Andrew F. Olshan

Comparison of a Trial of Labor with an Elective Second Cesarean Section

BACKGROUND In an attempt to reduce the rate of cesarean section, obstetricians now offer a trial of labor to pregnant women who have had a previous cesarean section. Although a trial of labor is usually successful and is relatively safe, few studies have directly addressed the maternal and perinatal morbidity and mortality associated with this method of delivery. METHODS We performed a population-based, longitudinal study of 6138 women in Nova Scotia who had previously undergone cesarean section and had delivered a singleton live infant in the period from 1986 through 1992. RESULTS A total of 3249 women elected a trial of labor, and 2889 women chose to undergo a second cesarean section. There were no maternal deaths. The overall rate of maternal morbidity was 8.1 percent; 1.3 percent had major complications (a need for hysterectomy, uterine rupture, or operative injury) and 6.9 percent had minor complications (puerperal fever, a need for blood transfusion, or abdominal-wound infection). Although the overall rate of maternal complications did not differ significantly between women who chose a trial of labor and the women who elected cesarean section (odds ratio for the trial-of-labor group, 0.9; 95 percent confidence interval, 0.8 to 1.1), major complications were nearly twice as likely among women undergoing a trial of labor (odds ratio, 1.8; 95 percent confidence interval, 1.1 to 3.0). Apgar scores, admission to the neonatal intensive care unit, and perinatal mortality were similar among the infants whose mothers had a trial of labor and those whose mothers underwent elective cesarean section. CONCLUSION Among pregnant women who have had a cesarean section, major maternal complications are almost twice as likely among those whose deliveries are managed with a trial of labor as among those who undergo an elective second cesarean section.

Interaction between tobacco and alcohol use and the risk of head and neck cancer: Pooled analysis in the international head and neck cancer Epidemiology consortium

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (ψ) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (ψ = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases <45 years, 73% for cases >60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50)

Human papillomavirus and head and neck cancer: Epidemiology and molecular biology

Human papillomaviruses (HPV) are known to cause cancers of the cervix and other anogenital tract sites. Molecular biology has provided some evidence as to the specific mechanisms involved in the HPV‐related carcinogenesis. Epidemiologic and molecular biology studies have also suggested that HPV infection may be associated with cancers of the head and neck.

Occupational exposure assessment in case-control studies: opportunities for improvement

Community based case–control studies are an efficient means to study disease aetiologies, and may be the only practical means to investigate rare diseases. However, exposure assessment remains problematic. We review the literature on the validity and reliability of common case–control exposure assessment methods: occupational histories, job–exposure matrices (JEMs), self reported exposures, and expert assessments. Given the variable quality of current exposure assessment techniques, we suggest methods to improve assessments, including the incorporation of hygiene measurements: using data from administrative exposure databases; using results of studies identifying determinants of exposure to develop questionnaires; and where reasonable given latency and biological half life considerations, directly measuring exposures of study subjects.

Paternal age and the risk of birth defects in offspring.

Previous studies have shown that advanced paternal age is associated with an increase in new dominant mutations that may result in some rare congenital anomalies or syndromes in the offspring. Nevertheless, few epidemiologic studies have evaluated the effect of paternal age on the risk of more common birth defects. We examined data from the British Columbia Health Surveillance Registry, which included a total of 9,660 cases of birth defects (22 specific defect groups). We chose matched controls from the birth files of British Columbia (1952–1973). With the exception of an unusual change in direction in the 45–49 years age category, we found a general pattern of increasing relative risk estimates (adjusted for maternal age and other factors) with increasing paternal age for neural tube defects, congenital cataracts, reduction defects of the upper limb, and Down syndrome. For example, the adjusted relative risk estimates for neural tube defects in the offspring were 1.2 (for fathers age 30–34 years relative to 25–29 years); 1.3 (35–39); 1.6 (40–44); 0.6 (45–49); and 2.3 (men 50 years and older). Men under 20 years of age were also at increased risk for fathering children with birth defects such as neural tube defects, hypospadias, cystic kidney, and Down syndrome. We hypothesize that among certain commonly observed birth defects a subgroup of cases may be due to new, unrecognized dominant mutations.

Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk

BACKGROUND Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. METHODS We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. RESULTS Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after > or =20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after > or =20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. CONCLUSIONS Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer.

Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes.

Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented.

