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Risk of prostate, ovarian, and endometrial cancer among relatives of women with breast cancer.

OBJECTIVE: To investigate the risk of prostate, ovarian, and endometrial cancer among relatives of patients with breast cancer. DESIGN: Cohort study of 947 pedigrees in which the proband had breast cancer, linked with the Icelandic cancer registry. SETTING: Iceland. SUBJECTS: The 947 pedigrees included 29,725 people, of whom 1539 had breast cancer, 467 had prostate cancer, 135 ovarian cancer, and 105 endometrial cancer. MAIN OUTCOME MEASURES: Risk of prostate, ovarian, and endometrial cancer among blood relatives of women with breast cancer compared with risk in spouses. RESULTS: The risk of prostate cancer was significantly raised for all relatives (1.5), first degree relatives (1.4), and second degree relatives (1.3) of women with breast cancer. Risk of ovarian cancer was raised for all relatives (1.9) and first degree relatives (1.9) and risk of endometrial cancer was raised for all relatives only (1.9). The risk of prostate cancer was raised if the proband with breast cancer had a first degree relative with prostate cancer. CONCLUSIONS: Coaggregation exists between breast cancer and cancers of the prostate, ovaries, and endometrium. This risk relation is probably based on genes which act by increasing the risk for cancer at these sites. Environmental factors that are common among relatives may also play a part. Continued research is required into pathophysiological mechanisms that could explain these observations.

Aged↗

Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

A MESSAGE FROM ASCO's PRESIDENT For the second consecutive year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO developed this report to demonstrate the enormous progress being made on the front lines of cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and physicians, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on new targeted therapies that are improving survival and response rates in hard-to-treat cancers such as kidney cancer, HER-2-positive breast cancer, head and neck cancer, and chronic myelogenous leukemia; the FDA's approval of the world's first preventive vaccine for human papillomavirus (HPV), which has the potential to dramatically reduce the global burden of cervical cancer; and advances in the fast-growing field of personalized medicine, including a new lung cancer test that could help physicians better target treatments and predict prognosis. These advances are only part of the landscape. Survival rates are on the rise, the number of cancer deaths in the United States began declining for the first time since 1930, and new research is showing that the rates of certain common cancers, such as those of the breast and colon, have stabilized, and may have even begun to decline. However, cancer research still faces a number of major obstacles. At a time of extraordinary scientific potential, declining federal funding of cancer research threatens to stall or even reverse recent progress. Such funding cuts have already led to fewer clinical trials, fewer talented young physicians entering the field, and a growing bottleneck of basic science discoveries waiting to be "translated" into useful therapies and diagnostics. In addition to highlighting the major research advances over the past year, this report also identifies key barriers to accelerating the pace of cancer research and outlines ASCO's recommendations for overcoming them. Despite these and other challenges, there is much good news on the front lines of cancer research. This report demonstrates the essential role of clinical cancer research in finding new and better ways to treat, diagnose, and prevent a group of diseases that strike half of men and one-third of women in the United States.

Breast Neoplasms↗

Retrospective studies of gastric subserosal (ss) cancer--in comparison to pm- and se-cancers.

The deepest gastric cancer invasion into the tela subserosa is expressed as the ss-cancer. Subserosal gastric cancers (ss) can be divided into 4 subtypes; ss alpha, ss beta, (ss gamma) and ss gamma, pathologically. These four subtypes were compared to cancerous invasion into the muscularis propria (pm-cancer) and cancerous invasion with serosal exposure (se-cancer). During the 10 years from 1979 to 1988, a total of 938 cases with gastric cancer were resected in the First Department of Surgery, Kurume University Hospital. Of these, 104 (11.1%) cases were ss-cancers, consisting of 28 (27%) cases of ss alpha, 33 (32%) cases of ss beta, 4 (3%) cases of (ss gamma) and 39 (38%) cases of ss gamma. Pm-cancers and ss-cancers were most frequently observed in Borrmann type 2, macroscopically, and in the differentiated type, histologically. On the other hand, se-cancers were frequently observed in Borrmann type 3 and in an undifferentiated type. Positive lymph node metastases were found in 49.1% of pm-cancers, in 50.0% of ss-cancers and in 79.9% of se-cancers (p < 0.01), with no statistical difference in the positive lymph node metastasis rates for the subdivisions of ss-cancer. In ss-cancer, however, there was a statistical difference in prognosis according to the tumor size, and according to the degree of subserosal infiltration. The 5-year survival rate was 82.3% for pm-cancer, 75.0% for ss-cancer and 34.7% for se-cancer (p < 0.01).

