• Issue
    Volume 148, Issue 11
    2631-2862, E9
    1 June 2021

Issue Information

Free Access

Issue Information

  • Pages: 2631-2637
  • First Published: 05 April 2021

Invited Review

Cancer Epidemiology

Free Access

Dietary fiber intake and risk of gastric cancer: The Japan Public Health Center-based prospective study

  • Pages: 2664-2673
  • First Published: 21 December 2020

What's new?

Since dietary fiber is abundantly contained in whole grains, fruits, and vegetables, it is expected to have beneficial effects on health. But so far, only the association with decreased colorectal cancer risk has been fully established. In a 15-year prospective study with more than 2000 gastric cancer cases from 91 946 Japanese subjects, total dietary fiber intake was not associated with gastric cancer risk. However, a marginally increased association between total fiber intake and gastric cancer incidence in women, and a non-significant inverse trend with cereal fiber intake in men, was observed. Stratification by tumor location did not change the results.

Free Access

Association between changes in mammographic density category and the risk of breast cancer: A nationwide cohort study in East-Asian women

  • Pages: 2674-2684
  • First Published: 23 December 2020

What's new?

Breast density is strongly associated with breast cancer risk. However, in Western countries, the association between density changes and breast cancer risk remains controversial, and no such studies have been reported in East Asia. This Korean study found an association between changes in the BI-RADS density category and the risk of breast cancer. In East-Asian women with a breast cancer family history and high-density category in either the first or second screening mammography, the 5-year risk of developing breast cancer was >1.67%. Longitudinal measures of BI-RADS density may help identify high-risk women, especially those with a breast cancer family history.

Open Access

Stage at diagnosis and survival by stage for the leading childhood cancers in three populations of sub-Saharan Africa

  • Pages: 2685-2691
  • First Published: 12 January 2021

What's new?

To improve child cancer survival rates in sub-Saharan Africa, the first step must be to collect accurate data on incidence and survival. The Toronto Stage Guidelines are a tool to internationally standardize the collection of data on stage of diagnosis of childhood cancers. Here, the authors examined data from three population-based registries on children under 15, and determined that cancer stage at diagnosis was a strong predictor of survival, highlighting the value of population-based registries. The Toronto Stage Guidelines were shown to be feasible for use in a low-resource setting to assess cancer stage at diagnosis.

Open Access

Longitudinal effects of adjuvant chemotherapy and related neuropathy on health utility in stage II and III colon cancer patients: A prospective cohort study

  • Pages: 2702-2711
  • First Published: 18 January 2021

What's new?

Given its potentially serious side effects, patient quality of life should be included in clinical decision-making regarding the administration of adjuvant chemotherapy in stage II/III colon cancer. Using a mixed model which was corrected for relevant covariates, here the authors found a statistically-significant but small decrease in HU of −0.039 during chemotherapy and the following 12 months for patients treated with adjuvant chemotherapy compared to patients without adjuvant chemotherapy. The decrease in HU, which is on the boundary of clinical relevance, appears to be partly related to sensory and motor neuropathy side effects of adjuvant chemotherapy.

Free Access

Associations of fecal microbial profiles with breast cancer and nonmalignant breast disease in the Ghana Breast Health Study

  • Pages: 2712-2723
  • First Published: 18 January 2021

What's new?

The gut microbiome has been shown to affect a variety of physiological systems throughout the body. These authors conducted the largest known study investigating the association of gut bacteria with breast disease in Ghana, where breast cancer incidence is rising. They sequenced the 16S rRNA gene of fecal bacteria among 895 women (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population-based controls). They found that patients with breast cancer and non-malignant breast disease had a similar fecal microbial profile, which differed from that of controls. Microbial alpha diversity was inversely associated with odds of breast cancer and non-malignant breast disease.

Open Access

Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93-01, 2001 and UK-IMPORT database: A report of the SIOP-Renal Tumor Study Group

  • Pages: 2724-2735
  • First Published: 18 January 2021

What's new?

