Population-Based Relative Risks for Lung Cancer Based on Complete Family History of Lung Cancer

IntroductionPublished risk estimates for diagnosis of lung cancer based on family history are typically focused on close relatives, rather than a more diverse or complete family history. This study provides estimates of relative risk (RR) for lung cancer based on comprehensive family history data obtained from a statewide cancer registry linked to a high-quality genealogy data resource that is extensive and deep. The risk estimates presented avoid common recall, recruitment, ascertainment biases, and are based on an individual’s (proband’s) lung cancer family history constellation (pattern of lung cancer affected relatives); numerous constellations are explored.MethodsWe used a population-based genealogic resource linked to a statewide electronic Surveillance Epidemiology and End Results program cancer registry to estimate RR for lung cancer for an individual based on their lung cancer family history. The family history data available for a proband included degree of relationship (first- to third-degree), paternal or maternal family lung cancer history, number of lung cancer–affected relatives, and age at diagnosis of affected relatives. More than 1.3 million probands with specific constellations of lung cancer were analyzed. To estimate RRs for lung cancer, the observed number of lung cancer cases among probands with a specific family history constellation was compared to the expected number using internal cohort-specific rates.ResultsA total of 5048 lung cancer cases were identified. Significantly elevated RR was observed for any number of lung cancer–affected relatives among first-, second-, or third-degree relatives. RRs for lung cancer were significantly elevated for each additional lung cancer first-degree relative (FDR) ranging from RR = 2.57 (confidence interval [CI] 95%: 2.39, 2.76) for 1 or more FDR to RR = 4.24 (CI 95%: 1.56, 9.23) for 3 or more FDRs affected. In an absence of FDR family history, increased risk for lung cancer was significant for increasing numbers of affected second-degree relatives (SDRs) ranging from 1.41 (CI 95%: 1.30, 1.52) for 1 or more SDRs to 4.76 (CI 95%: 1.55, 11.11) for 4 or more SDRs. In the absence of affected FDRs and SDRs, there were significantly increased risks based on lung cancer–affected third-degree relatives (TDRs) ranging from 1.18 (CI 95%: 1.11, 1.24) for 1 or more affected TDRs to 1.55 (CI 95%: 1.03, 2.24) for 4 or more affected TDRs. RRs were significantly increased with earlier age at diagnosis of a FDR, and equivalent risks for maternal compared to paternal history were observed.ConclusionsThis study provides population-based estimates of lung cancer risk based on a proband’s complete family history (lung cancer constellation). Many individuals at two to five or more times increased risk for lung cancer are identified. Estimates of RR for lung cancer based on family history are arguably relevant clinically. The constellation RR estimates presented could serve in individual decision-making to direct resource use for lung cancer screening, and could be pivotal in decision-making for screening, treatment, and post-treatment surveillance.     

Cancer risk estimates for family members of a population-based family registry for breast and ovarian cancer.

Population-based breast and ovarian cancer family registries can facilitate studies to evaluate genetic and environmental factors in the etiology of these malignancies. The purpose of this study is to describe what is, as far as we know, the first population-based breast and ovarian cancer family registry and to estimate breast and ovarian cancer risk in relatives of breast and ovarian cancer probands. Population-based consecutive incident cases of breast and ovarian cancer were invited to participate in the University of California, Irvine breast and ovarian family registry. In this study, we report data on 1567 breast cancer and 328 ovarian cancer probands. The operational components of this family registry include enrollment of probands, family history interviewing, confidentiality, pathology, verification and review, biospecimen bank, statistical/genetic analysis, and special studies on positional cloning of known genes. All of the components are tracked through the University of California, Irvine Genetic Research Information System. In non-Hispanic-white breast cancer probands, relative risk (RR) of breast cancer in mothers and sisters is significantly elevated [RR = 1.7 and 95% confidence interval (CI) = 1.4-2.0 and RR = 2.8 and 95% CI = 2.3-3.3, respectively]. In families of ovarian cancer probands, mothers are at increased risk of ovarian cancer (RR = 4.6; 95% CI, 2.1-8.7). RR of breast cancer in mothers of Hispanic breast cancer probands is significantly elevated (RR = 4.9; 95% CI, 2.6-8.5). No elevation of breast or ovarian cancer risk was observed among relatives of Asian probands. In general, there is a decrease in RR among mothers and sisters with increase in age of onset of probands. In second-degree relatives and first cousins, the breast cancer hazards ratios increase with increase in the number of affected first-degree relatives and decrease with increase in age at onset of the proband.     

