Roberta McKean-Cowdin

Declining Cancer Rates in the 1990s

PURPOSE To provide evidence of a substantial decline in cancer rates for the period 1991 through 1995 and characterize major risk factors that seem to be driving secular trends in cancer mortality and incidence. DESIGN Incidence and mortality rates were calculated using national surveillance data collected through the Surveillance, Epidemiology, and End Results (SEER) program and the National Center for Health Statistics. RESULTS All-sites cancer incidence and mortality fell in the period 1991 through 1995; this decline is largely attributable to decreases in the smoking-related cancers, especially lung cancer. Of the 20 leading incident cancers today, both incidence and mortality are decreasing among 11 sites for men and 12 for women. In men, the decline in mortality has been notable and is especially apparent for the smoking-related cancers, including those of the lung, oral cavity and pharynx, larynx, and, to a lesser extent, bladder. In women, all-sites mortality decreased only approximately 0.4% from 1991 through 1995. Three cancers continued to show substantial increases in mortality through 1995 for both men and women (liver, multiple myeloma, and non-Hodgkins lymphoma), while incidence rates continued to climb for liver cancer, non-Hodgkins lymphoma, and melanoma. CONCLUSION Data from the SEER program on recent trends in cancer incidence and mortality show that cancer rates are generally on the decline, largely because of reductions in smoking-related cancers. A consistent increase in mortality rates due to liver cancer poses a new health care challenge, one that will require the development of an effective treatment for individuals currently infected with hepatitis C or B to prevent mortality rates from continuing to increase.

IGF1 genotype, mean plasma level and breast cancer risk in the Hawaii/Los Angeles multiethnic cohort

The insulin-like growth factor 1 gene (IGF1) is a strong candidate gene for a breast cancer susceptibility model. We investigated a dinucleotide repeat 969 bp upstream from the transcription start site of the IGF1 gene for possible associations with plasma IGF1 levels and breast cancer risk in a multiethnic group of postmenopausal women. Furthermore, we investigated the relation between race/ethnicity, mean plasma IGF1 levels and breast cancer rates in the Hawaii/Los Angeles Multiethnic Cohort. The mean age-adjusted IGF1 level among Latino-American women, 116 ng ml−1, was statistically significantly lower than the mean age-adjusted IGF1 levels for each of the three other racial/ethnic groups, African-American, Japanese-American and Non-Latino White women (146, 144 and 145 ng ml−1, respectively) (P<0.0001). Latino-American women have the lowest breast cancer rates of any racial/ethnic group in the cohort. These results support the investigation of an expansion of the hypothesis for an important role of IGF1 in breast cancer tumorigenesis to different racial/ethnic groups and to postmenopausal women. It is unlikely that any involvement of IGF1 in breast cancer aetiology is mediated by the IGF1 dinucleotide repeat polymorphism, which was not significantly associated with circulating IGF1 levels nor breast cancer risk in this study. Research into relevant determinants of IGF1 levels in the blood must continue.

Central and Peripheral Visual Impairment and the Risk of Falls and Falls with Injury

OBJECTIVE To evaluate whether central (CVI) and peripheral visual impairment (PVI) are independent risk factors for falls and falls with injury 4 years later. DESIGN Population-based, prospective cohort study. PARTICIPANTS A population-based sample of 3203 adult Latinos. METHODS Baseline presenting binocular central distance acuity was measured and impairment was classified as mild (20/40-20/63) or moderate/severe (<or=20/80). Peripheral visual impairment was classified as mild (-6 dB < mean deviation < -2 dB in worse eye), moderate/severe (mean deviation <or=-6 dB in worse eye). MAIN OUTCOME MEASURES Falls and falls with injury in the past 12 months were assessed by self-report at the 4-year follow-up visit. RESULTS Out of 3203 individuals, 19% reported falls and 10% falls with injury 4 years after the baseline examination; participants with falls were more likely to be >or=60 years of age, be female, report lower income, have >2 comorbidities, report alcohol use, report wearing bifocal glasses, and report obesity. Among those who reported falls, 7% had CVI (visual acuity >20/40) compared with 4% who did not report falls; and 49% had PVI (mean deviation < -2 dB) compared with 39% of those who did not report falls (both P<0.0001). After adjusting for confounders, moderate to severe CVI and PVI were associated with increased risk for falls (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.02-5.45; P(trend) = 0.04; and OR, 1.42; 95% CI, 1.06-1.91l P(trend) = 0.01, respectively) and with falls with injury (OR, 2.76; 95% CI, 1.10-7.02; P(value) = 0.03; and OR, 1.40; 95% CI, 0.94-2.05 P(trend) = 0.04, respectively). CONCLUSIONS Both CVI and PVI were independently associated with increased risk for falls and falls with injury 4 years after the initial examination in a dose-response manner. Although vision-related interventions for preventing falls have mainly focused on correcting CVI, this study suggests that targeting both central and peripheral components may be necessary to effectively reduce rates of falls and falls with injury related to vision loss.

