Malignancies In First-degree Relatives Research Articles

Identifying childhood leukemia with an excess of hematological malignancies in first-degree relatives in Brazil.

Familial aggregation in childhood leukemia is associated with epidemiological and genomic factors. Albeit epidemiological studies on the familial history of hematological malignancies (FHHMs) are scarce, genome-wide studies have identified inherited gene variants associated with leukemia risk. We revisited a dataset of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients to explore the familial aggregation of malignancies among their relatives. A series of 5,878 childhood leukemia (≤21 years of age) from the EMiLI study (2000-2019) were assessed. Lack of well-documented familial history of cancer (FHC) and 670 cases associated with genetic phenotypic syndromes were excluded. Leukemia subtypes were established according to World Health Organization recommendations. Logistic regression-derived odds ratios (ORs) and 95% confidence intervals (CIs) were performed and adjusted by age as a continuous variable, where ALL was the reference group for AML and conversely. The pedigree of 18 families with excess hematological malignancy was constructed. FHC was identified in 472 of 3,618 eligible cases (13%). Ninety-six of the 472 patients (20.3%) had an occurrence of FHHMs among relatives. Overall, FHC was significantly associated with AML (OR, 1.36; 95% CI, 1.01-1.82; p = 0.040). Regarding the first-degree relatives, the OR, 2.92 95% CI,1.57-5.42 and the adjOR, 1.16 (1.03-1.30; p0.001) were found for FHC and FHHM, respectively. Our findings confirmed that AML subtypes presented a significant association with hematological malignancies in first-degree relatives. Genomic studies are needed to identify germline mutations that significantly increase the risk of developing myeloid malignancies in Brazil.

S3539 The Importance of Taking a Family History: Diagnosis of Lynch Syndrome After Direct Access Colonoscopy

Introduction: Lynch Syndrome (LS) is a familial cancer-predisposition syndrome caused by mutations in DNA mismatch repair genes. LS accounts for 3-8% of all new cases of colorectal cancer (CRC), and it increases the lifetime risk of multiple associated cancers. LS is common, occurring in approximately 1 in 200-300 individuals, but remains underdiagnosed. Estimates indicate that less than 1% of individuals with LS are aware of their diagnosis. This represents a missed opportunity for cancer screening and prevention. Case Description/Methods: A 50-year-old healthy woman presented to endoscopy for direct access screening colonoscopy. Family history included in her electronic medical record noted two malignancies in first degree relatives (thyroid and uterine). Colonoscopy revealed 13 tubular adenomas (3- 12mm). Office follow up to discuss genetic testing was delayed due to COVID-19. 10 months later the patient presented for follow up, and family history revealed ureteral and CRC in her father, CRC in her paternal uncle, and uterine cancer in her paternal aunt and paternal grandmother. Germline genetic testing was discussed and sent. While awaiting results, she was found to have atypical endometrial cells on routine pap smear. Colposcopy revealed complex endometrial hyperplasia (CAH) with atypia, bordering on grade 1 endometrioid carcinoma. The following week, genetic results showed a mutation in MSH6. One week later, surveillance colonoscopy revealed 4 sub-cm tubular adenomas. She then underwent total hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node biopsy. Pathology showed CAH but no definitive features of endometrioid carcinoma. The patient recovered from her surgery uneventfully, is now in a screening/surveillance program, and cascade testing has begun for her first-degree relatives, including her two adult children. Discussion: This case highlights the importance of obtaining cancer family history during patient contact, so that this underdiagnosed condition can be identified and patients can benefit from appropriate cancer screening..

Familial Aggregation and Heritability of Nonmedullary Thyroid Cancer in an Asian Population: A Nationwide Cohort Study.