Risk for smoking-related cancer among relatives of lung cancer patients

Studies of familial aggregation of cancer provide indirect evidence for the role of genetic predisposition to cancer. In an ongoing case-control study, we evaluated whether first-degree relatives of lung cancer cases are at increased risk of lung and other cancers. Smoking-related cancers were defined as cancers of the lung, bladder, head and neck, kidney, and pancreas. The 806 probands included in this analysis were patients referred to The University of Texas M. D. Anderson Cancer Center (Houston, TX). We identified 663 controls, matched to the cases on age (+/-5 years), sex, ethnicity, and smoking history, who were recruited from a local multispecialty physician practice in the Houston metropolitan area. Self-reported cancer family history data were available for 6430 first-degree relatives of the cases and 4936 first-degree relatives of the controls. An excess of cancer in relatives was evaluated by comparing the observed cancer cases among relatives of the cases with relatives of the controls. We conducted further analysis after stratifying on age of lung cancer onset (age at study registration for controls) and smoking status (never, former, or current) of the probands. We also conducted Cox regression analysis and compared time to cancer diagnosis among the relatives of the cases and controls adjusted for age and smoking status of proband and family members. Siblings [relative risk (RR) = 1.85; P = 0.003] of cases had a significant excess of lung cancer and an excess of smoking-related cancers (RR = 1.29; P = 0.01). We observed evidence of familial aggregation (RR = 1.71; P < 0.001) of lung cancer among relatives of late-onset lung cancer cases. From the Cox regression, we observed a moderate risk for development of lung (RR = 1.25; P = 0.09) and other smoking-related cancers (RR = 1.23; P = 0.05). After adjustment for smoking behavior of probands and their relatives, the risks of lung cancer (RR = 1.33; P = 0.03) and smoking-related cancers (RR = 1.28; P = 0.02) were statistically significant. We further stratified on age at onset and observed no evidence (P = 0.81) of familial aggregation of lung cancer among young onset (相似文献   

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

Background

Inherited predisposition to pancreas cancer accounts for approximately 10% of cases. Familial aggregation may be influenced by shared environmental factors and shared genes. We evaluate whether a family history of pancreas cancer is a risk factor for ten specified cancers in first-degree relatives: bladder, breast, colon, head and neck, lung, lymphoma, melanoma, ovary, pancreas, and prostate.

Methods

Risk factor data and cancer family history were obtained for 1,816 first-degree relatives of pancreas cancer case probands (n?=?247) and 3,157 first-degree relatives of control probands (n?=?420). Unconditional logistic regression models using generalized estimating equations were used to estimate odds ratios (ORs), and 95% confidence intervals of having a first-degree relative a specified cancer.

Results

A family history of pancreas cancer was associated with a doubled risk of lymphoma (OR?=?2.83, 95% CI?=?1.02–7.86) and ovarian cancer (OR?=?2.25, 95% CI?=?0.77–6.60) among relatives after adjustment. Relatives with a family history of early-onset pancreas cancer in a proband had a sevenfold increased risk of lymphoma (OR?=?7.31, 95% CI?=?1.45 to 36.7). Relatives who ever smoked and had a family history of pancreas cancer had a fivefold increased risk of ovarian cancer (OR?=?4.89, 95% CI?=?1.16–20.6).

Conclusion

Family history assessment of cancer risk should include all cancers. Assessment of other known and suspected risk factors in relatives will improve risk evaluation. As screening and surveillance methods are developed, identifying those at highest risk is crucial for a successful screening program.     