Associations between Polymorphisms in DNA Repair Genes and Glioblastoma

A pooled analysis was conducted to examine the association between select variants in DNA repair genes and glioblastoma multiforme, the most common and deadliest form of adult brain tumors. Genetic data for ∼1,000 glioblastoma multiforme cases and 2,000 controls were combined from four centers in the United States that have conducted case-control studies on adult glioblastoma multiforme, including the National Cancer Institute, the National Institute for Occupational Safety and Health, the University of Texas M. D. Anderson Cancer Center, and the University of California at San Francisco. Twelve DNA repair single-nucleotide polymorphisms were selected for investigation in the pilot collaborative project. The C allele of the PARP1 rs1136410 variant was associated with a 20% reduction in risk for glioblastoma multiforme (odds ratioCT or CC, 0.80; 95% confidence interval, 0.67-0.95). A 44% increase in risk for glioblastoma multiforme was found for individuals homozygous for the G allele of the PRKDC rs7003908 variant (odds ratioGG, 1.44; 95% confidence interval, 1.13-1.84); there was a statistically significant trend (P = 0.009) with increasing number of G alleles. A significant, protective effect was found when three single-nucleotide polymorphisms (ERCC2 rs13181, ERCC1 rs3212986, and GLTSCR1 rs1035938) located near each other on chromosome 19 were modeled as a haplotype. The most common haplotype (AGC) was associated with a 23% reduction in risk (P = 0.03) compared with all other haplotypes combined. Few studies have reported on the associations between variants in DNA repair genes and brain tumors, and few specifically have examined their impact on glioblastoma multiforme. Our results suggest that common variation in DNA repair genes may be associated with risk for glioblastoma multiforme. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1118–26)

Risk Factors Associated with Childhood Strabismus: The Multi-Ethnic Pediatric Eye Disease and Baltimore Pediatric Eye Disease Studies

OBJECTIVE To investigate risk factors associated with esotropia or exotropia in infants and young children. DESIGN Population-based cross-sectional prevalence study. PARTICIPANTS Population-based samples of 9970 children 6 to 72 months of age from California and Maryland. METHODS Participants were preschool African-American, Hispanic, and non-Hispanic white children participating in the Multi-Ethnic Pediatric Eye Disease Study and the Baltimore Eye Disease Study. Data were obtained by parental interview and ocular examination. Odd ratios and 95% confidence intervals were calculated to evaluate the association of demographic, behavioral, and clinical risk factors with esotropia and exotropia. MAIN OUTCOME MEASURES Odds ratios (ORs) for various risk factors associated with esotropia or exotropia diagnosis based on cover testing. RESULTS In multivariate logistic regression analysis, esotropia was associated independently with prematurity, maternal smoking during pregnancy, older preschool age (48-72 months), anisometropia, and hyperopia. There was a severity-dependent association of hyperopia with the prevalence of esotropia, with ORs increasing from 6.4 for 2.00 diopters (D) to less than 3.00 D of hyperopia, to 122.0 for 5.00 D or more of hyperopia. Exotropia was associated with prematurity, maternal smoking during pregnancy, family history of strabismus, female sex, astigmatism (OR, 2.5 for 1.50 to <2.50 D of astigmatism, and 5.9 for ≥2.5 D of astigmatism), and anisoastigmatism in the J0 component (OR, ≥2 for J0 anisoastigmatism of ≥0.25 D). CONCLUSIONS Prematurity and maternal smoking during pregnancy are associated with a higher risk of having esotropia and exotropia. Refractive error is associated in a severity-dependent manner to the prevalence of esotropia and exotropia. Because refractive error is correctable, these risk associations should be considered when developing guidelines for the screening and management of refractive error in infants and young children. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Effect of Reproductive Factors and Oral Contraceptives on Breast Cancer Risk in BRCA1/2 Mutation Carriers and Noncarriers: Results from a Population-Based Study

Background: Multiparity and breast-feeding reduce breast cancer risk, whereas oral contraceptive use may slightly increase breast cancer risk in the general population. However, the effects of these factors in BRCA1 and BRCA2 mutation carriers are less clear. Methods: Case patients were 1,469 women from Los Angeles County ages 20 to 49 years with newly diagnosed breast cancer. Control subjects were 444 women without breast cancer, individually matched to a subset of cases on race, age, and neighborhood. BRCA1/2 genes were sequenced in the cases, and odds ratios of breast cancer associated with various reproductive and hormonal factors in BRCA1/2 mutation carriers and noncarriers were estimated using multivariable logistic regression. Results: Ninety-four women had a deleterious BRCA1 or BRCA2 mutation. Number of full-term pregnancies was inversely associated with breast cancer risk regardless of BRCA1/2 mutation status. Longer breast-feeding duration was protective among noncarriers but not among mutation carriers; however, this apparent effect modification was not statistically significant (P = 0.23). Neither oral contraceptive use overall nor the use of low-dose oral contraceptives was associated with an increased risk of breast cancer in any subgroup. Conclusions: Our results suggest that parity protects against breast cancer in BRCA1/2 mutation carriers, whereas breast-feeding does not. Our data suggest no association between oral contraceptive use and breast cancer risk in BRCA1/2 mutation carriers. Further confirmation that currently available low-dose oral contraceptives do not increase breast cancer risk in carriers is important from a public health perspective given the high prevalence of oral contraceptive use in the United States. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3170–8)

