Evaluation of familial clustering of breast and prostate cancer in the Minnesota Breast Cancer Family Study

Few studies examining familial clustering of breast and prostate cancer (PC) have focused on a clearly defined high-risk population with epidemiologic risk factors. We conducted a cohort study of prostate cancer among a subset of 426 families ascertained through female breast cancer probands. Three groups of males were included: 804 relatives in 60 families with four or more breast or ovarian cancers, 536 marry-ins in these high-risk families, and 484 relatives in 81 families where only the proband had breast cancer. A total of 118 prostate cancers were reported. The rate of prostate cancer among blood relatives in high-risk families was significantly lower than among marry-ins (RR = 0.6, 95% C.I.: 0.4-0.9). The rate of prostate cancer among blood relatives in low-risk families was not significantly different from the rate among marry-ins (RR = 0.8, 95% C.I.: 0.5-1.2). These results provide little evidence that male relatives in high-risk breast cancer families are at increased risk of prostate cancer.     

Cancer experience in the relatives of an unselected series of breast cancer patients.

First- and second-degree relatives of an unselected series of 402 breast cancer patients have been studied for their cancer experience. In the first-degree relatives an excess of all cancers is seen [overall relative risk (RR) = 1.28, P = 0.002; males RR = 1.26, P = 0.047; females RR = 1.30, P = 0.022). There is a marked excess of sarcoma (RR = 4.26, P = 0.0064); females are at high risk of breast cancer (RR = 2.68, P < 0.0001) and males have an excess of carcinoma of the lip, oral cavity and pharynx (RR = 4.22, P = 0.0032). Second-degree relatives have a non-significant excess of all cancers (RR = 1.14, P = 0.14); females have a borderline excess of breast cancer (RR = 1.53, P = 0.08) and an excess of carcinoma of the kidney (RR = 7.46, P = 0.0012) and males have an excess of carcinoma of the trachea and lung (RR = 1.50, P = 0.032). No excess of prostate or ovarian carcinoma was seen. Relatives are at slightly higher risk if the index patient is diagnosed between the ages of 40 and 49 (first-degree RR = 1.64, P = 0.007; second-degree RR = 1.43, P = 0.02). The excess of cancers, including breast cancers, is not limited to a few high-risk families, but appears to be spread across many. These observations may be accounted for by shared environmental factors within families or a common predisposing gene with low penetrance.     

Risk of cancer at sites other than the breast in Swedish families eligible for BRCA1 or BRCA2 mutation testing.

BACKGROUND: Population-based data on the risk of cancer in families eligible for BRCA1/2 mutation testing may help to reach a consensus about the association of BRCA1/2 mutations with cancer at sites other than the breast and may reveal new, non-BRCA1/2 related components of the familial clustering of cancer in those families. PATIENTS AND METHODS: The families of the Swedish Family-Cancer Database with at least three generations (n = 944,723) were classified according to the criteria proposed by the German Consortium for Hereditary Breast and Ovarian Cancer. The cancer incidences in the classified families were compared with the incidences in the general population. The percentages of individuals with cancer in families eligible for BRCA1/2 mutation testing were compared with data in the literature to estimate the proportion of malignancies related to BRCA1/2 mutations. RESULTS: Families with two breast cancers before the age of 50 years showed increased risk of early onset pancreatic, prostate and ovarian cancers; families with ovarian and breast cancers presented increased incidences for ovarian and ocular cancers; families with two breast cancers, at least one of them under the age of 50 years, showed increased risks of prostate and primary liver cancers. Stomach cancer before age 70 years was twice as frequent in families with breast and ovarian cancers as in the general population. BRCA1/2 mutations probably explain most of the aggregation of ovarian cancer in families with male breast cancer, and in families with at least two breast cancers diagnosed before age 50 years. CONCLUSIONS: The association of BRCA1/2 mutations with ovarian, pancreatic, prostate and stomach cancers was confirmed at a population level. However, the clustering of early pancreatic cancer in families with two breast cancers under age 50 years, the aggregation of ovarian cancer in families with breast and ovarian cancers, and the increased incidence of early onset prostate cancer in families with male breast cancer seem to be due to other effects unrelated to BRCA1/2 mutations.     

A multicenter study of cancer incidence in CHEK2 1100delC mutation carriers.