Female↗

[Familial history of cancer and lung cancer].

There are many studies supporting the family history in lung cancer. In this study, we observed 1500 with lung cancer cases diagnosed between the years 1995-2000 in our clinic, and investigated family tendency of lung cancer in a control group including partners of 600 patients with family history of cancer. We conducted face-to-face interviews with 100 patients with lung cancer, and with first degree relatives of the other 1400 patients with lung cancer. There were 600 positive family history of cancer. Control populations were matches of the cancer patients with positive family history of cancer. Cases and controls were asked to report on their family history of cancer, as well as smoking status of family members. In conclusion, in 40% of 1500 patients with lung cancer, there was positive family history of lung cancer with regard to malignity. This positive family history of cancer was consisted of 51.8% lung cancer, 35.5% digestive cancer and 12.7% other cancers such as breast, larynx, prostate and bone. In control group, the value of the positive family history of lung cancer with regard to malignity was 5.0% (p< 0.001). These results support the hypothesis of a genetic susceptibility by showing that the patients with lung cancer have significantly more positive family history of lung cancer and digestive cancer.

Adult↗

Evaluating genetic association among ovarian, breast, and endometrial cancer: evidence for a breast/ovarian cancer relationship.

The possibility of a genetic relationship between ovarian, breast, and endometrial cancer was investigated in data from a large multicenter, population-based, case-control study, the Cancer and Steroid Hormone Study conducted by the Centers for Disease Control (CDC). Age-adjusted relative risks (RRs) for mothers and sisters of 493 ovarian cancer cases, 895 breast cancer cases, and 143 endometrial cancer cases versus 4,754 controls were calculated. Significantly elevated age-adjusted RRs were found for ovarian cancer (RR = 2.8; 95% confidence interval [CI] = 1.6-4.9) and breast cancer (RR = 1.6; 95% CI = 1.1-2.1) among relatives of ovarian cancer probands and for breast cancer (RR = 2.1; 95% CI = 1.7-2.5) and ovarian cancer (RR = 1.7; 95% CI = 1.0-2.0) among relatives of breast cancer probands. Relatives of endometrial cancer probands had an elevated RR for endometrial cancer only (RR = 2.7; 95% CI = 1.6-4.8). The genetic relationship between ovarian, breast, and endometrial cancer was tested using a multivariate polygenic threshold model developed by Smith (1976), which was modified to accommodate three classes of probands. Estimates of heritability for ovarian, breast, and endometrial cancer were 40%, 56%, and 52%, respectively. There was a significant genetic correlation between ovarian and breast cancer (R12 = .484). Evidence for significant genetic overlap between endometrial cancer and either ovarian or breast cancer was not found. These results suggest the existence of a familial breast/ovarian cancer syndrome. Endometrial cancer, while heritable, appears to be genetically unrelated.

Adult↗

The risk of a second primary cancer occurring in five-year survivors of an initial cancer.

Patients with a greater than five-year survival diagnosed with cancer of the stomach, colon, breast and uterus (included in situ) at the Kanagawa Cancer Center from 1963 to 1980 were studied for multiple primary cancers. They were followed up to December 31, 1985, for the occurrence of second primary cancers by means of a record linkage to the population-based cancer registry in Kanagawa Prefecture. The occurrence rate of total second primary cancers was 2.6% (76/2,977). Among the first primary cancer sites, the rate for cancer of the colon was highest: 5.3% (5/94), and the rate for women with cancer of the uterus lowest: 1.4% (16/1,146). The number of observed second primary cancers was compared with the expected number, which was calculated by the person-years method, to obtain an estimate of the risk. The relative risks (RR: observed: expected value) of women with cancer of the breast were significantly high for developing cancer of the colon (RR, 3.7), cancer of the opposite breast (RR, 3.9) and cancer of the ovary (RR, 5.8). Men with cancer of the stomach had a significant risk of developing cancer of the colon (RR, 3.3). It may be considered, at least in part, that some cancer patients, especially those with cancer of the breast, have a high risk of a second primary cancer occurring. These results may provide clues and information to the etiology of predisposition to and prevention of cancer.

