Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR. RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) ß, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk. CONCLUSIONS: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.

Risk factors for melanoma by anatomical site: an evaluation of aetiological heterogeneity.

BACKGROUND: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. OBJECTIVES: We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. METHODS: We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. RESULTS: When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. CONCLUSIONS: We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.

Robust image hashing using ring partition-PGNMF and local features.

BACKGROUND: Image authentication is one of the challenging research areas in the multimedia technology due to the availability of image editing tools. Image hash may be used for image authentication which should be invariant to perceptually similar image and sensitive to content changes. The challenging issue in image hashing is to design a system which simultaneously provides rotation robustness, desirable discrimination, sensitivity and localization of forged area with minimum hash length. METHODS: In this paper, a perceptually robust image hashing technique based on global and local features has been proposed. The Global feature was extracted using ring partition and projected gradient nonnegative matrix factorization (PGNMF). The ring partitioning technique converts a square image into a secondary image that makes the system rotation invariant. The PGNMF which is usually faster than the other NMFs has been used to reduce the dimension of the secondary image to generate the shorter hash sequence. The local features extracted from the salient regions of the image help to localize the forged region in the maliciously manipulated images. The image hashing techniques that use only global features are limited in discrimination. RESULTS: The experimental results reveal that the proposed image hashing method based on global and local features provides better discrimination capability. The proposed hashing method is tested on large image sets collected from the different standard database. It is observed from the experimental results that the proposed system is robust to content-preserving operations and is capable of localizing the counterfeit area. CONCLUSIONS: The combination of global and local features is robust against the content-preserving operations, which has a desirable discriminative capability. The proposed system may be used in image authentication, forensic evidence, and image retrieval, etc.

Human papillomavirus testing for suspected cervical cancer patients from Southern Assam by fast-PCR.

World-wide epidemiological studies have shown that cancer of the uterine cervix is the second most common malignant disease in women. Virtually every cervical cancer (99.7%) is HPV-positive, indicating that the presence of HPV is an obligatory element in their development. The present study was conducted by Fast-PCR (within 15 min.) based diagnosis of HPV 16 and HPV 18 infection amongst patients of suspected cervical cancer, confirmed by cytological methods. Twelve women, out of a total of fifty studied cases who had positive cervical pap smears (24%) were found to be positive for HPV 16/HPV 18 infection when PCR based technique was applied. The results indicate, perhaps, a greater specificity of PCR based diagnosis, or presence of other HPV subtypes as etiological factors in the present study group confined to Southern Assam.

Assessment of myocardial perfusion with contrast echocardiography at rest and with stress: an emerging technology.

Over the past 20 years, there has been considerable progress in the field of myocardial contrast echocardiography (MCE). What began as a modality limited to selected cardiac catherization laboratories may soon become a rapid and accurate bedside tool for assessing myocardial perfusion. Because MCE via intravenous contrast injection can be performed at the bedside and avoids the use of radiation exposure, it offers multiple potential clinical applications, including assessment of reperfusion after fibrinolytic therapy, postinfarction risk area, and myocardial viability. The addition of perfusion data to wall motion may augment the results of stress echocardiography. This report describes the technologic advances in contrast agents and related imaging technologies that enable myocardial perfusion to be assessed by echocardiography. In addition, the latest clinical studies of myocardial perfusion by MCE are presented.