Incomplete overlapping of biological, clinical, and environmental information in molecular epidemiological studies: a variety of causes and a cascade of consequences

Past medical conditions and K-ras mutations in pancreatic ductal adenocarcinoma: a hypothesis-generating study

“…This approach has limitations as compared to studies specifically designed to assess only a few medical conditions, and with respect to prospective studies. The latter, however, have often been unable to avoid selection biases caused by low retrieval of tumor specimens [20,49]. Indeed, PDA is the tumor with the lowest histo-cytological confirmation rate, and an increasing proportion of patients is diagnosed using cytology rather than histology, partly because of the low resectability rate [50].…”

Estimating dietary intakes from a brief questionnaire: A simulation study of reliability in a molecular epidemiologic study of pancreatic and biliary diseases

“…While more detailed intake assessments are ideal, in studies where the use of brief dietary assessment methods is warranted to maximize participation, external sources of information and methods such as those used here may provide insights on the likely reliability of estimated intakes. In turn, this approach may constitute an efficient way to initially explore new and complex hypotheses, and to suggest which results may be worth pursuing with in-depth dietary questionnaires by subsequent studies [2,3,25]. Therefore, a role exists for simpler tools to improve the present state of knowledge on the role of diet in the etiology of pancreatic and biliary diseases.…”

“…Furthermore, a particularly delicate balance must often be achieved by molecular and genetic epidemiologic studies: while interviews to subjects must elicit information on a broad range of exposures hypothesised to interact among themselves, with gene products and with other biological targets, unbiased data are also required on a variety of clinical and biological cofactors or intermediate endpoints. Incomplete overlapping of biological, clinical and environmental information is hence a common source of limitations to both internal and external validity, specially in studies on geneenvironment interactions conducted on severely ill patients [1][2][3][4] Restrictions in the scope of factors assessed in the interviews may be acceptable only if they do not compromise the biological coherence of the hypotheses. Furthermore, the latter are often of high scientific risk: innovative or fully untested, complex, and exploratory [2,3].…”

“…Incomplete overlapping of biological, clinical and environmental information is hence a common source of limitations to both internal and external validity, specially in studies on geneenvironment interactions conducted on severely ill patients [1][2][3][4] Restrictions in the scope of factors assessed in the interviews may be acceptable only if they do not compromise the biological coherence of the hypotheses. Furthermore, the latter are often of high scientific risk: innovative or fully untested, complex, and exploratory [2,3]. A persuasive example is provided by studies aiming to unveil environmental influences on acquired genetic alterations in rapidly fatal diseases: they must integrate information on genetic factors, past diseases, occupations, and lifestyle factors, including diet [4][5][6][7][8].…”

“Omics” research, monetization of intellectual property and fragmentation of knowledge: can clinical epidemiology strengthen integrative research?

“…No valid and clinically or socially meaningful ''marker research'' is ever possible with only ''specimens'': we study human beings, people with specific, usually complex diseases; we may thus need valid information on signs and symptoms of the disease, help-seeking pathways, self-care practices, results of exploratory and diagnostic procedures, measures of disease stage and progression, or information on potential confounders and effect modifiers [5,8e10]. In addition to Ransohoff's well-placed emphasis on access to biological specimens [18], we believe more emphasis is needed on the importance of access to the corresponding clinical information and, sometimes, to lifestyle and environmental information too [35,36]. The fact that a low percentage of eligible cases is analyzed may partly be due to the a priori, willing exclusion of large sections of patients, by design; for instance, in some studies on pancreatic cancer, patients without surgical tumor material were excluded, even though up to two thirds of eligible patients fell into such category [36].…”