Family history of breast cancer as a risk factor for ovarian cancer in a prospective study

BACKGROUND: A family history of breast cancer has been associated with increased ovarian cancer risk. However, few studies have assessed risk according to characteristics that suggest an inherited cancer susceptibility disorder, such as earlier-than-usual age at cancer diagnosis, family members with double primary cancers of different types, multiple relatives with cancer, and cancer in both members of paired organs. METHODS: Ovarian cancer risk was assessed according to a detailed breast cancer family history among 49,975 participants in the Breast Cancer Detection Demonstration Project Breast Cancer Defection Demenstration Project (BCDDP) Follow-up Study (1979-1998). In all, 362 incident ovarian cancers were identified during follow-up and rate ratios (RRs) were calculated by Poisson regression. RESULTS.: Breast cancer in a first- or second-degree relative was associated with increased risk of ovarian cancer (RR = 1.4; 95% confidence interval [CI] = 1.1-1.7). Having 2 or more affected first-degree relatives was associated with increased risk (RR = 1.8; 95% CI = 1.1-2.8), especially for women diagnosed with ovarian cancer before age 60 (RR = 4.2; 95% CI = 1.9-9.2) or with a personal history of breast cancer (RR = 3.7; 95% CI 1.8-7.7). Risk was also particularly high for women with 2 or more first-degree relatives with breast cancer and at least 1 affected relative diagnosed before age 50 (RR = 2.6; 95% CI = 1.4-4.8) or with bilateral breast cancer (RR = 4.2; 95% CI = 1.7-10). CONCLUSIONS: A detailed breast cancer family history as well as an individual's age and personal history of breast cancer are useful for identifying women at elevated genetic risk of ovarian cancer.     

Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers

The purpose of this study was to quantify the risk of cancers other than melanoma among family members of CDKN2A mutation carriers using data from the Genes, Environment and Melanoma study. Relative risks (RRs) of all non-melanoma cancers among first-degree relatives (FDRs) of melanoma patients with CDKN2A mutations (n = 65) and FDRs of melanoma patients without mutations (n = 3537) were calculated as the ratio of estimated event rates (number of cancers/total person-years) in FDRs of carriers vs noncarriers with exact Clopper-Pearson-type tests and 95% confidence intervals (CIs). All statistical tests were two-sided. There were 56 (13.1%) non-melanoma cancers reported among 429 FDRs of mutation carriers and 2199 (9.4%) non-melanoma cancers in 23?452 FDRs of noncarriers. The FDRs of carriers had an increased risk of any cancer other than melanoma (56 cancers among 429 FDRs of carrier probands vs 2199 cancers among 23?452 FDRs of noncarrier probands; RR = 1.5, 95% CI = 1.2 to 2.0, P = .005), gastrointestinal cancer (20 cancers among 429 FDRs of carrier probands vs 506 cancers among 23?452 FDRs of noncarrier probands; RR = 2.4, 95% CI = 1.4 to 3.7, P = .001), and pancreatic cancer (five cancers among 429 FDRs of carrier probands vs 41 cancers among 23?452 FDRs of noncarrier probands; RR = 7.4, 95% CI = 2.3 to 18.7, P = .002). Wilms tumor was reported in two FDRs of carrier probands and three FDRs of noncarrier probands (RR = 40.4, 95% CI = 3.4 to 352.7, P = .005). The lifetime risk of any cancer other than melanoma among CDKN2A mutation carriers was estimated as 59.0% by age 85 years (95% CI = 39.0% to 75.4%) by the kin-cohort method, under the standard assumptions of Mendelian genetics on the genotype distribution of FDRs conditional on proband genotype.     

Family history of cancer and stomach cancer risk

A family history of stomach cancer in first-degree relatives increases the risk of stomach cancer, but uncertainties remain as concerns the variation of the risk according to age, sex and type of relative, as well as on the role of family history of other cancers. We investigated the issue using data from a multicentric case-control study conducted in Italy between 1997 and 2007 on 230 cases aged not more than 80 years, with histologically confirmed incident gastric cancer and 547 controls admitted to hospital for acute, non neoplastic conditions. Logistic regression models adjusted for the effect of sex, age, year of interview, education, body mass index (BMI), tobacco smoking and number of brothers and sisters were used to estimate the odds ratios (OR) of stomach cancer. Relative to subjects with no history, those with a family history of gastric cancer had an OR of 2.5 (95% confidence interval (CI) 1.5-4.2). No significant heterogeneity emerged according to sex or age of the proband or of the affected relative, or smoking habits, BMI and education of the proband. As suggested from previous studies the OR was higher when the affected relative was a sibling (OR=5.1, 95% CI: 1.3-20.6) rather than a parent (OR=2.2, 95% CI: 1.2-3.9), although the heterogeneity test was not significant. The risk of stomach cancer was not increased in subjects with a family history of cancer at any other site. The OR for all sites excluding stomach was 1.0 (95% CI: 0.7-1.4).     