The CHEK2 1100delC protein-truncating mutation has a carrier frequency of approximately 0.7% in Northern and Western European populations and confers an approximately 2-fold increased risk of breast cancer. It has also been suggested to increase risks of colorectal and prostate cancer, but its involvement with these or other types of cancer has not been confirmed. The incidence of cancer other than breast cancer in 11,116 individuals from 734 non-BRCA1/2 breast cancer families from the United Kingdom, Germany, Netherlands, and the United States was compared with that predicted by population rates. Relative risks (RR) to carriers and noncarriers were estimated by maximum likelihood, via the expectation-maximization algorithm to allow for unknown genotypes. Sixty-seven families contained at least one tested CHEK2 1100delC mutation carrier. There was evidence of underreporting of cancers in male relatives (422 cancers observed, 860 expected) but not in females (322 observed, 335 expected); hence, we focused on cancer risks in female carriers. The risk of cancers other than breast cancer in female carriers was not significantly elevated, although a modest increase in risk could not be excluded (RR, 1.18; 95% confidence interval, 0.64-2.17). The carrier risk was not significantly raised for any individual cancer site, including colorectal cancer (RR, 1.60; 95% confidence interval, 0.54-4.71). However, between ages 20 to 50 years, the risks of colorectal and lung cancer were both higher in female carriers than noncarriers (P = 0.041 and 0.0001, respectively). There was no evidence of a higher prostate cancer risk in carriers than noncarriers (P = 0.26), although underreporting of male cancers limited our power to detect such a difference. Our results suggest that the risk of cancer associated with CHEK2 1100delC mutations is restricted to breast cancer, although we cannot rule out a small increase in overall cancer risk.     

Cancer in the families of children with soft tissue sarcoma

The cancer experience among 754 first-degree relatives (mothers, fathers, and siblings) of a population-based series of 177 children with soft tissue sarcoma is reported. The current study represents an extension of our earlier work in which the authors found an excess of breast cancer in the mothers of 143 of these children. There were 40 cancers among all first-degree relatives, compared with 24.82 expected (relative risk [RR] 1.61, P = 0.006). There was no excess in fathers, but an excess of borderline significance was seen in mothers (RR 1.67, P = 0.0545), and a significant excess in siblings (RR 4.55, P = 0.0002), mainly due to carcinoma of the breast and pediatric tumors. Results of a step forward Cox multivariate analysis identified three variables in the index child which were independently associated with high cancer risk in relatives, as follows: age younger than 24 months at diagnosis; histologic type, embryonal rhabdomyosarcoma or other and unspecified soft tissue sarcoma; and male sex. It was possible, therefore, to identify a subgroup of children whose relatives are at high risk of early onset cancer (RR in this group 10.14). The pattern of cancers is consistent with the Li-Fraumeni syndrome. The authors conclude that a marked proportion of childhood soft tissue sarcoma has a genetic basis.     

A follow-up study of breast and other cancers in families of an unselected series of breast cancer patients

The cancer experience among relatives of an unselected cohort of 402 breast cancer patients was previously reported. Cases and their first degree relatives were flagged at the National Health Service Central Register for continuous notification of cancer registrations and deaths. More than 10 years of follow-up data have been analysed to update cancer risks overall and to estimate breast cancer risk in relatives prospectively according to family history at the time of breast cancer diagnosis in the index case. Significant excesses of breast cancer (RR 2.24, P<0.0001), prostate cancer (RR 1.71, P=0.039) and bone sarcoma (RR 6.564, P=0.042) overall and soft tissue sarcoma in mothers only (RR 15.44, P=0.001) were found. There was no excess of any other cancer, including ovarian. High breast cancer risk in relatives was associated with young age at diagnosis in the index (index <40 years at diagnosis, RR in relatives 3.76, P=0.004). Prospective risk of breast cancer was higher in relatives of index patients who had an affected first degree relative at the time of their diagnosis (no family history, RR 1.87, P=0.012; with a family history, RR 3.72, P=0.015). These prospective risk estimates are valuable in advising relatives of newly diagnosed breast cancer patients.     