The purpose of this work is to assess the extent of familial aggregation of nonmedullary thyroid cancer (NMTC) and the relative risks (RRs) of chronic thyroid diseases and common malignancies in first-degree relatives of NMTC patients. In the National Health Insurance Research database of Taiwan, all eligible individuals in 2016 were analyzed (n = 23 696 659) and the family structures of 38 686 patients diagnosed with NMTC between 1997 and 2016 were identified. The prevalence and RRs of NMTC, chronic thyroid diseases, and common malignancies in individuals with first-degree relatives with NMTC were examined. The accountability of heritability and environmental factors to NMTC susceptibility was estimated using the polygenic liability model. The prevalence of NMTC was 0.16% in the general population and 0.64% in individuals with first-degree relatives with NMTC. Regarding affected relatives, the RR (95% CI) for NMTC was 20.12 (4.86-83.29) for twins, 6.43 (4.80-8.62) for siblings, 5.24 (4.55-6.03) for offspring, 5.07 (4.41-5.81) for parents, and 2.07 (1.53-2.81) for spouses. The estimated genetic, common environmental, and nonshared environmental contributions to NMTC were 28.0%, 14.3%, and 57.7%, respectively. A family history of NMTC was associated with higher risks of thyroid nodules (RR, 2.26; 95% CI, 2.18-2.35), Hashimoto thyroiditis (2.11; 1.89-2.36), Graves disease (1.49; 1.42-1.57), lung cancer (1.56; 1.32-1.85), and leukemia and lymphoma (1.24; 1.03-1.50). Our findings demonstrate the importance of genetic and environmental contributions to NMTC susceptibility and highlight the coaggregation of chronic thyroid diseases and multiple malignancies with NMTC.

No Increased Prevalence of Malignancies Among First-Degree Relatives of Patients with Chronic Myeloid Leukemia - Data from Population-Based Swedish Registries

Background:The etiology of chronic myeloid leukemia (CML) is essentially unknown with high doses of ionizing radiation being the only well established risk factor. We have recently published two large population-based studies showing an increased prevalence of other malignancies prior, as well as subsequent to a diagnosis of CML (Gunnarsson et al, Br J Haematol. 2015 Jun; 169(5): 683-8 and Gunnarsson et al, Leukemia. 2016 Jul; 30(7): 1562-7). One may therefore speculate that CML patients may have an increased congenital or acquired susceptibility to develop cancer. In the former case, one would expect an increased prevalence of malignancies among first-degree relatives (FDR) to CML patients.In a previous report based on the Swedish Cancer Registry, no increased aggregation of malignancies was detected among family members to CML patients diagnosed between 1958 and 2004 (Bjorkholm et al, Blood. 2013 Jul 18; 122(3): 460-1). However, a more strict definition of CML (requiring e.g. thepresence of a Philadelphia chromosome or the BCR/ABL fusion gene) was introduced with the updated WHO classification in 2002, making subsequently diagnosed CML cohorts more homogenous.Materials and methods:Aiming to establish the prevalence of malignancies among FDR of a large and well-defined contemporary CML cohort in Sweden compared to carefully matched controls, we have used four large Swedish population based registers.To identify Swedish patients with CML diagnosed between 2002 and 2013, we used the Swedish CML Register to which all CML patients diagnosed January 1st 2002 and later are reported. FDR were identified by use of the Swedish Multi-Generation Register, which comprises information about parent-sibling-offspring relationships of persons that has been registered in Sweden at some time since 1961 and born later than 1932.By linking this cohort to the Swedish Cancer Register, we retrieved information about malignancies for each FDR.Each CML patient was matched with five, age-, gender- and county of residence-matched controls, selected from the Swedish Total Population Register. All controls had to be alive and free of CML at the time of CML diagnosis for the matching CML patient.To calculate odds ratio (OR) and 95% confidence intervals (CI), conditional logistic regression were used.Results:In the Swedish CML register, 984 patients were identified. Among them 184 patients were excluded due to a birth year prior to 1932. Among the 800 remaining CML patients, 4 287 FDR were identified and included in the analysis (parents: 1 346, siblings: 1 497 and children: 1 444). Correspondingly, 20 930 matched controls were included in the analysis.In total, 611 malignancies were identified among the FDR of CML patients compared to 2844 in the control group yielding an OR of 1.057 (95% CI 0.962 - 1.162).Neither hematological malignancies nor solid tumors were increased in the CML-FDR group (Table 1). Notably, none of the FDRs in the CML-FDR group had a CML diagnosis.Conclusions:Using data from four large Swedish population based registers and based on the fate of more than 4 000 FDR of 800 CML patients diagnosed in the modern era of cytogenetics, as well as closely matched CML-free controls, we show that there is no familial aggregation of malignancies in FDRs of patients with CML. These results suggest that a hereditary predisposition to develop cancer is unlikely to be a part of the pathogenesis of CML. [Display omitted] DisclosuresHöglund:Akinion Pharmaceuticals: Consultancy; Janssen-Cilag: Honoraria. Lambe:AstraZeneca: Other: Stock Ownership ; Pfizer: Other: Stock Ownership . Richter:Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Ariad: Honoraria, Research Funding. Själander:ARIAD: Consultancy.

Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?

CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, <50 and ≥50 years. One thousand one hundred and sixty-seven patients with IDC and ILC entered the study. A family history of malignancies was reported in 21.6 % of patients with IDC as opposed to 37.8 % of patients with ILC (P < 0.001). A history of gastric cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P < 0.008. A family history of breast cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.

Intraductal papillary mucinous neoplasm of the pancreas: Associated cancers, family history, genetic predisposition?

High rates of extrapancreatic malignancies (EPM) have been observed in patients with intraductal papillary mucinous neoplasm (IPMN). IPMN in patients with familial pancreatic cancer have also been reported. Our purpose was to evaluate the association of IPMN with EPM, malignancies in family members, and germline BRCA1 and BRCA2 mutations. Using retrospective analysis on prospectively collected data from 82 patients with IPMN and direct contact for familial cancer history, data were compared with those of 150 patients with pancreatic ductal adenocarcinoma (PDAC). The common germline mutations in the BRCA1 and BRCA2 genes were evaluated on available IPMN patients. EPM rates were greater in IPMN than PDAC patients (P = .002). Malignancies in first-degree relatives, specifically pancreatic cancer, were more common among IPMN than PDAC patients (P = .028). IPMN patients with EPM had high rates of relatives with colorectal cancer (31%). Two of the 51 genetically tested patients (4%) were BRCA2 mutation carriers, and both had first-degree relatives with pancreatic cancer. One patient fulfilled the Amsterdam criteria for hereditary nonpolyposis colon cancer; however, the neoplasm was microsatellite stable. Our results demonstrated high rates of EPM among IPMN patients. There was an increased rate of cancer in families of IPMN patients, specifically pancreatic cancer. A high rate of colorectal cancer in families of IPMN patients who have EPM was also observed. These findings suggest a genetic component in the pathogenesis of IPMN. Possible genetic changes include BRCA2 mutations, which are found in 25% of IPMN patients with a family history of pancreatic cancer.

