Economic and clinical burden of managing transfusion-dependent β-thalassemia in the United States.

Aims: To describe clinical complications, treatment use, healthcare resource utilization (HCRU), and costs among patients with transfusion-dependent β-thalassemia (TDT) in the United States.

Materials And Methods: Merative MarketScan Databases were used to identify patients with β-thalassemia between 1 March 2010, and 1 March 2019. Patients were eligible for inclusion with ≥1 inpatient claim or ≥2 outpatient claims for β-thalassemia and ≥8 red blood cell transfusions (RBCTs) during any 12-month period after and including the date of the first qualifying β-thalassemia diagnosis code.

Economic and Clinical Burden of Managing Sickle Cell Disease with Recurrent Vaso-Occlusive Crises in the United States.

Introduction: The aim of this study was to describe the clinical complications, treatment use, healthcare resource utilization (HCRU), and costs among patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) in the US.

Methods: Merative MarketScan Databases were used to identify patients with SCD with recurrent VOCs from March 1, 2010, to March 1, 2019. Inclusion criteria were ≥ 1 inpatient or  ≥ 2 outpatient claims for SCD and ≥ 2 VOCs per year in any 2 consecutive years after the first qualifying SCD diagnosis.

Sun exposure, vitamin D receptor genetic variants, and risk of breast cancer in the Agricultural Health Study.

Background: Epidemiologic evidence suggests a negative relation between sunlight exposure and breast cancer risk. The hypothesized mechanism is sunlight-induced cutaneous synthesis of vitamin D.

Objectives: Our goal was to examine sun exposure and its interaction with vitamin D receptor (VDR) gene variants on breast cancer risk.

Vitamin D receptor gene haplotypes and polymorphisms and risk of breast cancer: a nested case-control study.

Background: Observational and experimental studies suggest that vitamin D may influence breast cancer etiology. Most known effects of vitamin D are mediated via the vitamin D receptor (VDR). Few polymorphisms in the VDR gene have been well studied in relation to breast cancer risk and results have been inconsistent.

Evaluation of the clonal origin of multiple primary melanomas using molecular profiling.

Numerous investigations have been conducted using molecular profiling to evaluate the possible clonal origin of second malignancies in various cancer types. However, to date no study assessing clonality of multiple primaries has been conducted in melanoma. In this investigation using patients treated at a specialist melanoma treatment center, we compared the somatic mutational profiles of pairs of melanomas designated as independent on the basis of thorough assessment of their clinical and pathologic characteristics.

Sun protection and skin self-examination in melanoma survivors.

Objectives: Patients diagnosed with melanoma are at risk for developing recurrent and second primary disease. Skin self-examination (SSE) and sun protection are standard clinical recommendations to minimize risk. In this study we examined performance of these behaviors in individuals with melanoma drawn from the general population.

DNA damage and repair capacity in patients with lung cancer: prediction of multiple primary tumors.

Purpose: Patients who survive one occurrence of non-small-cell lung cancer (NSCLC) are at higher risk of a second malignancy. Capacity to repair damaged DNA may modulate individual susceptibility to develop lung cancer. Therefore, we evaluated constitutive and induced DNA damage, and repair capacity, in patients with multiple NSCLCs (cases) and compared the results to those obtained in patients with a single NSCLC (controls).

Use of anti-inflammatory drugs and lower esophageal sphincter-relaxing drugs and risk of esophageal and gastric cancers.

Background & Aims: The incidence of esophageal and gastric cardia adenocarcinoma has increased in Western countries in recent decades for largely unknown reasons. We investigated whether use of LES-relaxing drugs was related to an increased risk of esophageal and gastric cardia adenocarcinoma, and whether use of NSAIDs was related to a reduced risk of esophageal and gastric cancers.

Methods: We examined these associations by using administrative databases in a case-control study in 2 integrated health care delivery systems.

CDKN2A germline mutations in individuals with cutaneous malignant melanoma.