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   

Investigation of an interaction of alcohol intake and family history on breast cancer risk in the Minnesota Breast Cancer Family Study

BACKGROUND: One explanation for the variability in results in studies of alcohol consumption and breast cancer could be the presence of effect modifiers, such as genetic susceptibility. The authors examined the interaction of alcohol and family history of breast cancer on breast cancer risk in a population-based family study of 426 multigenerational breast cancer families. The authors evaluated whether alcohol use was a stronger risk factor for breast cancer among sisters, daughters, nieces, and granddaughters of breast cancer probands than among women who married into these families. METHODS: Analyses were performed on surrogate and self-reported data combined and on self-reported data alone. To evaluate the interaction of alcohol and breast cancer risk among women with a family history of breast cancer, the authors performed analyses on all 426 families and on a subset of 132 families that had 3 or more breast and/or ovarian cancers in their family. RESULTS: A total of 9032 blood relatives and marry-ins and 558 breast cancer cases were available for analysis. In the entire 426 families, there was a suggestion of an interaction of relationship to the proband and frequency of alcohol consumption on breast cancer risk (P(interaction) = 0.14) for surrogate and self-reported information combined. Among first-degree relatives of the proband, daily drinkers had a significantly increased risk of breast cancer compared with never drinkers (RR = 2.45 [1.20, 5.02]), but this increase was less evident among second-degree relatives who reported daily alcohol intake (RR = 1.27 [0.73, 2.22]) and was not evident in marry-ins who reported daily use of alcohol (RR = 0.90 [0.42, 1.90]). The findings based on the subset of 132 high-risk families with 3 or more breast and/or ovarian cancers were similar to findings based on all 426 families (P(interaction) = 0.07). An interaction of family history with alcohol use was also suggested when the analyses were restricted to self-respondents, although the interaction test P-value was no longer of borderline significance. CONCLUSION: An increased risk of breast cancer due to an increased frequency of alcohol consumption may be limited to women with a family history of breast cancer.     

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 variation associated with the position of the mutation in the BRCA2 gene

Inherited mutations of the BRCA2 gene give rise to a multi-site cancer phenotype which includes breast cancer (in female and males), ovarian, pancreatic and prostate cancer, ocular and other melanomas, laryngeal, colon and stomach cancers. Interpretation of test results and risk assessment is therefore complex. It has been proposed that families with mutations in the ovarian cancer cluster region (OCCR) of exon 11 (nucleotides 3035-6629) express a higher ratio of ovarian to breast cancer, than families with mutations elsewhere in the BRCA2 gene. In this study we have investigated the presence of 7 types of cancer (ovary, male breast, pancreas, prostate, colon, stomach and melanoma) in first- and second-degree relatives of mutation-positive individuals in 440 families with a BRCA2 mutation. We reviewed histories of cancer in relatives among families with mutations distributed throughout the gene. Families with ovarian cancer were more likely to harbour mutations in the OCCR (nucleotides 3035-6629) than elsewhere in the gene (OR = 2.21; P = 0.0002). We also compared cancer risks according to ethnic group. Ashkenazi Jewish families with the 6174delT founder mutation were more likely to have a family member with ovarian cancer (OR = 1.58; P = 0.002) and less likely to have a family member with prostate cancer (OR = 0.62; P = 0.04) than were non-Jewish families. In contrast, a reduced presence of ovarian cancer was found in families of French-Canadian ancestry, compared to other ancestries (OR = 0.37; P = 0.0026). A high risk of male breast cancer was observed with the 6503delTT mutation (OR = 15.7; P = 0.023). Families of Polish ancestry had a reduced frequency of pancreatic cancer (OR = 0.0; P = 0.03) compared to families of other ethnic origins. In conclusion, both the position of mutation and the ethnic background of the family appear to contribute to the phenotypic variation observed in families with BRCA2 mutations.     

Familial effects of prostate and other cancers on lifetime breast cancer risk

Summary Lifetime probabilities of developing breast cancer were calculated for first-degree female relatives of three groups of breast cancer patients: 114 with bilateral cancer, 186 unselected, and 88 males. The patients were classified according to whether they had a family history of prostate, endometrial, or ovarian cancer, or no family history of these cancers. In families of unselected female and male patients with no family history of prostate, endometrial, or ovarian cancer, the lifetime probability of developing breast cancer was 11.4%. The risk increased slightly to 13.5% when these other cancers may or may not have present (i.e., they were ignored, which is the usual method in computing risks) and increased further to 25.5% when prostate, endometrial, or ovarian cancer was present in the family. In families of patients with bilateral cancer the respective risks were 10.9%, 17.3%, and 34.4%. A family history of prostate cancer increased lifetime risk consistently in each of the groups, to 29.0% in the unselected and male groups and to 38.2% in the bilateral group. Endometrial cancer increased risk only in the bilateral group (to 41.8%) as did ovarian cancer (to 54.6%). Increased risk of breast cancer with a family history of endometrial or ovarian cancer appeared to be influenced by families with hereditary breast-ovarian cancer or the cancer family syndrome. The results indicate that prostate cancer, and endometrial and ovarian cancers in some families, can significantly increase breast cancer risk and should be taken into account when counseling women about their breast cancer risk.     