92 PROSTATE CANCER RISK VARIANTS ASSOCIATED WITH SUSCEPTIBILITY TO OTHER MALIGNANCIES

You have accessJournal of UrologyProstate Cancer: Basic Research I1 Apr 201092 PROSTATE CANCER RISK VARIANTS ASSOCIATED WITH SUSCEPTIBILITY TO OTHER MALIGNANCIES Brian T. Helfand, Stacy Loeb, Donghui Kan, Joshua J. Meeks, Brian Le, Matthias D. Hofer, Jessica A. Banks, Phillip R. Cooper, and William J. Catalona Brian T. HelfandBrian T. Helfand Chicago, IL More articles by this author , Stacy LoebStacy Loeb Baltimore, MD More articles by this author , Donghui KanDonghui Kan Chicago, IL More articles by this author , Joshua J. MeeksJoshua J. Meeks Chicago, IL More articles by this author , Brian LeBrian Le Chicago, IL More articles by this author , Matthias D. HoferMatthias D. Hofer Chicago, IL More articles by this author , Jessica A. BanksJessica A. Banks Chicago, IL More articles by this author , Phillip R. CooperPhillip R. Cooper Chicago, IL More articles by this author , and William J. CatalonaWilliam J. Catalona Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.141AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There are now >50 known genetic variants that contribute to prostate cancer (CaP) susceptibility. Prior studies have demonstrated associations between several of these genetic regions with breast, colorectal, and bladder cancers. However, the inter-relationship between CaP, other malignancies, and the genetic variants remains to be determined. Therefore, we investigated the association between the genetic risk variants and the risk of other malignancies in CaP patients. We also examined the relationship of genetic variants in CaP patients to the frequency of other malignancies in first-degree relatives. METHODS The genotypes of 14 CaP susceptibility variants along chromosomes 2p15, 3q21, 5p15, 8q24, 10q11, 11q13, 17q12, 17q24, 19q13.2, and Xp11 were determined for 473 patients with CaP. Statistical analysis was used to compare the frequencies of the genetic variants in patients whose only tumor was CaP to those with CaP and other malignancies. In addition, we compared the frequency of genetic variants in CaP patients with a first-degree family history of another malignancy, versus those without a family history of other cancers. RESULTS Among patients treated for CaP, 11.6%, 0.9%, and 0.6% reported a personal history of skin cancer, lymphoma/leukemia, and colon cancer, respectively. Men who were carriers of the variants along 10q11 (p=0.03) and 17q24 (p=0.008) were significantly more likely to have colon and hematologic cancers, respectively. In comparison, the variants along chromosomes 3q21 (p=0.0002) and Xp11 (p=0.04) had an inverse relationship with the development of skin cancers. The data obtained in the family history part of the study revealed carriers of the rs16901979 variant along 8q24 with CaP were significantly (p=0.02) more likely to have a first-degree relative with colon cancer. Finally, carriers of variants along 5p15 (p=0.05) and 19q13 (p=0.0008) with CaP were significantly more likely to have a first-degree relative with skin cancer. CONCLUSIONS Previous reports have implicated an increased frequency of other malignancies in CaP patients. However, the genetic mechanisms underlying these associations have remained elusive. We report an association between the CaP susceptibility variants and an increased frequency of colon cancer and hematologic malignancies, and a decreased frequency of other cancers. In addition, specific genetic variants appear to be associated with a family history of colon and skin cancers. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e38 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brian T. Helfand Chicago, IL More articles by this author Stacy Loeb Baltimore, MD More articles by this author Donghui Kan Chicago, IL More articles by this author Joshua J. Meeks Chicago, IL More articles by this author Brian Le Chicago, IL More articles by this author Matthias D. Hofer Chicago, IL More articles by this author Jessica A. Banks Chicago, IL More articles by this author Phillip R. Cooper Chicago, IL More articles by this author William J. Catalona Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Increased Risks of Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Myelofibrosis (MF) among 24577 First-Degree Relatives of 11039 Patients with Chronic Myeloproliferative Disorders (MPD) in Sweden.

