Familial aggregation of tumors and detection of hereditary non-polyposis colorectal cancer in 3-year experience of 2 population-based colorectal-cancer registries

The clinical data of 2 population-based registries, located in areas with different incidence rates of colorectal cancer, were used in order to assess the role of familial factors in the pathogenesis of these tumors. The occurrence of tumors in family members was investigated in 389 subjects with colorectal cancer registered in Modena (Northern Italy, an area characterized by a high incidence of colorectal malignancies) between 1984 and 1986; similar information was obtained in 213 patients with tumors of the large bowel registered in Ragusa (Sicily, Southern Italy, an area of similar magnitude and with low incidence rates for these tumors) in the 3-year period 1988 to 1990. In both series, colorectal cancer occurred significantly more often among relatives of patients. Controls were patients of the same sex and age (±5 years) hospitalized during the study periods, but not for gastrointestinal or neoplastic diseases. There were 89 cancer cases (3.1%) among 2,851 relatives of patients in Modena, vs. 17 cases among 1,744 relatives (1.0%) in Ragusa (p < 0.01). Apart from colorectal cancer, there was no excess of other types of tumors in patients' families (in both series). During the 3 years of registration, 17 cases of hereditary non-polyposis colorectal cancer (HNPCC, or Lynch syndrome) were diagnosed in Modena; in contrast, this syndrome was more rare in Ragusa (one case only during 3 years of observation). Similarly, many more families with clinical suspicion of HNPCC were recorded in Northern regions (44 vs. 10). Although incidence rates of colorectal cancer are appreciably higher in Northern than in Southern Italian regions, the excess of this cancer type among close relatives is similar. However, fullblown HNPCC or suspected Lynch syndrome were significantly more frequent in Northern Italy. © 1995 Wiley-Liss, Inc.     

Trends in the incidence of non-melanocytic skin cancer (NMSC) treated in Australia 1985–1995: Are primary prevention programs starting to have an effect?

Non-melanocytic skin cancer (NMSC) is the most common cancer in Australia, but data on its incidence are not routinely collected by cancer registries. National surveys were conducted in 1985, 1990 and 1995 to estimate NMSC incidence. Trends in incidence between 1985 and 1995 have been examined to determine the impact of primary prevention campaigns aimed at controlling skin cancer in Australia. National random household surveys of Australians aged over 13 years were used to estimate NMSC incidence in 1985, 1990 and 1995. Age- and sex-specific rates by survey year were modelled using Poisson regression. Basal cell carcinoma (BCC) rates in 1995 were 788 per 100,000, an increase of 19% since 1985. Squamous cell carcinoma (SCC) rates rose by 93% over the same period, from 166 to 321 per 100,000. The ratio of BCC:SCC changed from 4:1 in 1985 to 2.5:1 in 1995. BCC rates in latitudes <29°S remained at about 3 times those in latitudes >37°S over the decade. The ratio of SCC incidence between these latitudes changed from around 7:1 to 3:1 over the same period. Although NMSC incidence rates continue to rise, there have been reductions in BCC observed in younger age groups. Incidence rates of NMSC continue to rise in Australia, but there is evidence of a reduction in BCC incidence in younger cohorts. This is evidence that public health campaigns to reduce sun exposure may be having a beneficial effect on skin cancer rates. Int. J. Cancer 78:144–148, 1998.© 1998 Wiley-Liss, Inc.     

Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases

BACKGROUND: The incidence of hereditary nonpolyposis colon cancer (HNPCC) in the general population is not well defined because of the lack of large population-based studies. We characterized the incidence of HNPCC in a large, population-based cohort of colorectal cancer probands and analyzed the location of colorectal tumors. METHODS: Of the participating 1134 probands from three counties in Southern California, 907 had a negative family history of colorectal cancer and 227 had a positive family history of colorectal cancer. In addition, 11 referral case subjects with HNPCC were used to study mutation frequencies in two mismatch repair genes (MSH2 and MLH1) and microsatellite instability. All statistical tests were two-sided. RESULTS: Among the probands diagnosed in Orange County during 1994 (population-based sample, all ages), five were consistent with the Amsterdam criteria for HNPCC (0.9%; 95% confidence interval [CI] = 0. 3%-2.1%). Among probands diagnosed at less than 65 years of age-from the wider three-county area and a longer time span-16 (2.1%; 95% CI = 1.2%-3.4%) had a clinical history consistent with the Amsterdam criteria for HNPCC. Five (approximately 45%) of 11 of the referral HNPCC case subjects had a mutation in MSH2 or MLH1 and also showed microsatellite instability. The family members of case subjects with mutations tended to show an earlier age at diagnosis of HNPCC and more multiple primary cancers than those of case subjects without detectable mutations. Many of the known characteristics of HNPCC, including the presence of ureteral and endometrial cancers, were seen in both sets of families. The previously reported proximal location of colorectal tumors in HNPCC kindreds was not seen in the population-based dataset but was similar to the location reported in the referral cases. CONCLUSIONS: On the basis of our data, we believe that the prevalence of HNPCC in the general population is likely to be closer to 1% than to 5%. Furthermore, our study suggests that some previously reported characteristics of HNPCC, such as the proximal location of tumors in the syndrome, may not always hold true in a population-based sample.     