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.     

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.     

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.     

Breast cancer risks in relatives of male breast cancer patients.

BACKGROUND: Previous studies have provided conflicting results concerning the familial effect of male breast cancer on breast cancer risks in female relatives. PURPOSE: We studied breast cancer risks in first-degree relatives of male patients and compared them with relatives of female patients. METHODS: Our study included 88 consecutively ascertained male patients and 320 of their first-degree relatives as well as 186 consecutively ascertained female patients and 633 of their first-degree relatives. Observed numbers of breast cancers in relatives were compared with the expected number derived from the Connecticut Tumor Registry. Multiple logistic regression analysis was also performed. RESULTS: Relatives of male patients exhibited a significant twofold increased risk when compared with expected rates and no difference in risk when compared with that of relatives of female patients. Prostate cancer in the family of a male patient resulted in a significant fourfold increased breast cancer risk compared with a risk of 1.4 in families with no history of prostate cancer. A family history of lung cancer, colon cancer, or melanoma had no effect on increasing risks of breast cancer. CONCLUSION: The familial effect of male breast cancer is the same as that of female breast cancer. IMPLICATIONS: Any estimates of breast cancer risk provided to individuals should also consider the occurrence of prostate cancer in the family, since prostate cancer appears capable of at least doubling the underlying twofold risk.     

The clinical utility of genetic testing in breast cancer kindreds: a prospective study in families without a demonstrable BRCA mutation

We report prospectively observed risk for breast cancer in breast cancer kindreds without a demonstrable BRCA1/2 mutation. According to family history, the optimal available member(s) of each breast cancer kindred attending our clinic was tested for BRCA mutations. Women in families without a demonstrable BRCA mutation were subjected to annual mammography. BRCA mutations were demonstrated in 496/2,118 (23 %) breast cancer kindreds. In families without a demonstrable BRCA mutation, a total of 3,161 healthy women aged 25–59 years were prospectively followed for 24,808 observation years. Sixty-four cancers were observed, compared to 34.0 expected (p < 0.01), arriving at a 7.9 % cumulative risk at age 60 compared to 4.0 % in the population [relative risk (RR) = 2.0]. Women with one mother or sister affected ≤50 years and with no other close relatives with breast cancer did not have increased risk (0 cancers observed and 0.6 expected at age 40, 11 cancers observed and 7.9 expected at age 60, p > 0.05). Excluding these, cumulative risk at 60 years was 8.8 % (RR = 2.2). The highest cumulative risk at 60 years was 11.4 %, found in families with two cases ≤55 years (RR = 2.8). In breast cancer kindreds without a demonstrable BRCA mutation, the risk for breast cancer in female first degree relatives was about twice the risk in the general population. Women with one early affected relative only did not have increased risk for early onset breast cancer, while those with more than one young affected relative had close to three times population risk.     

Aggregation of cancer among relatives of never-smoking lung cancer patients

The authors evaluated the familial aggregation of lung and other cancers in first-degree relatives of lung cancer patients self-reported to be lifetime never smokers. The data, derived from a large lung cancer case-control study, included 2,465 first-degree relatives of 316 never smoker lung cancer cases and 2,441 first-degree relatives of 318 never smoker controls, frequency matched to the cases on age, gender and ethnicity. The median age of the cases and the controls was 61 years, about 2/3 were women, and about 80% were Caucasian. Overall, there was a 25% excess risk [95% CI (1.05-1.50)] of any type of cancer among the first-degree relatives of cases, and case offspring exhibited a 2-fold excess cancer risk (1.03-4.10) compared with control offspring. There was also a 44% excess risk (1.05-1.97) of young onset cancers (before age 50) among relatives of cases. Smoking case relatives had an increased risk of any cancer [odds ratio (OR) = 1.36 (1.03-1.81)] and a 5.52-fold risk (1.19-25.51) of young onset lung cancer compared with smoking control relatives. Female case relatives had a 58% excess breast cancer risk (1.04-2.43), and case mothers a 2.57-fold breast cancer risk (1.16-4.24). A significant excess of testicular cancer was observed among case male relatives [OR = 12.32 (1.71-88.90)], although based on only 9 cases. The age at lung cancer diagnosis tended to be earlier in case relatives (61.4, SD = 12.9) compared with control relatives (66.2, SD = 11.4; p = 0.07). Our analysis provides further evidence for the importance of genetic factors for lung cancer in never smokers.     