Family history of cancer and risk of lung cancer among nonsmoking Chinese women.

The relationship between family cancer history in first-degree relatives and risk of lung cancer was evaluated among a population-based cohort of 71,392 female nonsmokers in Shanghai, China. A total of 179 newly diagnosed lung cancer patients were identified during 441,410 person-years of follow-up. Lung cancer risk was not elevated among those with a family history of lung cancer. However, risk of lung cancer was increased among subjects who had two or more first-degree relatives with any type of cancers {rate ratio [RR], 1.95 [95% confidence intervals (95% CI), 1.08-3.54] for two relatives with any cancers and RR, 3.17 [95% CI, 1.00-10.03] for three or more relatives with any cancer}. Having a family history of colorectal cancer (RR, 2.38; 95% CI, 1.21-4.70) and having siblings with stomach cancer (RR, 2.16; 95% CI, 1.01-4.65) and pancreatic cancer (RR, 4.19; 95% CI, 1.04-16.95) were also found to be associated with lung cancer risk. This cohort study indicated a moderate association of lung cancer risk with a family cancer history in general, but not with a family history of lung cancer specifically. The associations were stronger when a sibling, rather than a parent, was affected. The apparent link between lung cancer risk and a family history of colorectal, stomach, and pancreas cancers may be worth further investigation.     

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Bladder cancer risk as modified by family history and smoking

BACKGROUND: The familial risk of bladder cancer (BC) is not well understood and, to date, little attention has been paid to the joint effect of smoking and family history in modifying the risk of BC. The authors investigated the role of family history in association with the risk of BC. METHODS: Case and control probands were identified as part of an on-going BC case-control study. The relative risk associated with a family history of BC was estimated. RESULTS: In total, 713 cases and 658 controls were included. In a case-control analysis, compared with individuals who never smoked and who had no family history of BC, probands who had smoked and who also had a positive family history were at 5.31-fold increased risk of BC (P for interaction = .04). The 713 case probands and the 658 controls reported 5160 and 4816 first-degree relatives, respectively. Compared with never-smoking relatives who had probands diagnosed with BC at an older age (age >65 years), ever-smoking relatives who had probands diagnosed at a younger age (ages 40-65 years) showed a 6.89-fold (95% confidence interval, from 2.25-fold to 21.12-fold) increased risk. Similar results were obtained for the joint effects of family history of BC and smoking. CONCLUSIONS. The current results indicated that a positive family history of BC may have interacted with smoking habits to increase the risk of BC in the study population.     

Cancer risk in the relatives of patients with nasopharyngeal carcinoma—a register-based cohort study in Sweden

Background:

Little is known about cancer susceptibility among relatives of nasopharyngeal carcinoma (NPC) patients in non-endemic areas. We conducted a register-based cohort study to assess the relative risks (RRs) of cancer in families of NPC probands in Sweden.

Methods:

By linking 11 602 616 Swedish-born individuals (defined as ‘general population'') identified from national censuses to the Swedish Cancer Register and Multi-Generation Register, we identified 9157 relatives (3645 first-degree and 5512 second-degree) of 1211 NPC probands. Cancer incidence during 1961–2009 was ascertained through the Cancer Register. Relative risks of cancer in the relatives of NPC probands, compared with the rest of the general population, were calculated from Poisson regression models.

Results:

First-degree relatives had higher risks of NPC (N=2, RR=4.29, 95% confidence interval (CI)=1.07 to 17.17) and cancers of the larynx (N=5, RR=2.53, 95% CI=1.05 to 6.09), prostate (N=76, RR=1.35, 95% CI=1.07 to 1.68), and thyroid (N=10, RR=2.44, 95% CI=1.31 to 4.53) than the rest of the general population. In addition, a raised risk of cancer of the salivary glands was observed among first-degree relatives of probands with undifferentiated NPC (N=2, RR=6.64, 95% CI=1.66 to 26.57). In contrast, a decreased risk of colorectal cancer was observed in first- and second-degree relatives (N=43, RR=0.71, 95% CI=0.53 to 0.96).