Risk of cancer among relatives of patients with glioma.

We report a population-based, retrospective study of 396 Icelandic people diagnosed with glioma in the years 1940-1995. The purpose of this study was to test whether astrocytomas, other glial tumors, other central nervous system tumors, or other cancers aggregate in families identified through glioma probands who were of Icelandic origin. Pedigrees of the 396 cases were traced by the Genetical Committee of the University of Iceland and linked to the Icelandic Cancer Registry. A total of 25,546 relatives, including 2,080 individuals with cancer were identified within these pedigrees. There was no statistically significant increase of glioma in relatives of glioma patients, nor was there any statistically significant increase in risk for other central nervous system tumors. There was no overall increase in incidence of all cancer combined, nor of specific common cancers (lung, prostate, breast, stomach, and colorectal) and uncommon cancers (melanoma and pancreas) in the relatives of glioma patients. Our results do not support the hypothesis of a familial aggregation of glioma indicative of a glioma susceptibility gene.     

Trends in breast cancer by race and ethnicity

In this article, the American Cancer Society (ACS) describes trends in incidence, mortality, and survival rates of female breast cancer in the United States by race and ethnicity. It also provides estimates of new cases and deaths and shows trends in screening mammography. The incidence and survival data derive from the National Cancer Institute's Surveillance, Epidemiology, and End Results program; mortality data are from the National Center for Health Statistics. Approximately 211,300 new cases of invasive breast cancer, 55,700 in situ cases, and 39,800 deaths are expected to occur among women in the United States in 2003. Breast cancer incidence rates have increased among women of all races combined and white women since the early 1980s. The increasing rate in white women predominantly involves small (< or = 2 cm) and localized-stage tumors, although a small increase in the incidence of regional-stage tumors and those larger than five cm occurred since the early 1990s. The incidence rate among African American women stabilized during the 1990s for all breast cancers and for localized tumors. African American women are more likely than white women to be diagnosed with large tumors and distant-stage disease. Other racial and ethnic groups have lower incidence rates than do either white or African American women. However, the proportion of disease diagnosed at advanced stage and with larger tumor size in all minorities is greater than in white persons. Death rates decreased by 2.5% per year among white women since 1990 and by 1% per year among African American women since 1991. The disparity in mortality rates between white and African American women increased progressively between 1980 and 2000, so that by 2000 the age-standardized death rate was 32% higher in African Americans. Clinicians should be aware that 63% and 29% of breast cancers are diagnosed at local- and regional-stage disease, for which the five-year relative survival rates are 97% and 79%, respectively. This information, coupled with decreasing mortality rates and improvements in treatment, may motivate women to have regular mammographic and clinical breast examinations. Continued efforts are needed to increase the availability of high-quality mammography and treatment to all segments of the population.     

中国家族性胃癌的研究

Objective: The aim of the study was to investigate the influence of gastric cancer family history in the gastric can-cer (GC) patients. Methods: Gastric cancer family histories within second degree relatives and clinicopathological features were obtained for 497 patients. Results: Of the 497 probands, 235 probands were incorporated into familial gastdc cancer (FGC) group (there were at least two GC members in the family); 262 probands were included in the non-FGC group (relatives only affected with non-GCs). Of 614 tumors in relatives, GC was the most frequent, followed by lung cancer, esophageal can-cer, hepatocellular cancer, colorectal cancer, urogenital cancer, breast cancer, and pancreatic cancer. Most affected members aggregated within first-degree relatives. The ratio of males to females in affected first-degree relatives was usually higher in male probands. Paternal history of GC was a strong risk for GC in males, while risk of GC by maternal history of GCs was increased in females. Difference in tumor histological types between the two groups was derived from an excess of diffuse GC in non-FGC male probands. The lower site was the most frequent tumor location in all subgroups. Conclusion: Distribu-tion of associated non-GCs in a family history of GC may vary with geographic areas. GC may have different genetic and/or environmental etiology in different families, and a certain subtype may be inherited in a male-influenced fashion.     

