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      Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine

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          Abstract

          The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.

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          Most cited references40

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          Cancer statistics, 2019

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.
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            Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome.

            Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome. To estimate the age-specific cumulative risks of developing various tumors using a large series of families with mutations of the MLH1, MSH2, and MSH6 genes. Families with Lynch syndrome enrolled between January 1, 2006, and December 31, 2009, from 40 French cancer genetics clinics participating in the ERISCAM (Estimation des Risques de Cancer chez les porteurs de mutation des gènes MMR) study; 537 families with segregating mutated genes (248 with MLH1; 256 with MSH2; and 33 with MSH6) were analyzed. Age-specific cumulative cancer risks estimated using the genotype restricted likelihood (GRL) method accounting for ascertainment bias. Significant differences in estimated cumulative cancer risk were found between the 3 mutated genes (P = .01). The estimated cumulative risks of colorectal cancer by age 70 years were 41% (95% confidence intervals [CI], 25%-70%) for MLH1 mutation carriers, 48% (95% CI, 30%-77%) for MSH2, and 12% (95% CI, 8%-22%) for MSH6. For endometrial cancer, corresponding risks were 54% (95% CI, 20%-80%), 21% (95% CI, 8%-77%), and 16% (95% CI, 8%-32%). For ovarian cancer, they were 20% (95% CI, 1%-65%), 24% (95% CI, 3%-52%), and 1% (95% CI, 0%-3%). The estimated cumulative risks by age 40 years did not exceed 2% (95% CI, 0%-7%) for endometrial cancer nor 1% (95% CI, 0%-3%) for ovarian cancer, irrespective of the gene. The estimated lifetime risks for other tumor types did not exceed 3% with any of the gene mutations. MSH6 mutations are associated with markedly lower cancer risks than MLH1 or MSH2 mutations. Lifetime ovarian and endometrial cancer risks associated with MLH1 or MSH2 mutations were high but do not increase appreciably until after the age of 40 years.
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              Very high risk of cancer in familial Peutz-Jeghers syndrome.

              The Peutz-Jeghers syndrome (PJS) is an autosomal dominant polyposis disorder with increased risk of multiple cancers, but literature estimates of risk vary. We performed an individual patient meta-analysis to determine the relative risk (RR) of cancer in patients with PJS compared with the general population based on 210 individuals described in 6 publications. For patients with PJS, the RR for all cancers was 15.2 (95% confidence limits [CL], 2, 19). A statistically significant increase of RR was noted for esophagus (57; CL, 2.5, 557), stomach (213; CL, 96, 368), small intestine (520; CL, 220, 1306), colon (84; CL, 47, 137), pancreas (132; CL, 44, 261), lung (17.0; CL, 5.4, 39), breast (15.2; CL, 7.6, 27), uterus (16.0; CL, 1.9, 56), ovary (27; CL, 7.3, 68), but not testicular or cervical malignancies. Cumulative risk for all cancer was 93% from age 15 to 64 years old. Patients with PJS are at very high relative and absolute risk for gastrointestinal and nongastrointestinal cancers.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                21 October 2022
                21 October 2022
                : 28
                : 39
                : 5658-5665
                Affiliations
                Department of Gastroenterology, Chiba Hokusoh Hospital, Nippon Medical School, Chiba 270-1694, Japan. s-fujimori@ 123456nms.ac.jp
                Department of Gastroenterology, Chiba Hokusoh Hospital, Nippon Medical School, Chiba 270-1694, Japan
                Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
                Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
                Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
                Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
                Department of Gastroenterology, Tama-Nagayama Hospital, Nippon Medical School, Tokyo 206-0025, Japan
                Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
                Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
                Author notes

                Author contributions: Fujimori S contributed to the writing of this paper; Hamakubo R, Hoshimoto A, Nishimoto T, Omori J, and Tanaka S performed the small intestinal examinations; Akimoto N and Tatsuguchi A conducted the pathological examinations; Iwakiri K gave advice for the writing of the paper.

                Corresponding author: Shunji Fujimori, AGAF, MD, PhD, Director, Department of Gastroenterology, Chiba Hokusoh Hospital, Nippon Medical School, 1715 Kamagari, Inzai-City, Chiba 270-1694, Japan. s-fujimori@ 123456nms.ac.jp

                Article
                jWJG.v28.i39.pg5658
                10.3748/wjg.v28.i39.5658
                9627424
                36338888
                20eff5f6-9400-4d68-8958-b2b1bc8124e0
                ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 5 August 2022
                : 18 September 2022
                : 11 October 2022
                Categories
                Opinion Review

                small intestine,large intestine,adenocarcinoma,risk factor,carcinogenesis

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