Breast cancer family history as a risk factor for early onset breast cancer

Summary Since full breast cancer screening is not generally recommended for young women, it is important to identify individuals who are at higher risk for early onset breast cancer. We investigated the relationship between age of onset of breast cancer in 328 probands (consecutively ascertained patients from our oncology clinic) and breast cancer incidence and age of onset in their female relatives. We found that a family history of early onset breast cancer was associated with higher risk of early onset breast cancer. A family history of early onset breast cancer occurred more frequently among young (<40) breast cancer probands than among older (40) breast cancer probands (p<0.001; OR = 23). This relationship was particularly evident when the analysis was restricted to thehereditary breast cancer probands (p<0.001; OR = 44). We also observed a positive family history of breast cancer (any age) more frequently in young breast cancer probands than in older breast cancer probands (p<0.001; OR = 2.8). These observations have important pragmatic implications for surveillance. We recommend intense surveillance for breast cancer, initiated earlier, for women with close relatives diagnosed with early onset breast cancer.     

Risk of cancer in relatives of testicular cancer patients.

The incidence of cancer at sites other than the testis has been investigated in the families of 797 Norwegian and 178 Swedish patients diagnosed with testicular cancer during 1981-91. In the families of the Norwegian patients, the total number of cancers in the relatives was significantly lower than the expected number derived from national incidence rates [observed number of cancers 250, expected number of cancers 281.92, standardised incidence ratio (SIR) 0.89, 95% confidence interval (CI) 0.78-1.00]. This finding can be accounted for almost entirely by the finding of fewer than expected prostate and gastrointestinal cancers in the parents of cases. The other common cancers were found at slightly lower than or near the expected levels in the relatives. In the Swedish cohort, which accounts for less than 20% of cases, the observed number of cancers was very close to the expected number. Fourteen fathers of cases had prostate cancer compared with 27.57 prostate cancers expected, giving a SIR of 0.51 (P=0.006). Mothers had more lung cancers (ten cases observed, SIR=2.11, P=0.04) and cancers of the endometrium than expected (13 cases observed, SIR=1.73, P=0.09). These findings may be interpreted as support for theories proposing hormonal dysfunction as causing testicular cancer. Fifty-four gastrointestinal cancers were observed in the parents compared with 68.48 expected (SIR=0.78, P=0.082). Furthermore, testicular cancer was not found to be associated with the known dominantly inherited cancer syndromes [Familial breast (-ovarian) cancer, hereditary no-polyposis colon cancer]. However, one patient belonged to a Li-Fraumeni family, raising the possibility that testicular cancer may be an infrequent component of this rare cancer syndrome. This study supports the hypothesis that families of testicular cancer patients are not prone to cancer.     

Aspirin and cancer risk: a quantitative review to 2011

BackgroundAspirin has been associated to a reduced risk of colorectal and possibly of a few other common cancers.MethodsTo provide an up-to-date quantification of this association, we conducted a meta-analysis of all observational studies on aspirin and 12 selected cancer sites published up to September 2011.ResultsRegular aspirin is associated with a statistically significant reduced risk of colorectal cancer [summary relative risk (RR) from random effects models = 0.73, 95% confidence interval (CI) 0.67–0.79], and of other digestive tract cancers (RR = 0.61, 95% CI = 0.50–0.76, for squamous cell esophageal cancer; RR = 0.64, 95% CI = 0.52–0.78, for esophageal and gastric cardia adenocarcinoma; and RR = 0.67, 95% CI = 0.54–0.83, for gastric cancer), with somewhat stronger reductions in risk in case–control than in cohort studies. Modest inverse associations were also observed for breast (RR = 0.90, 95% CI = 0.85–0.95) and prostate cancer (RR = 0.90, 95% CI = 0.85–0.96), while lung cancer was significantly reduced in case–control studies (0.73, 95% CI = 0.55–0.98) but not in cohort ones (RR = 0.98, 95% CI = 0.92–1.05). No meaningful overall associations were observed for cancers of the pancreas, endometrium, ovary, bladder, and kidney.ConclusionsObservational studies indicate a beneficial role of aspirin on colorectal and other digestive tract cancers; modest risk reductions were also observed for breast and prostate cancer. Results are, however, heterogeneous across studies and dose–risk and duration–risk relationships are still unclear.