Fifty-year follow-up of cancer incidence in a historical cohort of Minnesota breast cancer families.

A family history of breast cancer is well established as a risk factor for the disease. Because family history is a dynamic rather than a static characteristic, longitudinal studies of entire families can be very instructive in quantifying the significance of risk classification. The Minnesota Breast Cancer Family Study is a historical cohort study of relatives of a consecutive series of 426 breast cancer cases (probands) identified between 1944 and 1952. The incidence of cancer and the measurement of risk factors in sisters, daughters, granddaughters, nieces, and marry-ins was determined through telephone interviews and mailed questionnaires. Ninety-eight percent of eligible families were recruited, and 93% of members participated. A total of 9073 at-risk women were studied: 56% were biological relatives of the case probands, whereas the others were related through marriage. Through 1996, 564 breast cancers were identified in nonprobands. Compared to the rate of breast cancer among marry-ins (188 cases), sisters and daughters of the probands were at a 1.9-fold greater age-adjusted risk (128 cases; 95% confidence interval, 1.4-2.4); granddaughters and nieces were at a 1.5-fold greater risk (248 cases, 95% confidence interval, 1.2-1.8). The breast cancer risk since 1952 was not distributed equally across families: although all biological relatives had a family history of breast cancer, 166 families (39%) experienced no additional cases. Most of the cases occurred among a subset of families: 21 families had 5 breast or ovarian cancers, 8 had 6, 2 had 7, and 4 had > or =8. There was no evidence of significantly increased risk for cancer at other sites, including the ovaries, cervix, uterus, colon, pancreas, stomach, or lymphatic tissue, although there was some evidence that stomach cancer in previous generations may help define the susceptible subset. These families contain four to five generations of validated occurrences of cancer, thus minimizing the uncertainty of genetic risk inherent in a disease with a late and variable age at onset. The patterns of breast cancer in these multigeneration families is consistent with the influence of autosomal dominant susceptibility in a subset, low penetrance genes in another, and purely environmental influences in the remainder.     

Incidence of malignant tumours in relatives of BRCA1 and BRCA2 germline mutation carriers

We investigated cancer incidence between 1958 and 1995 in 1873 individuals belonging to 29 consecutively identified BRCA1 and 20 BRCA2 associated families from Southern Sweden using data from parish and local tax authorities, as well as the Swedish Cancer Registry, Cause of Death Registry and Census Registry. 150 malignant tumours were analysed from 1145 relatives in the BRCA1 families and 87 tumours were analysed from 728 relatives in the BRCA2 families. After excluding index cases which led to the mutation analysis, the incidence for all malignant tumours was significantly increased for both BRCA1- standardised morbidity rate, SMR, 1.98, 95% confidence interval (CI) 1.59-2.45; P < 0.0001 and BRCA2- (SMR 1.79, 95% CI 1.35-2.31; P < 0.0001) associated family members. For women in BRCA1-associated families, the incidence of breast cancer (SMR 3.76, 95% CI 2.29-5.80, P < 0.0001), ovarian cancer (SMR 15.49, 95% CI 9.46-23.92, P < 0.0001), stomach cancer (SMR 5.86, 95% CI 1.60-15.01, P = 0.005) were significantly increased. Amongst men only invasive squamous cell cancer of the skin was significantly increased (SMR 6.02, 95% CI 1.96-14.05, P = 0.002). In BRCA2 associated families, female breast cancer (SMR 3.03, 95% CI 1.61-5.18, P = 0.0005) was increased after exclusion of index cases. If these were included, ovarian cancer (SMR 5.16, 95% CI 1.89-11.24, P = 0.001), invasive cervical cancer (SMR 4.21, 95% CI 1.15-10.79, P = 0.016), male breast cancer (SMR 290.52, 95% CI 125.42-572.43, P < 0.0001), and prostate cancer (SMR 2.21, 95% CI 0.89-4.56, P = 0.042) were significantly increased. The increased risk for ovarian cancer in BRCA2 related families were limited to the cases leading to mutation analysis. Our data suggest that apart from breast and ovarian cancer, the incidence of other cancer types do not appear to be greatly increased in BRCA1- and BRCA2-associated families and does not warrant specific clinical follow-up in carriers.     