Conclusion:

The increased risk of NPC and certain other cancers among first-degree relatives may be explained by shared genetic and environmental risk factors, the latter including Epstein–Barr virus infection and smoking or by increased diagnostic intensity.     

Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer.

BACKGROUND: Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population. METHODS: We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects). RESULTS: Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (<50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8. 48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1. 49-7.56). CONCLUSIONS: Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population.     

Cancer risks in first-degree relatives of CHEK2 mutation carriers: effects of mutation type and cancer site in proband

It is important to have accurate knowledge of the range of cancers associated with various CHEK2 mutations, and of the lifetime risks of cancer associated with each. We wished to establish the relationship between family history, mutation type and cancer risk in families with a CHEK2 mutation. We obtained a blood sample and pedigree information from 2012 unselected women with breast cancer, from 2007 men with prostate cancer and from 1934 patients with colon cancer, from hospitals throughout Poland. Genetic testing was carried out for four founder CHEK2 mutations on all 5953 specimens and 533 carriers were identified. We estimated the risk to age 75 for any cancer in the 2544 first-degree relatives to be 22.3%. After adjusting for mutation type, the risk of breast cancer was much higher among relatives of probands with breast cancer than among relatives of patients with prostate or colon cancer (HR=3.6; 95% CI=2.1–6.2; P=0.0001). Similarly, the risk of prostate cancer was higher among relatives of probands with prostate cancer than among relatives of patients with breast or colon cancer (HR=4.4; 95% CI=2.2–8.7; P=0.0001) and the risk of colon cancer was higher among relatives of probands with colon cancer than among relatives of patients with prostate or breast cancer (HR=4.2; 95% CI=2.4–7.8; P=0.0001). These analyses suggest that the risk of cancer in a carrier of a CHEK2 mutation is dependent on the family history of cancer.     

Family history and the risk of stomach cancer death in Japan: differences by age and gender.

Familial aggregation of stomach cancer has long been observed. The effect on disease risk of family history and its magnitude according to the type of affected relatives, however, is not well known. We conducted a prospective analysis using the JACC study (Japan Collaborative Cohort Study For Evaluation of Cancer Risk, sponsored by Monbusho) data. During the follow-up period, 662 stomach cancer deaths were documented. A positive history of stomach cancer in one or more first-degree relatives was associated with a significantly increased risk of death from the disease in both men (RR 1.60; 95% CI 1.11-2.31) and women (RR 2.47; 95% CI 1.50-4.06). In the subanalysis stratified by age, the association between positive family history and stomach cancer was stronger in the age group from 40-59 (RR 2.62; 95% CI 1.34-5.11 for men and RR 5.88; 95% CI 2.70-12.82 for women) than in the age group from 60-79 (RR 1.31; 95% CI 0.84-2.05 for men and RR 1.44; 95% CI 0.72-2.88 for women). In the age group from 40-59, men with father's history and women with mother's and sister's history of the disease had a significantly increased risk (RR 3.14; 95% CI 1.51-6.55, RR 10.46; 95% CI 4.54-24.12, RR 13.39; 95% CI 3.89-46.12, respectively). When 2 or more family members were affected, the increment in the risk was prominent especially in women (RR 9.45; 95% CI 4.46-20.05). These results suggest the existence of a certain subtype of stomach cancer that is inherited more often by women from one generation to the next in gender-influenced fashion. Any preventive strategy should take into account the degree of individual susceptibility.     

Familial aggregation of early-onset cancers in early-onset breast cancer families

The risk of early-onset (EO) breast cancer is known to be increased in relatives of EO breast cancer patients, but less is known about the familial risk of other EO cancers. We assessed familial risks of EO cancers (aged ≤40 years) other than breast cancer in 54 753 relatives of 5562 women with EO breast cancer (probands) by using a population-based cohort from Finland. Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) were estimated by using gender-, age- and period-specific cancer incidences of the general population as reference. The risk of any cancer excluding breast cancer in first-degree relatives was comparable to population cancer risk (SIR 0.99, 95% CI: 0.84-1.16). Siblings' children of women with EO breast cancer were at an elevated risk of EO testicular and ovarian cancer (SIR = 1.74, 95% CI: 1.07-2.69 and 2.69, 95% CI: 1.08-5.53, respectively). The risk of EO pancreatic cancer was elevated in siblings of the probands (7.61, 95% CI: 1.57-22.23) and an increased risk of any other cancer than breast cancer was observed in children of the probands (1.27, 95% CI: 1.03-1.55). In conclusion, relatives of women with EO breast cancer are at higher familial risk of certain discordant EO cancers, with the risk extending beyond first-degree relatives.     

