The genetic and environmental components in 15 common cancers were estimated using the nationwide Swedish Family-Cancer Database. Tetrachoric correlations were used to describe similarity in cancer liability among family members. Structural equation modeling was used to derive estimates of the importance of genetic and environmental effects. Statistically significant estimates of proportion of cancer susceptibility, accounted for by genetic effects, were obtained for all studied cancers except for leukemia. The estimate was highest in thyroid cancer (53%), followed by tumors at endocrine glands (28%), testis (25%), breast (25%), cervix (22%), melanoma (21%), colon (13%), nervous system (12%), rectum (12%), non-Hodgkin lymphoma (10%), lung (8%), kidney (8%), urinary bladder (7%), stomach (1%) and leukemia (1%). The estimates of shared environmental effects ranged from 0% (cervix) to 15% (stomach). The childhood shared environmental effects were most important in testicular cancer (17%), stomach cancer (13%) and cervix in situ (13%). Our results indicate that environment has a principal causative role in cancer at all studied sites except for thyroid. The relatively large effect of heritability in cancer at some sites, on the other hand, indicates that even though susceptibility genes have been described at many cancer sites, they are likely to explain only part of the genetic effects.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.10332

Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database

When in a patient more than one tumour in the same or a different organ is diagnosed, multiple primary tumours may be present. For epidemiological studies, different definitions of multiple primaries are used with the two main definitions coming from the project Surveillance Epidemiology and End Results and the International Association of Cancer Registries and International Agency for Research on Cancer. The differences in the two definitions have to be taken into consideration when reports on multiple primaries are analysed. In this review, the literature on multiple primaries is reviewed and summarised. Overall, the frequency of multiple primaries is reported in the range of 2-17%. Aetiological factors that may predispose patients to multiple primaries can be grouped into host related, lifestyle factors and environmental influences. Some of the most common cancer predisposition syndromes based on a clinical presentation are discussed and the relevant genetic evaluation and testing are characterised. Importantly, from a clinical standpoint, clinical situations when multiple primaries should be suspected and ruled out in a patient are discussed. Furthermore, general principles and possible treatment strategies for patients with synchronous and metachronous multiple primary tumours are highlighted.

Multiple primary tumours: challenges and approaches, a review.

Cancer of the distal stomach, both of the intestinal and diffuse type, is strongly associated with Helicobacter pylori colonization. This bacterium causes chronic active inflammation of the gastric mucosa in the majority of colonized subjects. In a considerable number of them, this will eventually lead to a loss of gastric glands, and thus the establishment of atrophic gastritis, which is associated with the development of intestinal metaplasia and dysplasia. Development of atrophy and metaplasia of the gastric mucosa are thus strongly associated with H. pylori infection, instead of a direct and inevitable consequence of ageing. Approximately 40–50% of infected subjects develop these conditions, but they are rare in non-infected subjects.



The presence of these consecutive disorders leads to a 5–90-fold increased risk for cancer of the distal stomach, in particular of the intestinal type. This sequence explains the increased risk for gastric cancer in H. pylori-infected subjects, as has been shown in various cross-sectional and longitudinal studies. In a combined analysis of three longitudinal studies, a significant trend was observed towards an increased odds ratio with longer intervals between (retrospective) serological diagnosis of H. pylori infection and observation of gastric cancer, this risk being more than eight-fold increased if the interval had been at least 15 years. This is thought to reflect development of atrophic gastritis and intestinal metaplasia with loss of H. pylori colonization in the years prior to development of cancer. Atrophic gastritis and gastric cancer thus appear closely associated with the presence of H. pylori, yet not all infected subjects will eventually develop atrophy and only a small minority develop gastric cancer. Factors that influence the risks for atrophy and cancer in the presence of infection may be related to the time that infection occurred and to characteristics of the bacterial strain and the host.



Evidence for the role of these factors is now increasing. Recognition of the causal role of H. pylori in the induction of gastric cancer theoretically presents tools for cancer prevention. The efficacy of screening and bacterial eradication for prevention of distal gastric cancer is being studied in a number of large-scale intervention studies in different populations. It is hoped that these studies will also provide answers to the potential preventive role of H. pylori colonization in the development of gastro-oesophageal reflux disease and associated conditions, in particular development of cancer of the proximal stomach.



Infection with H. pylori plays an important role in the aetiology of atrophic gastritis and gastric cancer. Studies suggest an eight-fold increased risk for both conditions in the presence of infection. Factors that influence the risk for both conditions in the presence of infection are the age at which infection occurred and the presence of cagA as a marker for more pathogenetic H. pylori strains. The efficacy and side-effects of intervention for the prevention of distal gastric cancer has yet to be established.

Review article: exploring the link between Helicobacter pylori and gastric cancer

The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; -6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; provides guidelines for screening at-risk and affected persons with Lynch syndrome; and lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.

Guidelines on genetic evaluation and management of lynch syndrome: A consensus statement by the us multi-society task force on colorectal cancer

BACKGROUND
Although colorectal cancer (CRC) screening guidelines recommend initiating screening at age 50 years, the percentage of cancer cases in younger patients is increasing. To the authors' knowledge, the national treatment patterns and outcomes of these patients are largely unknown.

METHODS
The current study was a population-based, retrospective cohort study of the nationally representative Surveillance, Epidemiology, and End Results registry for patients diagnosed with CRC from 1998 through 2011. Patients were categorized as being younger or older than the recommended screening age. Differences with regard to stage of disease at diagnosis, patterns of therapy, and disease-specific survival were compared between age groups using multinomial regression, multiple regression, Cox proportional hazards regression, and Weibull survival analysis.

RESULTS
Of 258,024 patients with CRC, 37,847 (15%) were aged <50 years. Young patients were more likely to present with regional (relative risk ratio, 1.3; P<.001) or distant (relative risk ratio, 1.5; P<.001) disease. Patients with CRC with distant metastasis in the younger age group were more likely to receive surgical therapy for their primary tumor (adjusted probability: 72% vs 63%; P<.001), and radiotherapy also was more likely in younger patients with CRC (adjusted probability: 53% vs 48%; P<.001). Patients younger than the recommended screening age had better overall disease-specific survival (hazards ratio, 0.77; P<.001), despite a larger percentage of these individuals presenting with advanced disease.

CONCLUSIONS
Patients with CRC diagnosed at age <50 years are more likely to present with advanced-stage disease. However, they receive more aggressive therapy and achieve longer disease-specific survival, despite the greater percentage of patients with advanced-stage disease. These findings suggest the need for improved risk assessment and screening decisions for younger adults. Cancer 2016;122:929–34. © 2016 American Cancer Society.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.29716

Colorectal cancer outcomes and treatment patterns in patients too young for average‐risk screening

Lynch syndrome is a peculiar disease, accounting for 5% of the total burden of colon cancer. Characteristics of this disease are autosomal dominant transmission, early onset, and frequent right colon localization. Diagnostic criteria, aimed to collaborative studies, are based on these features (so called Amsterdam criteria). Lynch syndrome has specific biomolecular features (microsatellite instability); mismatch repair genes have been identified as responsible of this syndrome. Lynch syndrome causes high risk for extracolonic malignancies, particularly for endometrial cancer, supposed to be related to mutation of hMSH2 gene. Another feature of Lynch syndrome tumours is better survival with respect to sporadic counterpart. Genetic test allows identifying the state of mutation carriers and selects the patients to submit to screening. Endoscopic screening has been demonstrated to reduce incidence of colorectal malignancies in this syndrome.

Perluigi Fracasso

Papers

The Lynch syndrome