Adult↗

Multiple primary cancers (MPC) associated with bladder cancer: an analysis of the clinical and autopsy cases in Japan.

Three hundred seventy-two clinical cases of multiple primary cancers (MPCs) involving bladder cancer (reported in the Japanese literature and including 36 of our own cases) and 376 autopsy cases (collected from the tables of the Annuals of Pathological Autopsy Cases in Japan from 1974 to 1981), were analyzed. Of the clinical cases studied, 299 patients were males and 73 females, and their average age was 65.7 years. In the 342 cases having only two primary cancers (PC), the two most common cancers associated with bladder cancer were cancer of the stomach (27.4%) and of the prostate (15.3%) in the males, and cancer of the cervix (27.9%) and of the stomach (16.2%) in the females. In the 119 cases in which the interval was known, the two PC were synchronous in 58 cases and metachronous in 61. In most cases of bladder cancer associated with other urological cancers (85.2%) the two were synchronous. In the females with metachronous cancers, bladder cancer frequently occurred as the second cancer after treatment of cervical or breast cancer. In autopsy cases, the ratio of MPC cases to the total number of cancer cases was 5.2%, and the ratios of MPC cases including bladder cancer to the total number of MPC cases and bladder cancer cases were 5.7% and 15.9%, respectively. The results of a study on organ association between cancer of the urinary bladder and of other organs were almost the same as those in the clinical study except for a lower frequency in other urogenital organs. In an epidemiological analysis of our own cases, the risk of MPC associated with bladder cancer was found to be highest in the stomach, the prostate, the larynx, and the liver. A significant value for the relative risk of a second cancer in another organ following bladder cancer was observed only for the prostate.

Adult↗

Second cancer following cutaneous melanoma and cancers of the brain, thyroid, connective tissue, bone, and eye in Denmark, 1943-80.

Second primary cancers were studied in persons with rare tumors between 1943 and 1980. The risk of developing a new cancer was evaluated in 7,211 persons with cutaneous melanoma, 1,784 persons with eye cancer, 10,273 persons with tumors of the brain and nervous system, 1,935 persons with thyroid cancer, 1,542 persons with bone tumors, and 2,318 persons with malignant neoplasms of the connective tissue. All cancer patients were diagnosed in Denmark between 1943 and 1980 and survived for 2 or more months. Nonmelanoma skin cancers were excluded from the analysis, whereas tumors of the brain and nervous system included both benign and malignant neoplasms. Overall, patients with these cancers showed no greater incidence of new tumors than expected from comparisons with the general population. An excess of chronic lymphocytic leukemia was observed subsequent to all cancers derived from the neural tube, i.e., melanoma and tumors of the eye, brain, and nervous system. Bone cancer occurred excessively, although the possibility of misclassified metastases could not be eliminated. Patients with tumors of the brain and nervous system who survived for 10 or more years developed significantly more cancers of the kidney and connective tissue and melanoma than anticipated. A deficit of second cancers of the digestive system was noted after primary bone and connective tissue cancers, in contrast to an excess of second cancers of the lung and kidney. Although based on few cases, patients with bone cancer showed a large excess of eye cancer as a second primary. The association between cancers of the breast and connective tissue was found to be bidirectional. Persons with connective tissue cancer were at increased risk of developing non-Hodgkin's lymphoma. Thyroid cancer patients were at high risk of subsequent tumors of the brain and nervous tissue and non-Hodgkin's lymphoma. However, contrary to previous reports, the risk of breast cancer was not elevated following thyroid cancer.

Bone Neoplasms↗

Annual report to the nation on the status of cancer, 1973-1996, with a special section on lung cancer and tobacco smoking.