Racial differences in the familial aggregation of breast cancer and other female cancers

Summary Although breast cancer familial aggregation has been studied in Caucasians, information for African–Americans is scant. We used family cancer history from the Womens Contraceptive and Reproductive Experiences study to assess the aggregation of breast and gynecological cancers in African–American and Caucasian families. Information was available on 41,825 first and second-degree relatives of Caucasian and 28,956 relatives of African–American participants. We used a cohort approach in which the relatives cancer status was the outcome in unconditional logistic regression and adjusted for correlated data using generalized estimating equations. Race-specific models included a family history indicator, the relatives age, and type. Relative risk (RR) estimates for breast cancer were highest for first-degree relatives, and the overall RR for breast cancer among case relatives was 1.96 (95% CI = 1.68–2.30) for Caucasian and 1.78 (95% CI = 1.41–2.25) for African–Americans. The effect of CARE participants reference age on their relatives breast cancer risk was greatest among first-degree relatives of African–American patients with RRs (95% CI) for ages <45 and 45 of 2.97 (1.86–4.74) and 1.48 (1.14–1.92), respectively. Among Caucasians, first-degree relatives of case subjects were at greater risk for ovarian cancer, particularly relatives younger than 45 years (RR (95% CI) = 2.06 (1.02–4.12)), whereas African–American first-degree relatives of case subjects were at increased cervical cancer risk (RR (95% CI) = 2.17 (1.22–3.85). In conclusion, these racially distinct aggregation patterns may reflect different modes of inheritance and/or environmental factors that impact cancer risk.*The first two authors contributed equally to this work.     

Mammographic densities and risk of breast cancer among subjects with a family history of this disease.

BACKGROUND: A family history of breast cancer is known to increase risk of the disease, but other genetic and environmental factors that modify this risk are likely to exist. One of these factors is mammographic density, and we have sought evidence that it is associated with increased risk of breast cancer among women with a family history of breast cancer. METHODS: We used data from a nested case-control study based on the Canadian National Breast Screening Study (NBSS). From 354 case patients with incident breast cancer detected at least 12 months after entry into the NBSS and 354 matched control subjects, we analyzed subjects who were identified as having a family history of breast cancer according to one of three, nonmutually exclusive, criteria. We compared the mammographic densities of case patients and control subjects by radiologic and computer-assisted methods of measurement. RESULTS: After adjustment for other risk factors for breast cancer, the relative risks (RRs) between the most and least extensive categories of breast density were as follows: For at least one first-degree relative with breast cancer, RR = 11.14 (95% confidence interval [CI] = 1.54-80.39); for at least two affected first- or second-degree relatives, RR = 2.57 (95% CI = 0.23-28.22); for at least one first- or second-degree relative with breast cancer, RR = 5.43 (95% CI = 1.85-15.88). CONCLUSIONS: These results suggest that mammographic density may be strongly associated with risk of breast cancer among women with a family history of the disease. Because mammographic densities can be modified by dietary and hormonal interventions, the results suggest potential approaches to the prevention of breast cancer in women with a family history of breast cancer.     

Family history of breast cancer and breast cancer risk in Japan

We studied 132 families with a family history of breast cancer (familial aggregation cases, FA cases) to assess the breast cancer risk presented by such a family history. For comparison with these FA cases, we randomly selected 132 control families of sporadic cases (SP controls) by adjusting for the age of the proband at surgery. Information on family history was collected for all first-degree female relatives and maternal and paternal grandmothers. Japanese women with a first-degree relative affected by breast cancer were found to have an increased risk of the disease. The odds ratio (OR) for women with a family history of breast cancer was 1.99 (95% confidence interval [ CI ], 1.48-2.66). The OR for FA-case doughters of women with breast cancer was 1.54 (95% CI, 0.91-2.63). A higher risk was not observed if a woman's mother had breast cancer. If the proband had a sister with breast cancer, a slightly increased risk of other cancers of the proband was observed (OR, 1.85 [ 0.87-3.92]). These results suggest that a family history of breast cancer in Japanese women may affect their risk of developing cancer of the breast and other organs.     

