Risk of Other Cancers in Individuals with a Family History of Pancreas Cancer

Coté, Michele L.; Schenk, Maryjean; Schwartz, Ann G.; Vigneau, Fawn D.; Kinnard, Margaret; Greenson, Joel K.; Fryzek, Jon P.; Ying, Gui Shuang; Garabrant, David H.

doi:10.1007/s12029-008-9022-2

Cited by 10 publications

(6 citation statements)

References 40 publications

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“…Although the percentage of MEN-1 patients was low - that is, around 6% in these 2 cohorts [10,11] and not specified in another [17], since the reported ORs are based on the entire populations - it remains unclear as to what extent MEN-1 has influenced the pooled ORs of the present meta-analysis. At any rate, the increased risk of developing PNET in individuals with a first-degree family history of other cancers might be related to unknown genetic factors, or to shared environmental factors, and this finding reflects current knowledge with regard to other tumor types [19,20]. …”

Section: Discussionsupporting

confidence: 60%

Diabetes, Smoking, Alcohol Use, and Family History of Cancer as Risk Factors for Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis

et al. 2015

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Background and Aims: Risk factors for pancreatic neuroendocrine tumors (PNETs) are not well understood. The aim of this systematic review was to assess if diabetes mellitus, smoking, alcohol use, and family history of cancer are risk factors for PNETs. Methods: MEDLINE and abstracts from the European and North American Neuroendocrine Tumor Societies (ENETS and NANETS) were searched for studies published until October 2013. Eligible studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Five studies evaluating 4 individual populations were included (study accrual period 2000-2011) into the meta-analysis, involving 827 cases (range 160-309 per study) and 2,407 controls (range 233-924 per study). All studies had a case-control design and described regional series. The pooled adjusted odds ratio was 2.74 (95% CI: 1.63-4.62; p < 0.01; I² = 60.4%) for history of diabetes, 1.21 (95% CI: 0.92-1.58; p = 0.18; I² = 45.8%) for ever smoking, 1.37 (95% CI: 0.99-1.91; p = 0.06; I² = 0.0%) for heavy smoking, 1.09 (95% CI: 0.64-1.85; p = 0.75; I² = 85.2%) for ever alcohol use, 2.72 (95% CI: 1.25-5.91; p = 0.01; I² = 57.8%) for heavy alcohol use, and 2.16 (95% CI: 1.64-2.85; p < 0.01; I² = 0.0%) for first-degree family history of cancer. Conclusions: Diabetes mellitus and first-degree family history of cancer are associated with an increased risk of sporadic PNET. There was also a trend for diagnosis of sporadic PNET associated with heavy smoking. Alcohol use may be a risk factor for PNET, but there was considerable heterogeneity in the meta-analysis. These results suggest the need for a larger, homogeneous, international study for the clarification of risk factors for the occurrence of PNET.

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Section: Discussionsupporting

confidence: 60%

Diabetes, Smoking, Alcohol Use, and Family History of Cancer as Risk Factors for Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis

et al. 2015

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“…As expected, PDAC risks were increased overall and for ATM, BRCA2, PALB2, and CDKN2A genes; however, the risks did not reach statistical significance for BRCA1 and MMR genes. In previous studies that found PDAC risk in first-degree relatives of patients with PDAC to be at least 2-fold, our study estimated that risk was increased by 4.19-fold when the proband carried a known PGV in a PDAC-associated gene. These results provide useful risk estimates that should encourage genetic risk assessment and counseling of family members in the context of cascade genetic testing.…”

Section: Discussionmentioning

confidence: 99%

“…Besides PDAC, first-degree relatives of patients with PDAC are susceptible to other cancers, especially those associated with cancer syndromes that include PDAC. For example, in a study with 247 patients and 1816 first-degree relatives, lymphoma and breast cancer risks were 2-fold higher among relatives with a family history of PDAC. Considering both family history and susceptibility genes, a previous study by our research team found that when a patient with PDAC was positive for an aggregate of susceptibility variants, risks for ovarian and breast cancers were significantly higher for their first-degree relatives as was primary liver cancer risk among their female first-degree relatives.…”

Section: Introductionmentioning

confidence: 99%

Risk of Syndrome-Associated Cancers Among First-Degree Relatives of Patients With Pancreatic Ductal Adenocarcinoma With Pathogenic or Likely Pathogenic Germline Variants