BACKGROUND: The American Cancer Society, the National Cancer Institute (NCI), and the Centers for Disease Control and Prevention (CDC), including the National Center for Health Statistics (NCHS), provide the second annual report to the nation on progress in cancer prevention and control, with a special section on lung cancer and tobacco smoking. METHODS: Age-adjusted rates (using the 1970 U.S. standard population) were based on cancer incidence data from NCI and underlying cause of death data compiled by NCHS. The prevalence of tobacco use was derived from CDC surveys. Reported P values are two-sided. RESULTS: From 1990 through 1996, cancer incidence (-0.9% per year; P = .16) and cancer death (-0.6% per year; P = .001) rates for all sites combined decreased. Among the 10 leading cancer incidence sites, statistically significant decreases in incidence rates were seen in males for leukemia and cancers of the lung, colon/rectum, urinary bladder, and oral cavity and pharynx. Except for lung cancer, incidence rates for these cancers also declined in females. Among the 10 leading cancer mortality sites, statistically significant decreases in cancer death rates were seen for cancers of the male lung, female breast, the prostate, male pancreas, and male brain and, for both sexes, cancers of the colon/rectum and stomach. Age-specific analyses of lung cancer revealed that rates in males first declined at younger ages and then for each older age group successively over time; rates in females appeared to be in the early stages of following the same pattern, with rates decreasing for women aged 40-59 years. CONCLUSIONS: The declines in cancer incidence and death rates, particularly for lung cancer, are encouraging. However, unless recent upward trends in smoking among adolescents can be reversed, the lung cancer rates that are currently declining in the United States may rise again.

Adolescent↗

Established Cancer Predisposition Genes in Single and Multiple Cancer Diagnoses.

IMPORTANCE: Much of the understanding of cancer risk associated with rare pathogenic variants (RPVs) is derived from family-based studies or clinically ascertained samples, which may be limited by ascertainment and selection bias. OBJECTIVE: To quantify associations between RPVs in previously implicated cancer predisposition genes and single and multiple cancer diagnoses in a large population-based study. DESIGN, SETTING, AND PARTICIPANTS: In this genetic association study, whole-exome sequencing data were used from the UK Biobank, a UK population-based cohort that enrolled participants aged 40 to 69 years between 2006 and 2010. Participants who were involved in the whole-exome sequencing release of 200&#x202f;000 genomes in 2020 were included in this study. This analysis included White participants only, as findings in other racial and ethnic groups had small sample sizes. Participants were diagnosed before or after biobank enrollment until March 2024. EXPOSURES: The sequencing data of a set of 96 previously implicated cancer predisposition genes were analyzed and compared using 2 methods. To determine the statistical significance of an association, a robust optimal sequence kernel association test was used, while odds ratios (ORs) and 95% CIs were obtained through Firth logistic regression. MAIN OUTCOMES AND MEASURES: The primary study outcome was the diagnosis of 1 of 11 cancers (bladder, breast, central nervous system, colorectal, lung, melanoma, ovary, pancreatic, prostate, renal, thyroid) defined by relevant diagnosis codes in inpatient hospital diagnosis, cancer registry, and/or death registry data. RESULTS: Data from 183&#x202f;627 participants (101&#x202f;414 [55.2%] female) were analyzed, including 25&#x202f;824 participants with at least 1 cancer diagnosis, of whom 23&#x202f;704 (91.8%) had a single cancer diagnosis and 2130 (8.2%) had 2 or more cancer diagnoses. A total of 157&#x202f;793 controls had no cancer diagnosis. The median (IQR) age was 62 (56-65) years in participants with at least 1 cancer diagnosis, compared to 57 (50-63) years in those without a cancer diagnosis. Genetic variation in 16 genes was significantly associated with at least 1 cancer of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDKN2A, CHEK2, HOXB13, MITF, MLH1, MSH2, MSH6, NF1, PALB2, RAD51C, and RAD51D). The presence of an RPV in 1 of these 16 genes was associated with increased odds of at least 1 cancer (OR, 1.87; 95% CI, 1.76-1.98) and multiple primary cancers (OR, 2.56; 95% CI, 2.18-2.99). Carrier frequency was 6.28% and 8.36%, respectively. CONCLUSIONS AND RELEVANCE: This genetic association study demonstrates several established associations between cancer predisposition genes and cancer diagnoses in an unselected population-based study. These results also demonstrate that RPVs in cancer predisposition genes are associated with multiple primary cancer diagnoses, suggesting that multigene panel testing may be warranted in these individuals.

Humans↗

Interval cancers in the Norwegian breast cancer screening program: frequency, characteristics and use of HRT.