Family history and colorectal cancer: predictors of risk

INTRODUCTION: While the association between family history of colorectal cancer in first-degree relatives and risk of developing colon cancer has been well defined, the association with rectal cancer is much less clear. The purpose of this study is to define rectal cancer risk associated with family history of colorectal cancer in first-degree relatives. We also evaluate diet and lifestyle factors associated with developing colorectal cancer among participants with a positive family history. METHODS: Data were available from two population-based case--control studies of colon and rectal cancer. Participants were members of the Kaiser Permanente Medical Care Program (KPMCP) or residents of the state of Utah. Cases were first primary colon cancer diagnosed between 1991 and 1994 (n = 1308 cases and 1544 controls) or rectal cancer diagnosed between 1997 and 2001 (n = 952 cases and 1205 controls). RESULTS: A family history of colorectal cancer in any first-degree relatives slightly increased risk of rectal cancer (OR: 1.37 95% CI: 1.02-1.85). Family history of colorectal cancer was associated with the greatest risk among those diagnosed at age 50 or younger (OR: 2.09 95% CI: 0.94-4.65 for rectal tumors; OR: 3.00 95% CI: 0.98-9.20 for distal colon tumors; and OR: 7.88 95% CI: 2.62-23.7 for proximal colon tumors). Factors significantly associated with cancer risk among those with a family history of colorectal cancer, included not having a sigmoidoscopy (OR: 2.81 95% CI: 1.86-4.24): a diet not Prudent, i.e. high in fruits, vegetables, whole grains, fish and poultry, (OR: 2.79 95% CI: 1.40-5.56); smoking cigarettes (OR: 1.68 95% CI: 1.12-2.53), and eating a Western diet, i.e. a diet high in meat, refined grains, high-fat foods, and fast foods, (OR: 2.15 95% CI: 1.06-4.35). Physical inactivity was not associated with increased cancer risk among those with a positive family history of colorectal cancer. SUMMARY: These results confirm observations reported by others that a family history of colorectal cancer increases risk of cancer among those diagnosed at a younger age. Associations with family history are weakest for rectal cancer and strongest for proximal colonic tumors. Since several diet and lifestyle factors influence development of cancer among those with a family history of the disease, there appears to be practical approaches for individuals with a family history of colorectal cancer to reduce their cancer risk.     

Family history of cancer and the risk of prostate cancer and benign prostatic hyperplasia

We analysed the relation between family history of cancer in first-degree relatives and risk of prostate cancer (PC) and benign prostatic hyperplasia (BPH) using data from a multicentric case-control study conducted in Italy from 1991 to 2002 on 1,294 cases of incident, histologically confirmed PC, 1,369 cases of BPH and 1,451 men admitted to the same network of hospitals for acute, nonneoplastic conditions. Unconditional logistic regression was used to estimate odds ratios (OR) of PC and BPH, adjusted for age and other confounders. Men with a family history of PC had an OR of PC of 4.0 (95% confidence interval [CI] 2.5-6.5), and the risk was higher when the proband was younger, when 2 or more relatives were affected or when the affected relative was a brother. The risk of PC was also increased in men with a family history of cancer of the ovary (OR = 6.2, 95% CI 1.2-32), bladder (OR = 3.5, 95% CI 1.6-7.4) and kidney (OR = 3.1, 95% CI 1.1-8.5). An involvement of breast/ovarian cancer predisposition genes in a small proportion of PCs was suggested by the cluster of these cancers in female relatives of a few PC cases. The risk of BPH was increased in men with a family history of bladder cancer (OR = 2.2, 95% CI 1.0-5.0) but not PC (OR = 1.2, 95% CI 0.7-2.2). Our study adds further information on the association of family history of cancer and risk of PC and is, to our knowledge, the first comprehensive epidemiologic information on family history of cancer and risk of BPH.