Background. Familial clustering of PV, ET, MF, and chronic myeloid leukemia (CML) has been reported through case reports and smaller case series. Recently, several studies reported that in families with multiple MPD patients, the JAK2 mutation is not an early germ line predisposing factor for MPD but rather a facilitator of proliferative advantages. However, the degree of familial clustering in the population has not been defined. We have conducted the first large population-based study to quantify risks of developing MPD and related malignancies in first-degree relatives of MPD patients.Methods. Using high-quality central population-based registries, we identified 6217 PV, 2838 ET, and 1984 MF patients diagnosed in Swedish hospitals 1958–2005 (Cancer and local hospital-based registries), with linkable relatives; 43550 frequency-matched controls (Population registry); and first-degree relatives of cases (n=24577) and controls (n=99542) (Multigenerational registry). Relatives of MPD patients and controls were linked with the Cancer and local hospital-based registries to define occurrence of MPD and other related neoplasms. We used a marginal survival model to calculate relative risks (RR) and 95% confidence intervals (CI) as measures of familial aggregation.Results. Compared with controls, relatives of MPD patients had significantly increased risks of PV (RR=5.70; 95% CI 3.55–9.14), ET (RR=7.37; 95% CI 3.67–14.81), and MF (RR=3.53; 95% CI 1.59–7.85). Risks were similar when we restricted the analyses to relatives of patients with the same MPD (PV-PV, ET-ET, and MF-MF) Also, risk-estimates were virtually the same for various types of first-degree relatives (parents, siblings, offspring); the same was true when we calculated risks by age at MPD of cases (above vs. below 65 yrs), and sex of relatives. Age at diagnosis of MPD was not different for case and control relatives. Furthermore, relatives of MPD patients (vs. controls) had a borderline increased risk of CML (RR=1.86; 95% CI 0.90–3.74; p=0.07). As expected, we found excess of subsequent acute myeloid leukemia (AML) (n=271; 2.5%) and myelodysplastic syndrome (MDS) (n=27; 0.2%) among MPD patients; however, there were no increased risks of AML or MDS among relatives of MPD patients.Conclusions. In this first large population-based study including more than 11000 MPD patients and their almost 25000 linkable first-degree relatives, we found 3- to 7-fold elevated risks of developing MPDs among first-degree relatives of MPD patients. Our results support the hypothesis that there are common, strong, shared susceptibility genes that predispose to PV, ET, MF, and possibly CML.

Increased Risk of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Lymphoproliferative Tumors among 14689 First-Degree Relatives of 4488 MGUS Patients in Sweden.

Background. Evidence from multiply affected families, case-control and population-based registry studies implicate a role for genetic factors in multiple myeloma (MM). Previous studies based on small numbers have suggested excess risk of MGUS in relatives of MM patients. Aims of this large nationwide MGUS study were to quantify risks of developing MGUS and lymphoproliferative malignancies in first-degree relatives and to define characteristics of familial aggregation.Methods. We identified 4488 MGUS patients diagnosed in all major hematology/oncology outpatient units in Sweden (1967–2005), with linkable relatives. Using the population-based central Multigenerational Registry, we obtained 17628 frequency-matched controls and first-degree relatives of cases (n=14689) and controls (n=58698). Relatives of MGUS cases and controls were linked with hospital-based outpatient registries and the central Swedish Cancer Registry to define occurrence of MGUS and lymphoproliferative tumors. Measures of familial aggregation were calculated by a marginal survival model using relatives as the cohort.Results. Compared with controls, relative risk (RR) of MGUS was significantly increased (RR=2.84; 95% CI 1.45–5.57) in relatives of MGUS cases. Relatives of MGUS cases (vs. controls) also had excess risk of MM (RR=2.87; 95% CI 1.92–4.27), Waldenstrom's macroglobulinemia (WM) (RR=4.94; 95% CI 1.32–18.46), and chronic lymphocytic leukemia (CLL) (RR=2.05; 95% CI 1.22–3.43). Risk-estimates were similar for various types of first-degree relatives (parents, siblings, offspring); the same was true when we estimated risks by age at MGUS of cases (above vs. below 65 yrs), and sex of relatives. Age at onset of MGUS and lymphoproliferative tumors was virtually the same for case and control relatives. There was no increased risk (RR∼1) of NHL or HL among relatives of MGUS cases.Conclusions. Among first-degree relatives of a large nationwide MGUS cohort in Sweden, we found 2- to 3-fold elevated risks of developing MGUS, MM, WM, and CLL. These results suggest the operation of shared common germ line susceptibility genes in the pathway to MGUS and certain lymphoproliferative tumors. Better characterization of early genetic lesions mediating monoclonal plasma-cell proliferation, survival, and migration in the bone marrow microenvironment will ultimately enhance our understanding of MGUS, MM, WM, and CLL pathophysiology, provide clues to etiology, and allow identification of novel molecular targets.

Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph)

AbstractA role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR = 1.5; 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6; 95% CI = 1.1-2.3), and leukemia (OR = 1.4; 95% CI = 1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR = 2.8; 95% CI = 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR = 1.7; 95% CI = 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR = 3.0; 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology.

Family history of hematopoietic and non-hematopoietic malignancies and risk of non-Hodgkin lymphoma

Family history of hematopoietic malignancies has been linked to the risk of non-Hodgkin lymphoma (NHL). The relationship between family history of specific hematopoietic and non-hematopoietic malignancies and the risk of NHL and by NHL subtypes are unclear. We analyzed data from a population-based case-control study in Connecticut women. A total of 601 histologically confirmed NHL incident cases and 717 randomly selected controls were included in the study. Unconditional logistic regression was used to estimate the association between family cancer history and risk of NHL overall and by NHL subtypes. Compared to women who reported to have no family history of any malignancies in first-degree relatives, those who reported to have a family history of lymphoma (OR = 2.2, 95%CI: 1.1-4.5) or leukemia (OR = 2.5, 95%CI: 1.2-5.2) had an increased risk of NHL. The risk was higher among women who had a sibling with lymphoma or leukemia than those who had parents with lymphoma or leukemia. Several non-hematopoietic malignancies in first-degree relatives, including cancer of the lung (OR = 1.7, 95%CI: 1.1-2.6) in first-degree relatives, stomach (OR = 2.2, 95%CI: 0.8-5.9) and pancreas (OR = 2.6, 95%CI: 0.9-7.1) in parents, as well as liver (OR = 5.0, 95%CI: 1.0-24.6), breast (OR = 2.2, 95%CI: 1.3-3.9), cervix (OR = 7.5, 95%CI: 0.9-64.9), and ovary (OR = 3.5, 95%CI: 1.1-11.5) in siblings were also associated with an increased risk of NHL. The risk associated with a family history of malignancies in first degree-relatives appears to vary by type of first-degree relatives.

Chronic lymphocytic leukaemia: clinical-aetiological findings in 66 patients and their families

BackgroundLittle is known about the aetiology of chronic lymphocytic leukaemia (CLL). The family medical history is a "genomic tool" capturing interactions of genetic susceptibility, shared environment and common behaviours.MethodsA cohort of 66 consecutives patients with CLL (probands) was studied in a medical oncology practice (W.W.) from 1981 until 2005. A German version of the NCI medical history questionnaire for cancer aetiology was used. Familial clustering analysis was done by comparing the proportion of specific tumours in the first degree relatives of the CLL practice cohort with corresponding proportions of population-based cancer registry data.Results18 (41%) male and 5 (23%) female CLL probands had multiple malignancies, e.g. 2 meningiomas, 7 and 19 years after diagnosis of CLL. 46 (12%) first degree relatives had malignancies with an excess of CLL. Other conspicuous familial associations are CLL with malignancies of the upper GI tract (oesophagus, stomach) and of the nervous system.Conclusion1. Chronic lymphocytic leukaemia clusters in some families like any other disease. Predisposition genes should be searched. 2. Cancer prevention and early detection should be continued in CLL patients because of their longevity and high risk for multiple malignancies. 3. The overrepresentation of upper GI malignancies in first degree relatives of CLL patients calls for targeted oesophago-gastroscopy screening studies.

