Vitamin K Gives a Boost to Anti-Cancer Drug Sorafenib By Caroline Seydel

Wei et al., pp. 2949–2958

Patients with liver cancer frequently have other liver disease, such as cirrhosis, making the organ unable to withstand harsh treatments. Researchers, therefore, are eagerly searching for effective treatments that won't harm a fragile liver. Wei et al. found that combining a known anticancer agent with K vitamins can boost the agent's efficacy at lower doses.

Sorafenib is a multi-kinase inhibitor that induces apoptosis in liver cancer, as well as other cancers, but because of its many toxicities, the dosages often need to be lowered. Naturally occurring, non-toxic K vitamins also have been shown to induce apoptosis in liver cancer. Wei et al. considered that combining these two therapies could improve their activity, thus reducing the toxic side effects of sorafenib.

First, the researchers evaluated the duo's effect on cancer cell growth. The two agents together inhibited cell proliferation much more than either could on its own. When they looked at apoptosis, they found that neither agent alone induced cell death at the concentrations tested, but together, they prompted nearly half the cells to kill themselves. Vitamin K, then, appears to enhance the activity of sorafenib, potentially allowing patients to take the drug for longer periods and extend survival.

Illustration 1.

Cells stained with TUNEL to show apoptosis. Treatment with both Vitamin K + sorafenib induced apoptosis more than either alone.

Finding New Mutations Linked to Inherited Colon Cancer By Anne Forde

Gylfe et al., pp. 2974–2980

Some 35% of colorectal cancers are thought to have a hereditary element but known germline mutations account for only a minority of cases. Extensive genome-wide work published by Sjöblom and coworkers in 2006 identified over a thousand somatically mutated genes in colon and breast cancer. Subsequent studies resulted in the list for colon cancer being distilled to 140 candidate cancer genes (CAN genes). The mutations in CAN genes primarily represent somatic mutations but some of these genes have both somatic and germline mutations and thus can offer clues of hereditary susceptibility.

In this report Gylfe et al., take advantage of this phenomenon and evaluate for the first time the role of colorectal CAN genes in familial CRC. A total of 45 tumor samples and healthy tissue from colon cancer patients with a familial history but no known mutations were screened for the top 15 ranked CAN genes. The authors excluded known genes predisposing to CRC such as APC. 22 somatic mutations and 16 germline variants were found. Three of these germline mutations were not found in the population-matched controls: C10orf137, CSMD3 and EPHB6. In silico prediction programs showed that only the mutation within EPHB6 might have a deleterious effect of protein function. C10orf137 mutation was found in an offspring diagnosed with CRC at age 45.

From this study it is clear that tumors have few common mutations; therefore individual genes do not tell the whole story. These novel germline mutations C10orf137, CSMD3 and EPHB6 may contribute to a predisposition to colon cancer; however, this work needs to be extended and validated functionally.

HRT and Ovarian Cancer: Progestin Could Make the Difference By Anne Forde

Hildebrand et al., pp. 2928–2935

Hormone replacement therapy (HRT) is associated with an increased incidence of ovarian cancer in postmenopausal women. In this prospective study with over 54,000 postmenopausal subjects, the authors investigated whether the combination of hormones used and the duration of their current and past use are linked to ovarian cancer.

A total of 297 women in the study developed ovarian cancer. The risk of ovarian cancer was highest among current estrogen-only users with a relative risk (RR) of 2.07 (95% CI 1.50–2.85), which rose by 25% with every additional 5 years of current estrogen-only use. On the other hand, past use led to a modest elevation in risk that was not statistically significant (RR 1.14, 95% CI 0.92–1.41). Combined estrogen and progestin use was not associated with any increased risk in either current or past users. However, the power of the analysis was limited by the fact that relatively small numbers of women received more than 5 years of estrogen plus progestin treatment.

This study supports the theory that, on their own, estrogens can be more detrimental to the ovaries than estrogen combined with progestin. Progestin, therefore, is thought to have a protective effect against ovarian cancer as seen with oral contraceptive use. The authors concede that the relative rarity of ovarian cancer compared to other common HRT risks means that these results may not influence the decision to use HRT or not. However, due to the high mortality associated with ovarian cancer, current and past users of estrogen only HRT may require closer monitoring.

New Resources Available on Cancer Global Incidences By Anne Forde

Parkin et al., pp. 2918–2927

Ferlay et al., pp. 2893–2917

Since the 1960s, the Cancer Incidence in Five Continents (CI5) has combined incidence from population-based cancer registries worldwide. Parkin and colleagues now present CI5—volume CI5 I-IX—which comprises two public domain websites with past volumes, updated data and some new web-based functions.

Illustration 2.

Estimated numbers of new cancers incidence and mortality in men (a) and women (b) in 2008.

One example of the power of this resource is the online analysis option that allows users to create tables of incidence rates by year rather than a specific CI5 volume period. Graphics facilities enable users to create, for example, specific curves based on age or cancer subtype. In their paper, the authors illustrate cervical cancer incidence by histological subtype and show that the decline in cervical cancer is largely due to a decline in squamous cell tumors (SCC) with almost no change in adenocarcinoma. This result and the power of CI5 I-IX are important not only to further study cancer incidence but also to evaluate and plan and modify cancer control programs such as cervical screening.

In a related article, Ferlay et al., present the 2008 GLOBOCAN and highlight the global incidence and mortality of the most common cancer types in 20 global regions in 2008. Estimates of the sex- and age-specific incidences were calculated by one of several methods, depending on the availability and accuracy of the cancer incidence or mortality statistics.

The authors estimated there were 12.7 million new cases and 7.6 million cancer deaths worldwide in 2008. The numbers of new cases and death in men and women are also illustrated: the most common cancer in terms of incidence and cancer death is lung cancer. This is followed by breast cancer, which has the second highest incidence but only ranks 5th in mortality. Colorectal cancer holds 3rd place in incidence rates. Stomach and liver cancer ranked in 5th and 6th places in incidence but have higher in mortality rates than colorectal cancer. Incidence rates of cancers differed greatly in across geographical regions, particularly for men.

These two repositories represent highly valuable resources for cancer research and for planning and evaluation of cancer programmes.