Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests.

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Global cancer statistics, 2012

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Food in the Anthropocene: the EAT–Lancet Commission on healthy diets from sustainable food systems

Statistical methods in cancer research

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.29367

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.

The Mammary Prevention 3 (MAP.3) placebo-controlled randomized trial in 4,560 high-risk postmenopausal women showed a 65% reduction in invasive breast cancer with the use of exemestane at 35 months median follow-up. Few differences in adverse events were observed between the arms, suggesting a promising risk:benefit balance with exemestane for use in chemoprevention. Yet, the MAP.3 design and implementation raise concerns regarding limited data maturity and not prospectively including key bone-related and other toxicities as study end points. Exemestane for prevention is juxtaposed against selective estrogen receptor modulators and the other aromatase inhibitors. Additional issues for prevention, including the influence of obesity, alternative dosing, and biomarker use in phase III trials, are addressed.

Significance: The recently completed MAP.3 trial of exemestane for breast cancer prevention offers a potential new standard for pharmaceutical risk reduction in high-risk postmenopausal women. In addition to describing key findings from the publication of MAP.3 and related trials, our review undertakes a detailed analysis of the strengths and weaknesses of MAP.3 as well as the implications for future prevention research. Cancer Discovery; 2(1) ; 25–40. ©2012 AACR .

https://cancerdiscovery.aacrjournals.org/content/candisc/2/1/25.full.pdf

Exemestane for breast cancer prevention: a critical shift?

Prostate cancer continues to be both a major health threat, especially among African-American men, and a public health burden. However, growing evidence suggests that selenium and vitamin E may decrease the risk of this disease. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), a phase III randomized, placebo-controlled study, is designed to determine whether selenium and vitamin E, alone or in combination, decrease the risk of prostate cancer in healthy men. SELECT opened to accrual on 25 July 2001 in more than 400 clinical sites across the United States, Puerto Rico, and Canada; the goal was to randomize 32,400 men. Accrual was completed in June 2004, 2 years ahead of schedule, with a total of 35,534 men randomized. Eligibility require ments include age of at least 55 years (African-American men at least 50 years), and no evidence of prostate cancer as determined by a serum PSA level of no more than 4 ng/ml and a digital rectal exam (DRE) not suspicious for prostate cancer. Participants were randomized to receive selenium (200 μg/ day of l -selenomethionine) and/or vitamin E (400 IU/day of all-rac-alpha-tocopheryl acetate) supplementation for a minimum of 7 years (maximum of 12 years). The rationale for choosing these agents was based on preclinical data as well as analyses of secondary endpoints in cancer prevention clinical trials. The primary endpoint of SELECT is occurrence of prostate cancer based on community standards of diagnosis. Several other non-cancer endpoints are also being explored.

Selenium and Vitamin E Cancer Prevention Trial: a nutrient approach to prostate cancer prevention.

Clinical trials to evaluate interventions for cancer prevention are designed as early (phase I, IIa, and IIb) or late-phase studies. Whereas the former are small and generally rely on intermediate endpoint biomarkers of carcinogenesis, the latter are large-scale, long-term, randomized, phase III studies that address endpoints such as cancer incidence. The Breast Cancer Prevention Trial, P-1, conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), is discussed as an example of a large, extended, phase III trial designed to answer the question of whether tamoxifen reduces the incidence of breast cancer in women who are at increased risk for the disease.

https://www.hemonc.theclinics.com/article/S0889-8588(05)70039-3/pdf

Phase III, large-scale chemoprevention trials. Approach to chemoprevention clinical trials and phase III clinical trial of tamoxifen as a chemopreventive for breast cancer--the US National Cancer Institute experience.

In 1998, the concept of breast cancer prevention became a reality with the approval of tamoxifen to reduce the risk of developing breast cancer in women at increased risk for the disease. This approval was based on decades of research on selective estrogen receptor modulators providing an understanding of the role of the estrogen receptor in breast cell growth, and an appreciation of the carcinogenic process. Although results from the Breast Cancer Prevention Trial demonstrated a 49% reduction in breast cancer in women at increased risk, there were associated toxicities related to the estrogenic effects of tamoxifen; that is, deep vein thrombosis, pulmonary embolism, and endometrial cancer. In an effort to improve its benefit-risk profile, tamoxifen is now being compared with raloxifene, a selective estrogen receptor modulator approved for the treatment and prevention of osteoporosis. This equivalency prevention Study of Tamoxifen and Raloxifene completed accrual of 19 747 high-risk postmenopausal women in November 2004. Meanwhile, another class of estrogen-directed drugs, the aromatase inhibitors, have shown efficacy in breast cancer adjuvant trials, spawning a number of prevention trials that have recently been initiated. As with breast cancer the hormonal contribution to prostate carcinogenesis was the basis for the Prostate Cancer Prevention Trial which showed that finasteride, an androgen antagonist, reduces the incidence of prostate cancer compared to placebo.

Leslie G. Ford

Papers

Exemestane for breast cancer prevention: a critical shift?

Selenium and Vitamin E Cancer Prevention Trial: a nutrient approach to prostate cancer prevention.

Phase III, large-scale chemoprevention trials. Approach to chemoprevention clinical trials and phase III clinical trial of tamoxifen as a chemopreventive for breast cancer--the US National Cancer Institute experience.

Hormonal interventions to prevent hormonal cancers: breast and prostate cancers.

Breast cancer prevention trials: large and small trials.