Cyclin-dependent kinase inhibitor type 2A (CDKN2A) has been identified as a major melanoma susceptibility gene based on the presence of germline mutations in high-risk melanoma families. In this study, we sought to identify and characterize the spectrum of CDKN2A mutations affecting p16 inhibitor of cyclin-dependent kinase type 4 (INK4a) in individuals with melanoma using a population-based study design. DNA samples from 1189 individuals with incident multiple primary melanoma (MPM) and 2424 with incident single primary melanoma unselected for family history of melanoma were available for screening of CDKN2A (p16INK4a) mutations.

Ambient UV, personal sun exposure and risk of multiple primary melanomas.

Objective: Sun exposure is the main cause of melanoma in populations of European origin. No previous study has examined the effect of sun exposure on risk of multiple primary melanomas compared with people who have one melanoma.

Methods: We identified and enrolled 2,023 people with a first primary melanoma (controls) and 1,125 with multiple primary melanomas (cases) in seven centers in four countries, recorded their residential history to assign ambient UV and interviewed them about their sun exposure.

Population-based study of natural variation in the melanocortin-1 receptor gene and melanoma.

Natural variation in the coding region of the melanocortin-1 receptor (MC1R) gene is associated with constitutive pigmentation phenotypes and development of melanoma and nonmelanoma skin cancers. We investigated the effect of MC1R variants on melanoma using a large, international population-based study design with complete determination of all MC1R coding region variants. Direct sequencing was completed for 2,202 subjects with a single primary melanoma (controls) and 1,099 subjects with second or higher-order primary melanomas (cases) from Australia, the United States, Canada, and Italy.

The prevalence of CDKN2A germ-line mutations and relative risk for cutaneous malignant melanoma: an international population-based study.

Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which "cases" have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and "controls" have incident first primary melanoma [single primary melanoma (SPM)].

A design for cancer case-control studies using only incident cases: experience with the GEM study of melanoma.

Background: The population-based case-control study is not suited to the evaluation of rare genetic (or environmental) factors. The use of a novel case-control design in which cases have second primaries and controls are cancer survivors has been proposed for this purpose.

Methods: We report results from an international study of melanoma that involved population-based ascertainment of incident cases of second or subsequent primary melanoma as the 'case' group and incident cases of first primary melanoma as the 'control' group.

Skin cancer risk discussions in melanoma-affected families.

Background: First-degree relatives (FDRs) of melanoma patients are at increased melanoma risk and thus represent an important target for prevention education. Family skin cancer risk discussions may be a useful education context.

Methods: We assessed melanoma patients' (N = 115) self-reported family skin cancer risk discussions and changes in FDRs' prevention strategies.

Polymorphisms in nucleotide excision repair genes and risk of multiple primary melanoma: the Genes Environment and Melanoma Study.

Polymorphisms in six genes involved in nucleotide excision repair of DNA were examined in a large population-based case-control study of melanoma. Genotyping was conducted for 2485 patients with a single primary melanoma (controls) and 1238 patients with second or higher order primary melanomas (cases). Patients were ascertained from nine geographic regions in Australia, Canada, Italy and the United States.

Familial aggregation of melanoma risks in a large population-based sample of melanoma cases.

Objective: Melanoma has been shown in numerous studies to be associated with sun exposure, and with host phenotypic factors of genetic origin. In this study we use information from a large series of incident cases of melanoma from an international population-based study to examine the patterns of incidence of melanoma in the first-degree relatives of these cases.

Methods: A total of 2508 incident cases of melanoma provided information on basic demographic data and pigmentary characteristics, in addition to detailed information on family history of melanoma.

Cutaneous desmoplastic melanoma: reappraisal of morphologic heterogeneity and prognostic factors.

Desmoplastic melanoma (DM) is a variant of melanoma, which may be confused with nonmelanocytic benign or malignant spindle cell proliferations. The histologic hallmark of DM is the presence of fusiform melanocytes dispersed in a prominent collagenous stroma. Phenotypic heterogeneity of DM is underrecognized.