Breast cancers diagnosed between screening examinations among women who attend a breast cancer screening program are defined as interval cancers. The Norwegian Breast Cancer Screening Program started as a pilot project in 1996, and data from the first 2-year interval are available. Our study quantifies interval cancers in the pilot project and explores characteristics and factors that may be associated with interval cancer. Interval cancers in the screening population were identified through the Cancer Registry of Norway. The frequency of invasive interval cancer was calculated as cases per 10,000 screened and as observed/expected ratio. Characteristics of the interval cancers were compared to screening-detected and clinical cancers. Breast density was assessed in a blinded review of 3 categories of screening mammograms. Information on hormone replacement therapy (HRT) use was collected from a questionnaire. The frequency of invasive interval cancers was 18.2 (15.9-20.7) per 10,000 screened and the observed/expected ratio was 0.49 (0.43-0.56). The frequency in the second year of the interval was higher than reported from other programs. The median tumor size of the interval cancers was 19.5 mm and 44.0% of the patients had affected axillary lymph nodes. The interval cancer cases had higher proportions of dense breasts and reported use of HRT compared to screen normal and screening-detected cases. The reported frequency of interval cancers is similar to comparable programs. The interval cancers differed significantly from the cancers detected in the first screening round and were more similar to clinical cancers. Interval cancer was associated with dense breasts and use of HRT. Screening programs must keep these associations in focus.

Aged↗

Second primary cancers following cancers of the kidney and prostate in New South Wales (Australia), 1972-91.

Data from the New South Wales (NSW) (Australia) Central Cancer Registry for the period 1972-91 were examined to determine the risk of second primary cancers following an initial invasive cancer of the renal parenchyma (ICD-9 code 189.0), renal pelvis (code 189.1), or prostate (code 185). Eligible cases were restricted to those who had survived for at least two months after diagnosis of the first primary cancer. Expected numbers of cancers were obtained by assuming that subjects experienced the same cancer incidence as prevailed in the corresponding general population and applying gender-, age-, and calendar-specific rates to the appropriate person-years at risk. The relative risk (RR) of a second primary cancer was taken to be the ratio of observed to expected numbers of second cancers. Following prostatic cancer, there was an overall deficit of cancers at all sites combined (RR = 0.79, 95 percent confidence interval [CI] = 0.75-0.84), and no site had a significantly raised RR. Taking this into consideration, there appeared to be a reciprocal relationship of increased risk of prostatic cancer (RR = 1.7, CI = 1.2-2.3) following an initial cancer of the renal parenchyma and of renal parenchymal cancer (RR = 1.2, CI = 0.8-1.7) after cancer of the prostate. An increased risk of bladder cancer occurred following renal parenchymal (RR = 3.4, CI = 1.1-8.0, for women only) as well as after renal pelvic cancer (men: RR = 8.7, CI = 5.4-13; women: RR = 39, CI = 26-56). A tobacco-related pattern of excess risk was seen after renal pelvic cancer but not after cancer of the renal parenchyma. These data illustrate that an excess of second primary cancers may reflect shared etiologic factors or increased medical surveillance.

Aged↗

Histologic comparison of hereditary nonpolyposis colorectal cancer associated with MSH2 and MLH1 and colorectal cancer from the general population.

PURPOSE: Hereditary nonpolyposis colorectal cancer is reported to have special histologic features. This study compares the histologic features of hereditary nonpolyposis colorectal cancer to colorectal cancers from the general population when hereditary nonpolyposis colorectal cancer cases are restricted to families with known MSH2 and MLH1 mutations. METHODS: Thirty-seven cancers from kindreds carrying MSH2 mutations, 27 cancers from kindreds carrying MLH1 mutations, and 37 colorectal cancers from the general population were reviewed by a pathologist blinded to hereditary nonpolyposis colorectal cancer gene status. Tumor grade, growth pattern, Crohn's-like lymphoid reaction, mucin production, extent of disease in the bowel wall, and lymph node status were evaluated. RESULTS: Poor differentiation and Crohn's-like reaction were a feature of 44 and 49 percent of hereditary nonpolyposis colorectal cancer compared with 14 percent (P = 0.002) and 27 percent (P = 0.049) of colorectal cancers from the general population, respectively. There was no difference in growth pattern, mucin production, lymph node involvement, or local extent of disease between hereditary nonpolyposis colorectal cancer and colorectal cancers from the general population. Poor differentiation and lymph node metastases were found in 57 and 49 percent of MSH2 compared with 26 percent (P = 0.002) and 10 percent (P = 0.03) of MLH1-associated cancers, respectively. There was no difference in growth pattern, mucin production, Crohn's-like lymphoid reaction, or local extent of disease between subgroups of hereditary nonpolyposis colorectal cancer. CONCLUSIONS: Poor differentiation and Crohn's-like reaction are more common in hereditary nonpolyposis colorectal cancer than colorectal cancers from general population. Poor differentiation and lymph node metastases are more commonly seen in MSH2-associated cancers than MLH1. Evaluation of the natural history, pathogenesis, and prognosis of colorectal cancer in hereditary nonpolyposis colorectal cancer should include consideration of which mismatch repair genes are mutated and what the specific mutations are.

