Risk of malignancy in first-degree relatives of patients with pancreatic carcinoma

Department of Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Cancer (Impact Factor: 4.89). 07/2005; 104(2):388-94. DOI: 10.1002/cncr.21166
Source: PubMed


Approximately 5-10% of pancreatic carcinoma (PC) patients report a family history of the disease. In some families, mutations of tumor suppressor genes have been elucidated, but for most the causative gene remains unidentified. Counseling the families of PC patients regarding their risk of cancer remains problematic because little information is available.
The authors analyzed family history questionnaires completed by 426 unselected, sequential Mayo Clinic patients with PC. The prevalence of malignancy reported among 3355 of their first-degree relatives was compared with the Surveillance, Epidemiology, and End Results Project (SEER) 9 (2000) registry. Age-adjusted and gender-adjusted standardized incidence ratios (SIRs) were generated.
Greater than 130,000 person-years at risk for cancer among the first-degree relatives were analyzed. The risk of PC was found to be increased among the first-degree relatives of patients with PC (SIR of 1.88; 95% confidence interval [95% CI], 1.27-2.68), as was the risk of liver carcinoma (SIR of 2.70; 95% CI, 1.51-4.46). Lymphoma (SIR of 0.28; 95% CI, 0.12-0.55), bladder carcinoma (SIR of 0.55; 95% CI, 0.31-0.89), breast carcinoma (SIR of 0.73; 95% CI, 0.57-0.92), lung carcinoma (SIR of 0.62; 95% CI, 0.47-0.80), and prostate carcinoma (SIR of 0.71; 95% CI, 0.54-0.92) were found to be underrepresented. When the proband was age < 60 years, the risk of PC to first-degree relatives was found to be increased further (SIR of 2.86; 95% CI, 1.15-5.89). In this subgroup, no other malignancies were found to be significantly increased, although the risks of melanoma (SIR of 1.73; 95% CI, 0.70-3.57), ovarian carcinoma (SIR of 2.20; 95% CI, 0.72-5.12), and colon carcinoma (SIR of 1.37; 95% CI, 0.80-2.19) were suggestive.
There was a nearly twofold increased risk of PC in the first-degree relatives of PC probands. This risk was found to increase nearly threefold when patients were diagnosed before age 60 years. At the current time, in the absence of a pedigree suggestive of known familial cancer syndromes, the current study results do not support targeted screening for other malignancies in the first-degree relatives of patients with sporadic PC.

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Available from: Mariza Andrade, Oct 14, 2014
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    • "These low penetrant genes which by themselves have small relative risks, by virtue of being common in the population may have large population, attributable risks [10]. It has been observed from epidemiological studies that the first-degree relatives of sporadic cancer patients have a 2-3-fold higher risk of developing cancer at the same site and this has also been described for pancreatic cancer but in only retrospective studies [10] [11] [12]. Familial clustering observed in certain sporadic cancers without obvious Mendelian inheritance suggests that there is a genetic component in addition to environmental factors [13]. "
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    ABSTRACT: Aim. To examine interaction between history of cancer in first-degree relatives and tobacco smoking in index patients of pancreatic adenocarcinoma. Methods. We carried out a case-control involving 113 patients with pancreatic adenocarcinoma and 110 controls over a 12-month period at the Freeman Hospital, Newcastle upon Tyne, UK. They were all administered a detailed tobacco exposure questionnaire and a family history questionnaire. We calculated cumulative tobacco exposure and risk for pancreas cancer. Results. Both smokers (OR 3.01 (95% CI: 1.73 to 5.24)) and those with a family history of malignancy (OR 1.98 (95% CI: 1.15–3.38)) were more likely to develop pancreatic cancer. Having more than one first-degree relative with cancer did not significantly further increase the risk of pancreatic cancer. Amongst pancreatic cancer cases, cumulative tobacco exposure was significantly decreased (P = .032) in the group of smokers (current and ex-smokers) who had a family history of malignancy [mean (SD): 30.00 (24.77) pack-years versus 44.69 (28.47) pack-years with no such history]. Conclusions. Individuals with a family history of malignancy are at an increased risk of pancreatic cancer. Furthermore, individuals with a family history of malignancy and who smoke appear to require a lesser degree of tobacco exposure for the development of pancreatic cancer.
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    • "Familial aggregation of pancreatic tumours E Hiripi et al 1794 British Journal of Cancer (2009) 101(10), 1792 – 1797 & 2009 Cancer Research UK pancreatic cancer risk among spouses of pancreatic cancer patients (Hemminki and Jiang, 2002). In agreement with previous studies, our analysis confirmed an increased risk of pancreatic cancer among individuals with a family history of pancreatic cancer (Hemminki and Li, 2003a; McWilliams et al, 2005). The fact that the risk of pancreatic cancer associated with sibling history was higher might indicate a recessive mode of inheritance. "
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    • "Pancreatic cancer is more common in men (male:female ratio 1.3:1) and is unusual before the age of 45 years but the incidence rises sharply thereafter, reaching a peak in the mid to late 70s. The majority of cases have no obvious genetic predisposition but 5–10% of patients have a first-degree relative with the disease, suggesting some form of familial aggregation (McWilliams et al. 2005; McFaul et al. 2006). The risk of developing pancreatic cancer is increased in a number of familial cancer syndromes (Vitone et al. 2006); for example, the lifetime risk in Peutz-Jegher syndrome approaches 36% (Giardiello et al. 2000; Latchford et al. 2006). "
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