et al. 2023

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ImportanceIncreased cancer risk in first-degree relatives of probands with pancreatic ductal adenocarcinoma (PDAC probands) who carry pathogenic or likely pathogenic germline variants (PGVs) in cancer syndrome–associated genes encourages cascade genetic testing. To date, unbiased risk estimates for the development of cancers on a gene-specific basis have not been assessed.ObjectiveTo quantify the risk of development of PDAC and extra-PDAC among first-degree relatives of PDAC probands who carry a PGV in 1 of 9 cancer syndrome–associated genes—ATM, BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2, and CDKN2A.Design, Setting, and ParticipantsThis case series focused on first-degree relatives of PDAC probands carrying PGVs in specific cancer syndrome–associated genes. The cohort comprised clinic-ascertained patients enrolled in the Mayo Clinic Biospecimen Resource for Pancreas Research registry with germline genetic testing. In total, 234 PDAC probands carrying PGVs were drawn from the prospective research registry of 4562 participants who had undergone genetic testing of cancer syndrome–associated genes. Demographic and cancer-related family histories were obtained by questionnaire. The data were collected from October 1, 2000, to December 31, 2021.Main Outcomes and MeasuresFor the PDAC probands, the genetic test results of the presence of PGVs in 9 cancer syndrome–associated genes were obtained by clinical testing. Cancers (ovary, breast, uterus or endometrial, colon, malignant melanoma, and pancreas) among first-degree relatives were reported by the probands. Standardized incidence ratios (SIRs) were used to estimate cancer risks among first-degree relatives of PDAC probands carrying a PGV.ResultsIn total, 1670 first-degree relatives (mean [SD] age, 58.1 [17.8] years; 853 male [51.1%]) of 234 PDAC probands (mean [SD] age, 62.5 [10.1] years; 124 male [53.0%]; 219 [94.4%] White; 225 [98.7%] non-Hispanic or non-Latino]) were included in the study. There was a significantly increased risk of ovarian cancer in female first-degree relatives of probands who had variants in BRCA1 (SIR, 9.49; 95% CI, 3.06-22.14) and BRCA2 (SIR, 3.72; 95% CI, 1.36-8.11). Breast cancer risks were higher with BRCA2 variants (SIR, 2.62; 95% CI, 1.89-3.54). The risks of uterine or endometrial cancer (SIR, 6.53; 95% CI, 2.81-12.86) and colon cancer (SIR, 5.83; 95% CI, 3.70-8.75) were increased in first-degree relatives of probands who carried Lynch syndrome mismatch repair variants. Risk of PDAC was also increased for variants in ATM (SIR, 4.53; 95% CI, 2.69-7.16), BRCA2 (SIR, 3.45; 95% CI, 1.72-6.17), CDKN2A (SIR, 7.38; 95% CI, 3.18-14.54), and PALB2 (SIR, 5.39; 95% CI, 1.45-13.79). Melanoma risk was elevated for first-degree relatives of probands with CDKN2A variants (SIR, 7.47; 95% CI, 3.97-12.77).Conclusions and RelevanceIn this case series, the presence of PGVs in 9 cancer syndrome–associated genes in PDAC probands was found to be associated with increased risk of 6 types of cancers in first-degree relatives. These gene-specific PDAC and extra-PDAC cancer risks may provide justification for clinicians to counsel first-degree relatives about the relevance and importance of genetic cascade testing, with the goal of higher uptake of testing.

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“…Both prospective and retrospective studies have found increased risks of other cancers in relatives of pancreatic cancer patients, particularly breast cancer 23,24 , melanoma 24 , ovarian 25 , and colorectal cancer 24,26 . Study from NFPTR reported an increased risk of dying from cancer of the breast (weighted standardized mortality ratio (wSMR) = 1.66 [95%CI: 1.15-2.34]), ovarian (wSMR=2.05 [95%CI: 1.10-3.49]), bile duct (wSMR = 2.89 [95%CI: 1.04-6.39] and bladder (wSMR = 1.90 [95%CI: 1.00-3.30]) in FDRs of FPC probands 27 .…”

Section: Family History and Risk Of Pancreatic Cancermentioning

confidence: 99%

Inherited pancreatic cancer

Chen¹,

Roberts²,

Klein³

2017

Chin. Clin. Oncol.

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Pancreatic cancers arise through a series of genetic events both inherited and acquired. Inherited genetic changes, both high penetrance and low penetrance, are an important component of pancreatic cancer risk, and may be used to characterize populations who will benefit from early detection. Furthermore, pancreatic cancer patients with inherited mutations may be particularly sensitive to certain targeted agents, providing an opportunity to personalized treatment. Family history of pancreatic cancer is one of the strongest risk factors for the disease, and is associated with an increased risk of caners at other sites, including but not limited to breast, ovarian and colorectal cancer. The goal of this chapter is to discuss the importance of family history of pancreatic cancer, and the known genes that account for a portion of the familial clustering of pancreatic cancer.

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Risk of Other Cancers in Individuals with a Family History of Pancreas Cancer

Cited by 10 publications

References 40 publications

Diabetes, Smoking, Alcohol Use, and Family History of Cancer as Risk Factors for Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis

Diabetes, Smoking, Alcohol Use, and Family History of Cancer as Risk Factors for Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis

Risk of Syndrome-Associated Cancers Among First-Degree Relatives of Patients With Pancreatic Ductal Adenocarcinoma With Pathogenic or Likely Pathogenic Germline Variants

Inherited pancreatic cancer

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