Cancer Causes & Control

To examine if survival has changed over the last 20 years in patients with base of tongue and tonsil cancers in the United States. Using SEER data, we employed Kaplan–Meier method to draw survival curves and calculate survival rates, and estimated adjusted hazard ratios (HR). From the 1980s to the 2000s, the 5-year overall survival rates statistically significantly improved by 100% from 25 to 51% among patients with one primary base of tongue cancer and 28–60% among those with one primary tonsil cancer (p values for trend <0.001). In addition, the 5-year cancer-specific survival improved by 222.4 and 276%, respectively, among two types of patients. Survival improvement was more pronounced among male patients than among female patients regardless of young or old age, while the improvement was generally consistent among patients with different tumor stages and treatment methods. In contrast, however, those patients with subsequent multiple cancers showed no improvement in overall survival over time. The survival of patients with base of tongue and tonsil cancer has significantly improved over the last decades in the United States. Whether the improvement is associated with HPV infection, screening, or early detection is worthy to study in future.

Genetic predisposition plays a major role in the etiology of melanoma, but known genetic markers only account for a limited fraction of family-history-associated melanoma cases. Expression microarrays have offered the opportunity to identify further genomic profiles correlated with family history of melanoma. We aimed to distinguish mRNA expression signatures between melanoma cases with and without a family history of melanoma. Based on the Nurses’ Health Study, family history was defined as having one or more first-degree family members diagnosed with melanoma. Melanoma diagnosis was confirmed by reviewing pathology reports, and tumor blocks were collected by mail from across the USA. Genomic interrogation was accomplished through evaluating expression profiling of formalin-fixed paraffin-embedded tissues from 78 primary cutaneous invasive melanoma cases, on either a 6K or whole-genome (24K) Illumina gene chip. Gene set enrichment analysis was performed for each batch to determine the differentially enriched pathways and key contributing genes. The CXC chemokine receptor 4 (CXCR4) pathway was consistently up-regulated within cases of familial melanoma in both platforms. Leading edge analysis showed four genes from the CXCR4 pathway, including MAPK1, PLCG1, CRK, and PTK2, were among the core members that contributed to the enrichment of this pathway. There was no association between the enrichment of CXCR4 pathway and NRAS, BRAF mutation, or Breslow thickness of the primary melanoma cases. We found that the CXCR4 pathway might constitute a novel susceptibility pathway associated with family history of melanoma in first-degree relatives.

Use of recommended screening tests can reduce new colorectal cancers (CRC) and deaths, but screening uptake is suboptimal in the United States (U.S.). The Centers for Disease Control and Prevention (CDC) funded a second round of the Colorectal Cancer Control Program (CRCCP) in 2015 to increase screening rates among individuals aged 50–75 years. The 30 state, university, and tribal awardees supported by the CRCCP implement a range of multicomponent interventions targeting health systems that have low CRC screening uptake, including low-income and minority populations. CDC invited a select subset of 16 CRCCP awardees to form a learning laboratory with the goal of performing targeted evaluations to identify optimal approaches to scale-up interventions to increase uptake of CRC screening among vulnerable populations. This commentary provides an overview of the CRCCP learning laboratory, presents findings from the implementation of multicomponent interventions at four FQHCs participating in the learning laboratory, and summarizes key lessons learned on intervention implementation approaches. Lessons learned can support future program implementation to ensure scalability and sustainability of the interventions as well as guide future implementation science and evaluation studies conducted by the CRCCP learning laboratory.

Test the hypothesis that puerperal mastitis may alter immunity related to the mucin (MUC) family of glycoproteins and lower risk of ovarian cancer. In two case–control studies conducted in New England between 1998 and 2008, we examined the association between self-reported mastitis and ovarian cancer in 1,483 women with epithelial ovarian cancer and 1,578 controls. IgG1 antibodies against (MUC1) CA15.3 and (MUC16) CA125 were measured using electrochemiluminescence assays in a subset of controls (n = 200). Preoperative CA125 was recorded in 649 cases. The association between ovarian cancer and mastitis was assessed using unconditional logistic regression to calculate adjusted odds ratios, OR, and 95 % confidence intervals (CI). Associations between mastitis and anti-CA15.3 and anti-CA125 antibodies and preoperative CA125 levels were evaluated using adjusted linear regression models. Prior mastitis was associated with a significantly lower risk of ovarian cancer: OR (and 95 % CI) of 0.67 (0.48, 0.94) adjusted for parity, breastfeeding, and other potential confounders. The association was strongest with 2 or more episodes of mastitis, and risk declined progressively with increasing number of children and episodes of mastitis. Among controls, prior mastitis was associated with significantly higher anti-CA15.3 and anti-CA125 antibody levels and, among cases, with significantly lower preoperative CA125 levels. Puerperal mastitis may produce long-lasting anti-mucin antibodies that may lower the risk of ovarian cancer, plausibly through enhanced immune surveillance. Studying immune reactions related to MUC1 and MUC16 in the 10–20 % of breastfeeding women who develop mastitis may suggest ways to duplicate its effects through vaccines based on both antigens.

Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods, and resources from epidemiology, pathology, biostatistics, bioinformatics, and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: (1) the development of new statistical methods to address etiologic heterogeneity; (2) the enhancement of causal inference; (3) the identification of previously unknown exposure-subtype disease associations; and (4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana–Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields.

Women with a breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) mutation are at increased risk for developing breast and ovarian cancer. Various reproductive and hormonal factors have been shown to modify the risk of breast cancer. These studies suggest that estrogen exposure and deprivation are important in the etiology of hereditary cancer. Many patients are interested in the possibility of an adverse effect of fertility treatment on breast cancer risk. It is important to evaluate whether or not infertility per se or exposure to fertility medications increase the risk of breast cancer in genetically predisposed women. We conducted a matched case–control study of 1,380 pairs of women with a BRCA1 or BRCA2 mutation to determine if a history of infertility, the use of fertility medications, or undergoing in vitro fertilization (IVF) were associated with and increased the risk of breast cancer. Sixteen percent of the study subjects reported having experienced a fertility problem and 4% had used a fertility medication. Women who had used a fertility medication were not at significantly increased risk of breast cancer (odds ratio [OR] = 1.21; 95% confidence interval [CI] = 0.81–1.82) compared to non-users. Furthermore, there was no risk associated with a history of use of a fertility medication when the subjects were stratified by parity: (OR = 1.29; 95% CI = 0.83–2.01 for nulliparous women and OR = 0.81; 95% CI = 0.30–2.22 for parous women). The results of this study suggest that the use of fertility medications does not adversely affect the risk of breast cancer among BRCA mutation carriers. Given the small sizes of the exposed subgroups, these findings should be interpreted with caution and confirmatory studies are required.

Papanicolaou (Pap) testing has dramatically decreased cervical cancer incidence in the USA, but only 83 % of women screen according to guidelines. Our study aimed to examine the real-world effectiveness of various outreach methods in engaging patients who are overdue for cervical cancer screening. In total, 1,100 patients at an urban federally qualified health center overdue for Pap testing were randomized to receive usual care (control), letter outreach, email outreach, telephone outreach, or multimodal (letter/email/telephone) outreach over a period of 3 months. Eighteen months after randomization, medical records were used to determine whether and when each patient had obtained a Pap. Compared to patients receiving usual care, patients in the multimodal (36 vs. 21 %, AOR 2.3, 95 % CI 1.4, 3.6) and telephone (29 vs. 21 %, AOR 1.7, 95 % CI 1.1, 2.8) outreach groups were significantly more likely to receive cervical cancer screening during the follow-up period. Intervention effects were similar among older and younger patients. Telephone, multimodal, and letter outreach resulted in significantly lower median time to screening among patients who did screen (119, 122, and 157 days, respectively) in those groups as compared to the usual care group (270 days). This is the first study to perform a direct, randomized comparison of four distinct cervical cancer outreach intervention modalities with a control usual care group, ensuring comparability across intervention methods. In an urban primary care setting, a multimodal outreach strategy was most effective at increasing the proportion of overdue patients who undergo cervical screening and decreasing time to screening. ClinicalTrials.gov ; Registration Number: NCT02427399; https://clinicaltrials.gov/ct2/show/NCT02427399 .

Sun exposure is associated with risk of several chronic diseases including cancer. The study aim is to investigate whether sun behaviors are related to other lifestyle risk factors of cancer. We analyzed data collected in 2003–2004 by self-completed questionnaire from 34,402 Swedish women aged 40–61 years, who comprised 70% of a cohort of originally recruited from a population registry in 1991–1992 (n = 49,259). Participants were asked about annual number of sunburns and annual number of weeks of swimming and sunbathing during 1991–2002, solarium use during 1991–1998 and current sunscreen use. Compared to non-drinkers, the prevalence ratio (95% CI) in women who drank >10 g of alcohol per day was 1.64 (1.49, 1.81) for having >1 sunburn per year, 1.39 (1.29, 1.51) for swimming and sunbathing >2.5 weeks per year and 1.55 (1.41, 1.70) for using a solarium >1 time per 2 months, adjusting for demographic and lifestyle variables. Tobacco smokers were less likely to report sunburn and to use sunscreen, and more likely to sunbath and use solaria, compared with non-smokers. Physical activity was associated positively with swimming and sunbathing, and with the separate use of solaria and sunscreens, but not with number of sunburns. The lifestyle variables that explained most of the variation in sun behavior were alcohol and smoking. Our results suggest that alcohol consumption and tobacco smoking are potential lifestyle confounders which should be adjusted in studies investigating the association that sun and/or solarium exposure may have with risk of several cancer sites.