We thank Maisonneuve and Lowenfels for the attention given to our article1 and for prompting us to further explore the role of smoking on age of pancreatic cancer (PC) diagnosis among those patients with family history of pancreatic cancer (FHPC). Indeed, as stated in their letter,2 the need for examining further the impact that smoking and FHPC have on PC onset is highly relevant and justified on the grounds of the findings reported by Rulyak et al.3 and others, showing that smoking anticipates PC development. Within the PanGenEU study, we addressed the association between FHPC and PC risk in two different study designs: a case-control and a reconstructed cohort study. We have re-examined this association by smoking status and age of PC development, to respond to the question raised. Considering a positive FHPC within the reconstructed cohort design, whereby the smoking status of the relatives was accounted for, the cumulative risk of PC was significantly higher in ever-smokers (P-value log-rank = 0.03). The mean ages at which ever- and never-smokers developed PC were 64.1 and 69.4 (P-value = 0.04), respectively. In the case-control study, PC patients with FHPC also developed PC earlier if they smoked, as compared with never-smokers (mean ages: 65.0 and 68.7, respectively; P-value = 0.04). We have already shown that smoking modifies the effect of FHPC on PC development.1 In line with this result, we have corroborated that ever-smokers with FHPC have a higher PC risk [odds ratio (OR) = 4.16; 95% confidence interval (CI): 2.39–7.65] relative to never-smokers with no family history. Interestingly, for family history of cancer (FHC) there was also a significant difference in age at PC onset between ever- and never-smokers in the case-control study (mean ages: 63.8 and 69.7, respectively; P-value = 1.12e-15). Likewise, the cumulative risk over time also differed significantly between both groups in the reconstructed cohort approach (P-value log-rank = 0.01). This finding underlines the importance of smoking and FHC also contributing to an earlier disease onset. Beyond this, there are other issues on which we would like to comment. The higher excess risk of PC in ever-smokers with FHPC has not been reported on a consistent basis. Some studies, for instance, did not support effect modification by smoking,4,5 whereas among some familial PC kindred studies, an excess PC risk among ever-smokers has been reported.3,6 Thus, although our study examined the association from two perspectives within a relatively large study population, the PC risk differences by smoking and FHPC will need to be confirmed in other studies, also considering their influence on the initiation of PC. Account has also to be taken of the fact that our study is based on FHPC and first-degree relatives. Our study supports current knowledge towards improvement of PC prevention, particularly in relation to the confluence of some major risk factors for PC: age, smoking and FHPC. FHC is another important factor to be taken into consideration. Further research is needed on these issues to provide PC prevention interventions by examining PC-associated risk patterns by these factors and their interactions with environmental and genetic factors, in large and well-designed studies. References 1 Molina-Montes E , Gomez-Rubio P , Márquez M et al. ; PanGenEU Study Investigators. Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives . Int J Epidemiol 2018 ; 47 : 473 – 83 . Google Scholar Crossref Search ADS PubMed 2 Maisonneuve P , Lowenfels AB . Variation of the age at onset of pancreatic cancer according to tobacco smoking and family history . Int J Epidemiol 2018 ; 47 : 1357 . 3 Rulyak SJ , Lowenfels AB , Maisonneuve P , Brentnall TA. Risk factors for the development of pancreatic cancer in familial pancreatic cancer kindreds . Gastroenterology 2003 ; 124 : 1292 – 99 . Google Scholar Crossref Search ADS PubMed 4 Jacobs EJ , Rodriguez C , Newton CC et al. Family history of various cancers and pancreatic cancer mortality in a large cohort . Cancer Causes Control 2009 ; 20 : 1261 – 69 . Google Scholar Crossref Search ADS PubMed 5 Jacobs EJ , Chanock SJ , Fuchs CS et al. Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan) . Int J Cancer 2010 ; 127 : 1421 – 28 . Google Scholar Crossref Search ADS PubMed 6 Klein AP , Brune K , Petersen GM et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds . Cancer Res 2004 ; 64 : 2634 – 38 . Google Scholar Crossref Search ADS PubMed © The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
International Journal of Epidemiology – Oxford University Press
Published: Aug 1, 2018
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