First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: A meta‐analysis of epidemiological studies

BACKGROUND Several studies have evaluated maternal first trimester paroxetine use and the prevalence of congenital defects, particularly cardiac defects. To synthesize current epidemiologic information, a meta-analysis was conducted. METHODS A systematic literature search was conducted for original research published from January 1, 1992, through September 30, 2008. Results were extracted using predefined criteria, and authors were contacted for additional information when necessary. Compiled results were evaluated for funnel plot asymmetry, heterogeneity, and study characteristic associations. Where appropriate, fixed-effect summary estimates were calculated and sensitivity analyses performed. RESULTS Twenty reports (11 including results for aggregated congenital and combined cardiac defects, six for aggregated congenital defects only, and three for combined cardiac defects only) met prespecified inclusion criteria. There was little evidence of funnel plot asymmetry or overall heterogeneity. Summary estimates were produced for combined cardiac defects (prevalence odds ratio [POR], 1.46; 95% confidence interval [CI], 1.17-1.82) and aggregated congenital defects (POR, 1.24; 95% CI, 1.08-1.43) and first trimester paroxetine use. Some study characteristics may be associated with differential POR estimates for paroxetine and either combined cardiac or aggregated congenital defects. CONCLUSIONS This meta-analysis found little evidence of publication bias or overall statistical heterogeneity and only weak evidence of associations with some study characteristics. Although subject to limitations, the summary estimate indicates an increased prevalence of combined cardiac defects with first trimester paroxetine use. The summary estimate also indicates an increased prevalence of aggregated congenital defects with paroxetine; however, this association may be explained, in part, by the increased prevalence of combined cardiac defects.

Exploring the genetic basis of chronic periodontitis: a genome-wide association study

Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss. Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (ARIC) Study (mean age—62 years, moderate CP—43% and severe CP—17%). We detected no genome-wide significant association signals for CP; however, we found suggestive evidence of association (P < 5 × 10−6) for six loci, including NIN, NPY, WNT5A for severe CP and NCR2, EMR1, 10p15 for moderate CP. Three of these loci had concordant effect size and direction in an independent sample of 656 adult EA participants of the Health, Aging, and Body Composition (Health ABC) Study. Meta-analysis pooled estimates were severe CP (n = 958 versus health: n = 1909)—NPY, rs2521634 [G]: odds ratio [OR = 1.49 (95% confidence interval (CI = 1.28–1.73, P = 3.5 × 10−7))]; moderate CP (n = 2293)—NCR2, rs7762544 [G]: OR = 1.40 (95% CI = 1.24–1.59, P = 7.5 × 10−8), EMR1, rs3826782 [A]: OR = 2.01 (95% CI = 1.52–2.65, P = 8.2 × 10−7). Canonical pathway analysis indicated significant enrichment of nervous system signaling, cellular immune response and cytokine signaling pathways. A significant interaction of NUAK1 (rs11112872, interaction P = 2.9 × 10−9) with smoking in ARIC was not replicated in Health ABC, although estimates of heritable variance in severe CP explained by all single nucleotide polymorphisms increased from 18 to 52% with the inclusion of a genome-wide interaction term with smoking. These genome-wide association results provide information on multiple candidate regions and pathways for interrogation in future genetic studies of CP.

A review: Obesity and screening for breast, cervical, and colorectal cancer in women

The literature examining obesity as a barrier to screening for breast, cervical, and colorectal cancer has not been evaluated systematically. With the increasing prevalence of obesity and its impact on cancer incidence and mortality, it is important to determine whether obesity is a barrier to screening so that cancers among women at increased risk because of their body size can be detected early or prevented entirely. On the basis of 32 relevant published studies (10 breast cancer studies, 14 cervical cancer studies, and 8 colorectal cancer studies), the authors reviewed the literature regarding associations between obesity and recommended screening tests for these cancer sites among women in the U.S. The most consistent associations between obesity and screening behavior were observed for cervical cancer. Most studies reported an inverse relation between decreased cervical cancer screening and increasing body size, and several studies reported that the association was more consistent among white women than among black women. For breast cancer, obesity was associated with decreased screening behavior among white women but not among black women. The literature regarding obesity and colorectal cancer screening adherence was mixed, with some studies reporting an inverse effect of body size on screening behavior and others reporting no effect. Overall, the results indicated that obesity most likely is a barrier to screening for breast and cervical cancers, particularly among white women; the evidence for colorectal cancer screening was inconclusive. Thus, efforts to identify barriers and increase screening for breast and cervical cancers may be targeted toward obese women, whereas outreach to all women should remain the objective for colorectal cancer screening programs. Cancer 2008.