Association between family cancer history and risk of pancreatic cancer

PurposeFamily history of pancreatic adenocarcinoma is an established risk factor for the disease. However, associations of pancreatic cancer with other familial cancers are less clear. We analyzed data from the Queensland Pancreatic Cancer Study (QPCS), an Australian population-based case-control study, to investigate associations between family history of various cancer types and risk of pancreatic cancer.Materials and methodsOur study included 591 pancreatic cancer patients and 646 controls, all of whom self-reported the histories of cancer in their first-degree relatives. We used logistic regression to estimate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Based on our results, we conducted a systematic literature review using the Medline (OVID) database to identify articles pertaining to the association between family history of melanoma and risk of pancreatic cancer. A meta-analysis including associations in five published studies, unpublished results from a study co-author and the QPCS results was then performed using the DerSimonian and Laird random-effects model.ResultsCases were more likely than controls to report a family history of pancreatic cancer (OR 2.20, 95% CI 1.16–4.19) and melanoma (OR 1.74, 95% CI 1.03–2.95), but not of breast, ovarian, respiratory, other gastrointestinal or prostate cancer. Meta-analysis of melanoma family history and pancreatic cancer risk yielded an OR of 1.22 (95% CI 1.00–1.51).ConclusionsOur results yield further evidence of increased risk of pancreatic cancer in those with family histories of the disease. We also provide suggestive evidence of an association between family history of melanoma and risk of pancreatic cancer.     

Frequency and Characteristics of Familial Melanoma in Spain: The FAM-GEM-1 Study

Introduction

Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain.

Patients and methods

An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments.

Results

In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups.

Conclusions

Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.     

The histological type of endometrial cancer is not associated with menopause status at diagnosis

The latest evidence suggests that type 2 endometrial cancer may not be completely oestrogen-independent, indicating that the status of hormonal change may not be associated with the traditional classification of endometrial cancer, including the histological subtypes. However, this has not been investigated. Menopause is commonly considered a state of hormonal change in women. In the present study, we investigated the association of menopause with the histological types of endometrial cancer. Data on the histological type, menopause status at diagnosis, age at diagnosis, parity, body mass index (BMI), and overall survival rate from 2122 cases were collected. The difference in risk in developing type 1 or type 2 endometrial cancer between premenopausal and postmenopausal patients was 5.457%. A statistical difference in the association of menopause with the histological types between the two groups was seen in endometrioid and serous carcinoma, with a risk difference of 5.6 or 3.8%. A statistical difference in the association of menopause with parity between the groups was only seen in endometrioid and adenosquamous carcinoma, with a risk difference of 7.1 or 3.7%. However, BMI was not associated with histological type and the overall survival rate was not associated with menopause (P=0.764). We reported a relatively small difference in the association of menopause with type 1 or type 2, or the histological types of endometrial cancer. The survival rate was not associated with menopause. Our study suggests that menopause status at diagnosis was not strongly associated with the histological subtypes of endometrial cancer.     

Emerging strategies to treat rare and intractable subtypes of melanoma

Melanoma is the deadliest form of skin cancer, possessing a diverse landscape of subtypes with distinct molecular signatures and levels of aggressiveness. Although immense progress has been achieved therapeutically for patients with the most common forms of this disease, little is known of how to effectively treat patients with rarer subtypes of melanoma. These subtypes include acral lentiginous (the rarest form of cutaneous melanoma; AL), uveal, and mucosal melanomas, which display variations in distribution across (a) the world, (b) patient age‐groups, and (c) anatomic sites. Unfortunately, patients with these relatively rare subtypes of melanoma typically respond worse to therapies approved for the more common, non‐AL cutaneous melanoma and do not have effective alternatives, and thus consequently have worse overall survival rates. Achieving durable therapeutic responses in these high‐risk melanoma subtypes represents one of the greatest challenges of the field. This review aims to collate and highlight effective preclinical and/or clinical strategies against these rare forms of melanoma.     

Proton pump inhibitors on pancreatic cancer risk and survival

BackgroundHypergastrinemia may promote the development and progression of pancreatic cancer. Proton pump inhibitor (PPI) therapy is known to cause hypergastrinemia. We sought to determine the association between PPI therapy and the risk of developing pancreatic cancer as well as survival following pancreatic cancer diagnosis.MethodsWe conducted a nested case-control study and a retrospective cohort study in The Health Improvement Network (THIN), a medical records database representative of the UK population. In the case-control study, each patient with incident pancreatic cancer was matched with up to four controls based on age, sex, practice site and both duration and calendar time of follow-up using incidence density sampling. The odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer risk associated with PPI use were estimated using multivariable conditional logistic regression. The retrospective cohort study compared the survival of pancreatic cancer patients according to their PPI exposure at the time of diagnosis. The effect of PPI use on pancreatic cancer survival was assessed using a multivariable Cox regression analysis.ResultsThe case-control study included 4113 cases and 16,072 matched controls. PPI use was more prevalent in cases than controls (53% vs. 26% active users). Adjusting for diabetes, smoking, alcohol use and BMI, PPI users including both former users and active users with longer cumulative PPI use had a higher risk of pancreatic cancer compared to non-users. When assessing survival following pancreatic cancer diagnosis, only short-term, active users had a modest decrease in survival.ConclusionsLong-term PPI therapy may be associated with pancreatic cancer risk. While PPI users recently started on treatment had a slightly worse survival, this result likely is from reverse causation.     

Analytical Relationship between Family History and Genetic and Environmental risks,with Application to Female Breast Cancer

It is well established in genetic epidemiology that family history is an important indicator of familial aggregation of disease in a family. A strong genetic risk factor or an environmental risk factor with high familial correlation can result in a strong family history. In this paper, family history refers to the number of first‐degree relatives affected with the disease. Cui and Hopper (Journal of Epidemiology and Biostatistics 2001; 6 : 331–342) proposed an analytical relationship between family history and relevant genetic parameters. In this paper we expand the relationship to both genetic and environmental risk factors. We established a closed‐form formula for family history as a function of genetic and environmental parameters which include genetic and environmental relative risks, genotype frequency, prevalence and familial correlation of the environmental risk factor. The relationship is illustrated by an example of female breast cancer in Australia. For genetic and environmental relative risks less than 10, most of the female breast cancer cases occur between the age of 40 and 60 years. A higher genetic or environmental relative risk will move the peak of the distribution to a younger age. A more common disease allele or more prevalent environmental risk factor will move the peak to an older age. For a proband with breast cancer, it is most likely (with probability ≥80%) that none of her first‐degree relatives is affected with the disease. To enable the probability of having a positive family history to reach 50%, the environmental relative risks must be extremely as high as 100, the familial correlation as high as 0.8 and the prevalence as low as 0.1. For genetic risk alone, even the relative risk is as high as 100, the probability of having a positive family history can only reach about 30%. This suggests that the environmental risk factor seems to play a more important role in determining a strong family history than the genetic risk factor. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)