Adaptor Proteins, Signal Transducing↗

Cancer screening practices among cancer survivors.

BACKGROUND: Cancer survivors are more vulnerable to future cancers than individuals without cancer. As such, it is important to understand whether survivors are engaging in cancer screenings. METHODS: The screening practices reported in response to the 2000 Health Interview Survey of 2151 individuals with cancer were examined and compared to those of 30,195 individuals without cancer. RESULTS: The proportion of cancer survivors obtaining screenings ranged from 21% to 77%. Compared to individuals without cancer, women with cancer were more likely to have had a mammogram (odds ratio [OR]=1.8, 95% CI=1.5-2.1), a clinical breast exam (OR=2.2, 95% CI=1.9-2.5), and/or a Papanicolaou test (OR=1.3, 95% CI=1.1-1.5) in the recommended timeframe. Similarly, men with cancer were more likely than men without cancer to have had a prostate-specific antigen test performed (OR=2.5, 95% CI=2.0-3.0). All cancer survivors were more likely than individuals without a cancer diagnosis to have had a total body skin exam (OR=4.0, 95% CI=3.5-4.6), a fecal occult blood test (OR=1.4, 95% CI=1.2-1.6), and/or a colorectal exam (OR=2.2, 95% CI=1.9-2.5). Similar results were obtained when individuals diagnosed with the cancer for which the screen was designed to detect were excluded. CONCLUSIONS: The results demonstrate that cancer survivors have higher screening rates than individuals without a cancer diagnosis. Despite this, the proportion of survivors obtaining screenings varies considerably by the type of screen. An understanding of the impact of cancer screening in cancer survivors, as well as the reasons for and against obtaining cancer screenings, is necessary.

Adult↗

Radiotherapy for primary thyroid cancer as a risk factor for second primary cancers.

Although radiation is considered a risk factor for thyroid cancer, the potential relationship between radiation therapy and the risk of second primary cancer among patients with first primary thyroid cancer has not been evaluated. We identified 26,639 patients with first primary thyroid cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2000. Information on radiation therapy as well as second primary cancers was recorded in SEER. The proportional hazards model was utilized to estimate adjusted risk ratios (RRs) and their 95% confidence intervals (CIs) to assess the potential association between radiation therapy for thyroid cancer and the risk of second primary cancers. With 270,674.33 person-years of follow-up, 1,896 (7.1%) of the 26,639 patients with first primary thyroid cancer developed second primary cancers. Among the second primaries, 35 occurred in the thyroid. No obvious association was observed between radiation therapy and the overall risk of second primary cancer after ten years of follow-up (RR=1.07, 95% CI=0.88-1.30). However, an increased risk was seen for several cancers, including upper digestive system cancers (RR=1.66, 95% CI=1.07-2.57) and myeloid malignancies (RR=3.26, 95% CI=1.39-7.67). Radiation therapy was associated with reduced second cancer risks for thyroid cancer (RR=0.18, 95% CI=0.04-0.76). Beam radiation might be important to the digestive system, radioactive implants might be associated with the male genital system, radioisotopes might have an effect on myeloid malignancies, and combined beam radiation with radioactive implants or radioisotopes might be related to the increased risk of respiratory system cancers. This study suggests that radiation therapy for patients with first primary thyroid cancer might be associated with an increased risk of developing a second primary cancer in the upper digestive system and second primary myeloid malignancies. Radiation therapy for adult patients with thyroid cancer might be associated with a reduced risk of second primary thyroid cancer.

Aged↗

Impact of familial and hereditary prostate cancer on cancer specific survival after radical retropubic prostatectomy.