Characteristics of Triple-Negative Breast Cancer in Patients With a BRCA1 Mutation: Results From a Population-Based Study of Young Women

PURPOSE Triple-negative breast cancers (TNBCs) are tumors with low or no expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. These tumors have a poor prognosis, remain a clinical challenge, and are more common among women with BRCA1 mutations. We tested whether there are distinguishing features of TNBC after BRCA1 mutation status has been taken into account. PATIENTS AND METHODS We sequenced BRCA1 and BRCA2 genes in a population-based sample of 1,469 patients with incident breast cancer age 20 to 49 years from Los Angeles County (California). Information on tumor receptor status was available for 1,167 women. Clinical, pathologic, and hormone-related lifestyle characteristics were compared across patient subgroups defined by BRCA1 mutation status and triple-negative receptor status. RESULTS Forty-eight percent of BRCA1 mutation carriers had TNBC compared with only 12% of noncarriers. Within BRCA1 mutation carriers, as well as within noncarriers, triple-negative receptor status was associated with younger age at diagnosis and higher tumor grade. Among women without a BRCA1 mutation, we observed that women with TNBC had higher premenopausal body mass index and earlier age at first full-term pregnancy than those with non-TNBC. Age at menarche and other reproductive factors were not associated with triple-negative status regardless of BRCA1 mutation status. Within BRCA1 mutation carriers, Ashkenazi Jewish women were about five times more likely to have TNBC than non-Ashkenazi Jewish women. CONCLUSION Our results suggest that among BRCA1 mutation carriers, as among noncarriers, there are unique characteristics associated with the triple-negative subtype. The findings in Ashkenazi Jewish BRCA1 mutation carriers should be confirmed.

Childhood Brain Tumor Epidemiology: A Brain Tumor Epidemiology Consortium Review

Childhood brain tumors are the most common pediatric solid tumor and include several histologic subtypes. Although progress has been made in improving survival rates for some subtypes, understanding of risk factors for childhood brain tumors remains limited to a few genetic syndromes and ionizing radiation to the head and neck. In this report, we review descriptive and analytical epidemiology childhood brain tumor studies from the past decade and highlight priority areas for future epidemiology investigations and methodological work that is needed to advance our understanding of childhood brain tumor causes. Specifically, we summarize the results of a review of studies published since 2004 that have analyzed incidence and survival in different international regions and that have examined potential genetic, immune system, developmental and birth characteristics, and environmental risk factors. Cancer Epidemiol Biomarkers Prev; 23(12); 2716–36. ©2014 AACR.

American Brain Tumor Association Adolescent and Young Adult Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012.

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH USA Central Brain Tumor Registry of the United States, Hinsdale, IL USA Department of Pediatric Hematology-Oncology, Rainbow Babies and Children s Hospital, Cleveland, OH USA Division of Hematology, Oncology and BMT, Nationwide Children’s Hospital and The Ohio State University, Columbus, OH USA School of Public Health, University of Memphis, Memphis, TN USA Keck School of Medicine, University of Southern California, Los Angeles, CA USA Department of Pediatric Hematology and Oncology, Cleveland Clinic Children’s Hospital, Cleveland, OH USA Solon High School, Solon, OH USA

Ethnic differences in post-menopausal plasma oestrogen levels: high oestrone levels in Japanese-American women despite low weight

Breast cancer incidence in Japanese-American women is approaching that of US Whites. We investigated whether this shift is paralleled by similar post-menopausal plasma hormone levels in the two ethnic groups. We also included African-American and Latina women to further our understanding of possible ethnic differences in oestrogen metabolism. We measured androstenedione (A), oestrone (E1) and oestradiol (E2) in 30 Japanese-American, 39 non-Latina White (‘White’), 66 African-American and 58 Latina women. The (age-adjusted) geometric mean E1 levels were 34 pg ml–1 in Japanese-Americans, 28 pg ml–1 in Whites, 35 pg ml–1 in African-Americans and 31 pg ml–1in Latinas. After adjustment for body mass index, Japanese-Americans had the highest mean E1 value of all groups and this was statistically significantly greater than the value for Whites (Pt-test= 0.05). The geometric mean A concentrations were also highest in Japanese-Americans. There was little ethnic difference in E2 levels. In conclusion, post-menopausal plasma oestrogen levels in Japanese-American women are at least as high as those in Whites.