Increased risk of breast cancer in first-degree relatives of Crohn's disease patients: An IG-IBD study

Background Increased rates of colorectal cancer have been reported in patients with ulcerative colitis as well as with Crohn's colitis. This risk could be the result of shared genetic susceptibility and could be co-inherited rather than being just secondary to a long-standing, extensive mucosal inflammation. Aim. To assess the prevalence of all malignancies in first-degree relatives of Crohn's disease patients in order to establish whether any association exists. Patients and methods A total of 632 outpatients with a diagnosis of Crohn's disease and 632 control subjects were recruited. Information concerning the presence of malignancies was collected in 3292 first-degree relatives of Crohn's disease patients and in 3303 first-degree relatives of controls. Results Two hundred and fourteen (6.5%) subjects were found to be affected by malignancy in the first-degree relatives of Crohn's disease patients and 180 (5.5%) in the first-degree relatives of controls. Forty-seven (7.4%) of Crohn's disease patients had a first-degree relative with IBD, but none of them had cancer. The frequency of extra-intestinal malignancies was higher in first-degree relatives of Crohn's disease patients than in those of controls ( p = 0.011). Frequency of breast cancer in female relatives of Crohn's disease patients, mainly in mothers, was two-fold higher than that in controls (0.91% versus 0.42%; odds ratio = 2.16; 95% confidence interval = 1.14–4.08; p = 0.015). The presence of breast cancer showed no association with any specific phenotype of disease in Crohn's patients. Conclusions These results did not corroborate the hypothesis about a common genetic susceptibility between Crohn's disease and colorectal cancer. An unexpected finding was the more frequent occurrence of extra-digestive malignancies. The prevalence of breast cancer in first-degree relatives of Crohn's disease patients, in particular the mothers, was more than double than in those of controls. This association, if confirmed, would suggest that there may exist common genetic and/or environmental factors for Crohn's disease and breast cancer.

Malignant tumors in first-degree relatives of cancer patients aged 0-25 years (province of Trieste, Italy).

To determine whether the occurrence of first and second primary malignancies in first-degree relatives of cancer patients aged 0-25 years (probands) differed from that in the general population, a cohort study was carried out on 860 relatives of 265 probands living in the province of Trieste, Italy. During the follow-up period (median duration = 28 years, 25th-75th percentile = 20-34), the relatives developed 103 first primary cancers vs. 88.9 expected for a standardized incidence ratio (SIR) of 1.2 (p = 0.2). Significantly elevated risks were found for melanoma in the parents of probands aged 15-25 years with melanoma (SIR = 15.0, p = 0.002), for hemolymphatic malignancies in the fathers of probands aged 0-14 years with brain tumors (SIR = 13.3, p = 0.0005) and for hemolymphatic cancers in relatives as a whole of probands aged 15-25 years with lymphomas (SIR = 4.5, p = 0.01). During the follow-up period, 7 relatives with a first primary cancer had a subsequent malignancy vs. 4.2 expected for an SIR of 1.7 (p = 0.3). Our results indicate that young cancer patients per se should not to be considered as a factor that usually increases the risk of developing malignant tumors among their first-degree relatives, except when a known cancer family syndrome or predisposition is recognized.

Increased incidence of hematologic malignancies in first-degree relatives of patients with chronic lymphocytic leukemia.

Cases of leukemia in more than one family member occur rarely. Family members of patients with chronic lymphocytic leukemia (CLL) may, however, be at increased risk of hematologic malignancy. The charts of all patients with CLL (29) seen by the author from 1987 through 1989 were reviewed and living patients specifically questioned about family history of malignancy. Ten of the 29 (34%) had a first-degree relative with a hematologic malignancy. Three patients had a first-degree relative with CLL including a pair of identical twins. Two additional patients had a spouse with a lymphoid malignancy. No differences were found in serum immunoglobulin levels between those patients with a family history of hematologic neoplasia and those without. The lymphocytes of the majority of patients with a family history of hematologic neoplasia (60%) expressed kappa light chains as did those without (70%). An increased incidence of lymphoid malignancy has been reported in western Ashkenazi Jews and in particular those of Russian descent. The majority of our cases were of Jewish origin and came from Eastern Europe. Seven of 10 patients with a family history of hematologic neoplasia were from Eastern Europe. In contrast only one of three patients with CLL who had a first-degree relative with CLL was of Jewish origin.