal and 103,000 postmenopausal breast cancer cases were meta-analyzed. Higher physical activity was inversely associated with both pre- and postmenopausal breast cancers, whereas increased sitting time was positively associated with postmenopausal breast cancer. Although higher early adult BMI (ages 18–30 years) was inversely associated with pre- and postmenopausal breast cancers, adult weight gain and greater body adiposity increased breast cancer risk in postmenopausal women, and the increased risk was evident for HR+ but not HR− breast cancers, and among never but not current users of postmenopausal hormones. The evidence was less consistent in premenopausal women. There were no associations with adult weight gain, inverse associations with adult BMI (study baseline) and hip circumference, and non-significant associations with waist circumference and waist-to-hip ratio that were reverted to positive associations on average in studies accounting for BMI. No significant associations were observed for HR-defined premenopausal breast cancers. Conclusion: Better understanding on the impact of these factors on pre- and postmenopausal breast cancers and their subtypes along the life course is needed

Fatal gunshot trauma of a child: A case from colonial Cyprus

Forensic science has made some significant contributions to the investigation of human rights abuses related to armed conflicts, especially in the last 40 years. Some investigations are aimed at the collection of evidence in order to prosecute those responsible, while others are humanitarian in nature. This paper presents the multidisciplinary effort to recover and identify the remains of a 7-year-old child who was shot by British colonial forces in Cyprus in 1956. An investigation led to the discovery of the burial site, and archaeological methods were used to recover the remains. The anthropological examination provided information about the age of the child, as well as the nature of the skeletal trauma present. DNA results confirmed the identity of the victim, and the remains were released to the surviving family members for burial

Adiposity assessed close to diagnosis and prostate cancer prognosis in the EPIC study

Background: Adiposity has been characterized as a modifiable risk factor for prostate cancer. Its association with outcomes after prostate cancer diagnosis, however, must be better understood, and more evidence is needed to facilitate the development of lifestyle guidance for patients with prostate cancer. Methods: We investigated the associations between adiposity indices close to prostate cancer diagnosis (up to 2 years before or up to 5 years after diagnosis) and mortality in 1968 men of the European Prospective Investigation into Cancer and Nutrition cohort. Men were followed up for a median of 9.5 years. Cox proportional hazards models were adjusted for age and year of diagnosis, disease stage and grade, and smoking history and stratified by country. Results: Each 5-unit increment in prediagnosis or postdiagnosis body mass index combined was associated with a 30% higher rate of all-cause mortality and a 49% higher rate of prostate cancer–specific mortality. Similarly, each 5-unit increment in prediagnosis body mass index was associated with a 35% higher rate of all-cause mortality and a 51% higher rate of prostate cancer–specific mortality. The associations were less strong for postdiagnosis body mass index, with a lower number of men in analyses. Less clear positive associations were shown for waist circumference, hip circumference, and waist to hip ratio, but data were limited. Conclusions: Elevated levels of adiposity close to prostate cancer diagnosis could lead to higher risk of mortality; therefore, men are encouraged to maintain a healthy weight. Additional research is needed to confirm whether excessive adiposity after prostate cancer diagnosis could worsen prognosis