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In This Issue
Breast Cancer Risk and Calcium and Vitamin D IntakeObservational studies have shown an association between higher calcium and vitamin D intake and reduced breast cancer risk, but no randomized trial has tested this. Chlebowski et al. (p. 1581) compared the incidence of invasive breast cancer among 36,282 postmenopausal women who were randomly assigned to take 1,000 mg of calcium with 400 IU of vitamin D3 or placebo as part of the Women's Health Initiative. Invasive cancer incidence was similar in both groups. The authors conclude that these findings do not support a relationship between vitamin D intake and decreased breast cancer risk.
In an editorial, Speers and Brown (p.1562) write that because results of preclinical studies suggest that vitamin D may be a preventive agent for breast cancer, further study is still warranted.
Cigarette Smoke and Expression of Potential Lung Cancer Gene
Overexpressed in Lung Cancer 1 (OLC1) is a gene whose expression is higher in squamous cell carcinoma (SCC) than in normal lung tissue. To determine whether OLC1 is a lung cancer oncogene and whether its expression is regulated by cigarette smoke, Yuan et al. (p. 1592) assayed OLC1 protein expression in samples from 559 lung cancer patients and compared expression in samples of 371 SCC patients with and without a smoking history. They also compared OLC1 expression in lung cancer and human bronchial epithelial cells that had been treated with cigarette smoke or vehicle control and compared tumor formation in athymic mice that were injected with transformed mouse fibroblast cells or the same type of cells engineered to overexpress OLC1. OLC1 protein overexpression was detected in 83.4% of lung cancers and in more samples from patients with a smoking history (77%) than without (46%). Exposure to cigarette smoke induced OLC1 expression, and OLC1 overexpression led to tumor formation in mice.
In an editorial, Kaye (p. 1564) writes that these findings should stimulate further research into the functional role of OLC1.
Isolated Breast Cancer Cells in Sentinel Lymph Node
Although associations between non-sentinel lymph node (non-SLN) involvement and isolated tumor cells in the SLN have been reported, recommendations for use of axillary lymph node dissection (ALND) have been inconsistent. Van Deurzen et al. (p. 1574) conducted a systematic review to provide recommendations for the use of ALND in patients with isolated tumor cells in their SLN. Studies were heterogeneous and reported a wide range of non-SLN involvement (including isolated tumor cells or micro- or macrometastases). The overall pooled risk estimate was marginally higher than the risk of a false-negative SLN biopsy examination but marginally lower than the risk of non-SLN metastases in patients with micrometastases, who are eligible for ALND. A substantial proportion of these non-SLNs contain macrometastases. The authors conclude that patients with isolated tumor cells in the SLN without other indications for adjuvant systemic therapy might be candidates for ALND.
Seven-in-Absentia Homolog 2 and Lung Cancer
The most common genetic lesions in non–small-cell lung cancers include activating mutations in the epidermal growth factor receptor (EGFR) gene and in the K-RAS gene. A human homologue of Drosophila seven-in-absentia—SIAH-2—is a ubiquitin E3 ligase and a conserved downstream component of the EGFR/RAS pathway that is required for mammalian RAS signal transduction. Ahmed et al. (p. 1606) examined whether targeting SIAH-2 could block lung tumor growth and cell proliferation. They assayed the effects of lentivirus-mediated expression of a dominant-negative protease-deficient mutant of SIAH-2 and of a short hairpin RNA–mediated gene knockdown in normal human lung epithelial cells, in human lung cancer cells, and in nude mice. They found that SIAH-2 deficiency in human lung cancer cells reduced MAPK signaling, inhibited cell proliferation, and increased apoptosis compared with SIAH-proficient cells. SIAH-2 deficiency also reduced anchorage-independent growth of lung cancer cells and blocked the growth of lung cancer cell–derived tumors in mice.
Lysophosphatidic Acid Signaling in Ovarian Cancer
Lysophosphatidic acid (LPA) is present at high levels in the ascitic fluid of ovarian cancer patients, and two of its receptors, LPA2 and LPA3, are aberrantly expressed in ovarian cancer cells. Yu et al. (p. 1630) inhibited or increased expression of LPA1, LPA2, and LPA3 in ovarian cancer cells. They observed that the invasiveness and cytokine production of these cells was dependent on the expression of each of the LPA receptors. Consistent with these results, mice injected with ovarian cancer cells engineered to express individual LPA receptors had more metastases and died sooner than mice injected with ovarian cancer cells expressing beta-galactosidase. The authors suggest that receptor-mediated signaling by LPA in human ovarian cancer warrants continued investigation.
Breast Cancer in Younger Women
Postmenopausal breast cancers are associated with hormone use and mammography screening, but less attention has focused on cancers in younger women. Brinton et al. (p. 1643) analyzed incidence trends of more than 387,000 breast cancers reported to the National Cancer Institute's SEER Program 13-Registry database during 1992–2004. Breast cancer incidence was higher among white women than black women after age 40, but the reverse was true for younger women. This crossover was largely restricted to cancers with favorable tumor characteristics. The annual percentage change in invasive breast cancer incidence decreased modestly among older women but increased among younger white women.
Squamous Cell Carcinomas in Fanconi Anemia Patients
Fanconi anemia is an inherited disease characterized by congenital abnormalities, bone marrow failure, and a predisposition to develop cancer, particularly squamous cell carcinomas (SCCs) in the head and neck and anogenital regions. To see if HPV involvement is a common feature of Fanconi anemia SCCs, van Zeeburg et al. (p. 1649) examined a panel of 21 SCCs from 19 Fanconi anemia patients, focusing on the presence of HPV DNA and several surrogate markers of HPV involvement. HPV DNA and all of the surrogate markers analyzed were detected in only two SCCs (both anogenital), but in none of the 16 head and neck SCCs. The patterns of allelic loss for the Fanconi anemia SCCs closely resembled those found in most sporadic SCCs, which are not caused by HPV infection. The authors conclude that in this cohort HPV might play a role in anogenital, not head and neck, SCCs.
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Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2008 100: 1574-1580.
J Natl Cancer Inst 2008 100: 1643-1648.
J Natl Cancer Inst 2008 100: 1581-1591.
J Natl Cancer Inst 2008 100: 1606-1629.
J Natl Cancer Inst 2008 100: 1649-1653.
J Natl Cancer Inst 2008 100: 1630-1642.
J Natl Cancer Inst 2008 100: 1592-1605.
J Natl Cancer Inst 2008 100: 1564-1565.
J Natl Cancer Inst 2008 100: 1562-1564.
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