PURPOSE: Men with a family history of prostate cancer are at higher risk for prostate cancer. There are conflicting data regarding the impact of hereditary forms of prostate cancer on long-term outcomes after radical prostatectomy. We examined the impact of familial and hereditary prostate cancer treatment in the prostate specific antigen era. MATERIALS AND METHODS: Patients who underwent radical prostatectomy for prostate cancer from 1987 to 1997 were surveyed (3,560 responders) to determine the family history of prostate cancer. Patients were categorized as having familial prostate cancer if they had at least 1 first-degree relative with prostate cancer. Hereditary prostate cancer was defined as nuclear families with 3 cases of prostate cancer, families with prostate cancer in each of 3 generations and families with 2 men diagnosed before age 55 years. Sporadic prostate cancer was defined as patients with no family history. Clinical and pathological features, and long-term outcome measures, including biochemical recurrence-free, systemic progression-free and cancer specific survival, were compared among patients with familial, hereditary and sporadic prostate cancer. RESULTS: A total of 865 and 133 patients were categorized as having familial prostate cancer and hereditary prostate cancer, respectively. Preoperatively prostate specific antigen was higher in patients with hereditary prostate cancer than in the other 2 groups (p = 0.04). Ten-year biochemical progression-free, systemic progression-free and cancer specific survival were equivalent. CONCLUSIONS: Except for preoperative prostate specific antigen, clinicopathological features and long-term oncological outcomes are equivalent after radical prostatectomy in patients with familial, hereditary and sporadic prostate cancer.

Adult↗

Cancer in siblings of children with cancer in the Nordic countries: a population-based cohort study.

BACKGROUND: In some rare inherited disorders such as Li-Fraumeni syndrome, relatives of children with cancer are at increased risk of cancer. We aimed to assess relations between childhood cancer and sibling risk, and evaluate the influence of recessive conditions in cancer causation. METHODS: We did a population-based cohort study in the Nordic countries of 42277 siblings of 25605 children with cancer. Children with cancer were identified from records in the five Nordic cancer registries, and their siblings from nationwide population registries. Cancers in siblings were documented through record linkage with cancer registries and compared with national incidence rates. We also assessed cancer incidence in parents to identify familial cancer syndromes. FINDINGS: 284.2 cancers were expected in siblings, whereas 353 were diagnosed (standardised incidence ratio 1.24 95% CI 1.12-1.38). Risk ratios for siblings were highest in the first decade of life (2.59, 1.89-3.46). We excluded 56 families with genetic syndromes linked to cancer, which reduced this ratio from 1.7 to 1.0 (0.7-1.3) for siblings younger than 20 years, and from 1.3 to 1.0 (0.8-1.3) for those aged 20-29 years. We found no new patterns of familial cancer that indicated inherited susceptibility, or evidence that recessive conditions might contribute to cancers not explained by syndromes. 40% of cancers in siblings that occurred before age 20 years could be attributed to known genetic factors, whereas 60% remained unexplained. INTERPRETATION: Apart from rare cancer syndromes, paediatric cancer is not an indicator of increased cancer risk in siblings.

Adolescent↗

Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium.

Germline mutations in a gene on chromosome 17q known as BRCA1 are responsible for a large proportion of inherited predispositions to breast and ovarian cancer. In 33 families with evidence of linkage to BRCA1, we estimated the risks of breast and ovarian cancer from the occurrence of second cancers in individuals with breast cancer, and examined the risks of other cancers in BRCA1 carriers. 26 contralateral primary breast cancers occurring more than 3 years after a first breast cancer were observed before age 70, giving an estimated cumulative risk of breast cancer in gene carriers of 87% by age 70.23 primary ovarian cancers occurred in women with a previous breast cancer, resulting in an estimated cumulative risk of ovarian cancer of 44% by age 70.87 cancers other than breast or ovarian cancer were observed in individuals with breast or ovarian cancer and their first-degree relatives compared with 69.3 expected, based on national incidence rates. Significant excesses were observed for colon cancer (estimated relative risk [RR] to gene carriers 4.11 [95% CI 2.36-7.15]) and prostate cancer (3.33 [1.78-6.20]). No significant excesses (or deficits) were noted for cancers of other sites. Our study provides estimates of breast and ovarian cancer risks which are useful for counselling BRCA1-mutation carriers. It also shows that carriers are at increased risk of colon and prostate cancer, which may be of clinical significance in certain families if the risks are associated with specific mutations.

Adult↗