Pediatric renal cell carcinoma (RCC) is a rare malignancy, knowledge of which is based largely on adult RCC. Here, pediatric RCC was retrospectively studied using data from the International Society of Pediatric Oncology – Renal Tumor Study Group (SIOP-RTSG). Pediatric RCC patients had a 5-year overall survival rate of 84.5 percent, with notably lower survival for patients with metastatic disease. In pediatric RCC patients tested for transcription factor E3 and EB, 56.3 percent presented with translocation type. The findings highlight the importance of full registration of pediatric RCCs, with information on germline genetics and transcription factor testing.

Free Access

Alcohol consumption and breast cancer risk in Japan: A pooled analysis of eight population-based cohort studies

  • Pages: 2736-2747
  • First Published: 26 January 2021

What's new?

While alcohol consumption is a well-established risk factor for breast cancer in European populations, associations are less clear for Asian populations. Here, pooled analysis of data for more than 150,000 Japanese women showed that both high frequency alcohol consumption and consumption of large amounts of alcohol are associated with increased breast cancer risk in premenopausal but not postmenopausal women. Associations were evident especially among women who were premenopausal at diagnosis, compared to women who were premenopausal at baseline. Although further study is needed, the findings indicate that among Asian women, alcohol consumption and breast cancer risk have specific associations.

Free Access

Race, ethnicity and risk of second primary contralateral breast cancer in the United States

  • Pages: 2748-2758
  • First Published: 05 February 2021

What's new?

Breast-cancer survivors have an increased risk of developing a second primary, contralateral breast cancer (CBC). Does race or ethnicity influence this risk? In this study, the authors found that Black women do have a higher risk than non-Hispanic white women. However, this increase was not explained by age at diagnosis, receipt of chemotherapy or radiation therapy, socioeconomic or insurance status, or hormone-receptor status of the first breast cancer. Further studies of diverse cohorts are needed to identify modifiable predictors of CBC, in order to develop interventions to reduce this disparity.

Open Access

Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies

  • Pages: 2759-2773
  • First Published: 07 February 2021

What's new?

Alcohol consumption has been causally linked to several cancers, but results for stomach cancer have been inconclusive. In this large, international study, the authors found a positive association between long-term, heavy drinking and non-cardia stomach cancer. This association persisted when data were adjusted for potentially confounding factors such as smoking, body mass index, and Helicobacter pylori infection. A weak inverse association was observed with cardia cancer, suggesting that there may be etiologic differences between non-cardia vs. cardia subtypes.

Cancer Genetics and Epigenetics

Free Access

Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility

  • Pages: 2779-2788
  • First Published: 03 February 2021

What's new?

Long non-coding RNAs (lncRNAs) are thought to contribute to cancer development. Here, the authors searched for new lncRNA variants that are associated with risk of pancreatic ductal adenocarcinoma (PDAC). From analysis of 15,000 individuals, they obtained 67 variants associated with PDAC risk. Some of these were located in genes previously associated with PDAC, an outcome which not only validates the method but could shed light on the functional relevance of these genes. The strongest association was to a variant in the lnc-SMC2-1 gene, and the risk allele is predicted to disrupt cell cycle regulation.

Cancer Therapy and Prevention

Free Access

Effectiveness and safety of nivolumab in patients with advanced melanoma: A multicenter, observational study

  • Pages: 2789-2798
  • First Published: 11 January 2021

What's new?

Clinical trial data support the use of nivolumab in melanoma patients, and the drug received a Temporary Authorization for Use in France. Here, the authors present real-world clinical data on the safety and efficacy of nivolumab collected from 400 patients with unresectable or metastatic melanoma. They found that the safety and efficacy in the real world context was consistent with the profile reported in phase 3 trials. The study also includes data from some sub-populations that may have been underrepresented in the clinical trials.

Free Access

Chemotherapy-based approach is the preferred treatment for sporadic late-onset nemaline myopathy with a monoclonal protein

  • Pages: 2807-2814
  • First Published: 02 February 2021

What's new?

Sporadic late-onset nemaline myopathy (SLONM) associated with monoclonal protein (MP) is a rare aggressive disease. To date, whether SLONM + MP represents a malignancy or dysimmunity and how to treat the disease remain unclear. This study of 53 patients with SLONM + MP shows that a chemotherapy-based approach is superior to non-chemotherapy and should be the preferred treatment with the goal to achieve complete hematologic remission. Based on its clinical/morphological peculiarities, aggressive course, and the superior clinical benefits of chemotherapy, SLONM + MP should be considered as a hematological malignancy, with the presence of MP of clinical rather than undetermined significance in SLONM.

Innovative Tools and Methods

Free Access

Manipulation of focal Wnt activity via synthetic cells in a double-humanized zebrafish model of tumorigenesis

  • Pages: 2815-2824
  • First Published: 24 December 2020

What's new?

Aberrant regulation of the Wnt signaling pathway plays a critical role in cancer pathogenesis. Despite extensive knowledge of this pathway, however, drugs targeting Wnt and Wnt family proteins have shown limited promise. Here, using synthetic cells and a double-humanized zebrafish model system, the authors generated MET-targeting synthetic Notch cells expressing the negative Wnt regulator Dickkopf-1 (DKK1). Upon injection into the hepatic region of zebrafish, synNotch-modified peripheral blood mononuclear cells recognized MET antigens, leading to conditional DKK1 expression and Wnt repression. The findings demonstrate the successful application of synthetic cells and a small animal model to the design of Wnt-targeting therapies.

Molecular Cancer Biology

Open Access

Analysis of nonleukemic cellular subcompartments reconstructs clonal evolution of acute myeloid leukemia and identifies therapy-resistant preleukemic clones

  • Pages: 2825-2838
  • First Published: 07 January 2021

What's new?

Acute myeloid leukemia (AML) develops and progresses through a multistep process, involving the accumulation of multiple molecular abnormalities over time. Little is known, however, about AML-inducing mutations and the role of clones in AML evolution and prognosis. Here, using molecular comparison of leukemic and non-leukemic cells derived from the same bone marrow of AML patients, the authors identified novel point mutations and initiating mutations in AML. Moreover, leukemic evolution was reconstructed from pre-leukemic clones in five patients, four of whom experienced relapse. The findings provide insight into clonal evolution in AML and could aid the identification of novel therapeutic targets.

Open Access

High prevalence of clonal hematopoiesis-type genomic abnormalities in cell-free DNA in invasive gliomas after treatment

  • Pages: 2839-2847
  • First Published: 26 January 2021

What's new?

Tissue biopsy for brain tumors presents significant challenges, making less-invasive molecular profiling with plasma cell-free DNA (cfDNA) an appealing alternative. However, whether alterations detected in cfDNA, including clonal hematopoiesis (CH), reflect processes in brain tumor tissue remains uncertain. In this investigation of CH-associated mutations in plasma-derived cfDNA from patients with invasive gliomas, 87 percent of characterized cfDNA alterations were implicated in CH, indicating that not all cfDNA alterations are cancer-related. In addition, temozolomide/radiation therapy prior to blood draw for cfDNA was associated with potential CH-type cfDNA mutation detection. Potential CH-type cfDNA alterations were an independent predictor of shorter overall survival.

Tumor Markers and Signatures

Free Access

A novel signature predicts recurrence risk and therapeutic response in breast cancer patients

  • Pages: 2848-2856
  • First Published: 14 February 2021

What's new?

Melatonin is associated with delayed breast cancer progression and improved survival in tamoxifen-treated, estrogen receptor (ER)-negative breast cancer patients. Whether acetylserotonin O-methyltransferase (ASMT), which has a key role in melatonin synthesis, influences these effects of melatonin on breast cancer remains unclear. Here, ASMT expression was found to be significantly reduced in human breast cancer tumors. Moreover, patients with relatively high ASMT expression experienced improved relapse-free survival outcomes and increased metastasis-free survival times, particularly following tamoxifen therapy. These findings suggest that in certain subsets of ER-negative patients, knowledge of ASMT expression could be used to better tailor treatment strategies.

Issue Information

Free Access

Issue Information

  • Pages: 2861-2862
  • First Published: 05 April 2021