Risk of ovarian cancer in BRCA1 and BRCA2 mutation-negative hereditary breast cancer families

Women from site-specific hereditary breast cancer families who carry a BRCA1 or BRCA2 mutation are at increased risk for ovarian cancer. It is less clear, however, whether individuals from hereditary breast cancer families who do not carry such a mutation are also at increased ovarian cancer risk. To determine whether women from BRCA mutation-negative hereditary breast cancer families are at increased risk for ovarian cancer, 199 probands from BRCA mutation-negative, site-specific breast cancer kindreds who consented to prospective follow-up at the time of genetic testing were identified. The incidence of new breast and ovarian cancers in probands and their families since receipt of their genetic test results was determined by questionnaire. The expected number of cancers and standardized incidence ratios (SIRs) were determined from age-specific cancer incidence rates from the Surveillance, Epidemiology, and End Results (SEER) program by using the method of Byar. All statistical tests were two-sided. During 2534 women-years of follow-up in 165 kindreds, 19 new cases of breast cancer were diagnosed, whereas only 6.07 were expected (SIR = 3.13, 95% confidence interval [CI] = 1.88 to 4.89; P < .001), and one case of ovarian cancer was diagnosed, whereas only 0.66 was expected (SIR = 1.52, 95% CI = 0.02 to 8.46; P = .48). These results suggest that women from BRCA mutation-negative, site-specific breast cancer families are not at increased risk for ovarian cancer.     

Evidence of tumor microsatellite instability in gastric cancer with familial aggregation

About 90% of gastric cancer (GC) cases appear in a sporadic setting. Nonetheless, in high incidence areas high familial aggregation rates have been recently described. Microsatellite instability (MSI) is thought to be an important molecular phenotype both in sporadic GC and in tumors of the HNPCC spectrum. The aim of this study was to assess the frequency of MSI in GC with familial aggregation. Five quasimonomorphic mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21 and NR-27) were analyzed in 250 GC patients. Seventy-five patients (30%) had at least one-first-degree family member affected by GC and 63 patients (25.2%) showed MSI. The frequency of MSI was significantly higher in patients with a positive family history of GC (38.7%) compared to patients with other tumor types within the family (15.7%) or with a negative oncological familial history (21.9%, P = 0.004). Within cases with a positive familial oncological history, the MSI frequency in families with GC only was similar to the one observed in families with GC and colon cancer (P = 0.96). Nonetheless, in families with GC and lung cancer, the frequency of MSI was significantly lower (5.6%, P = 0.007). MSI occurs in GCs with familial aggregation. Similar MSI rates have been observed in GC patients with other family members affected by GC or colon cancer. The same does not occur in families with other members affected by lung cancer. Our data seem to suggest that familial aggregation for either GC alone or gastric and colon cancer share common etiological factors in contrast to families with gastric and lung cancers. C. Pedrazzani and G. Corso are contributed equally.     

Familial gastric cancer: clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations.

Gastric cancer frequently occurs in family members with hereditary non-polyposis colorectal cancer (HNPCC) and Li-Fraumeni syndrome (LFS) and germline E-cadherin mutations were recently identified in a subset of familial gastric cancers. Thus, families with an aggregation of gastric cancers were recruited by reviewing the genealogical trees of 3632 patients with gastric cancer. The criteria for recruiting such families were the following: at least three relatives should have gastric cancer and one of them should be a first degree relative of the other two; at least two successive generations should be affected; in one of the relatives gastric cancer should be diagnosed before age 50. Thirty-one cases (0.9%) fitted all three of these criteria. There were only gastric cancer patients in 18 of the 31 families and there were no families that fitted clinical criteria of HNPCC or LFS. Paraffin-embedded tissues were available in 29 probands and DNA was successfully isolated for molecular analyses in 13 probands. RER phenotype was detected in three (23%) cases, whereas germline p53 mutations were detected in none of 13 cases. A germline E-cadherin mutation was detected in one of three diffuse types and none of 10 intestinal types, however, a mutation resulting in the replacement of Gly by Val was detected in the precursor sequence. Thus, although familial clustering of gastric cancer occurs in approximately 1% of gastric cancer patients, germline mutations of the DNA mismatch repair, p53 and E-cadherin genes do not significantly contribute to such a clustering.     

Familial Aggregation of Cancer from Proband Cases with Childhood Adrenal Cortical Carcinoma1

Family pedigree of Li-Fraumeni syndrome was investigated from probands with childhood adrenocortical carcinoma in Japan. From 47 probands, 7 families had 3 or more cancer cases at ages less than 45 years within the first generation; one satisfied Li's original criteria, two were acceptable because of multiple primary cancer in the probands, and others showed an aggregation of cancers with onsets at early ages, though no sarcoma of mesenchymal origin was found. A significantly higher occurrence of cancer in the mothers of the probands, especially of the breast, was consistent with reports from the USA, and liver cancer, osteosarcoma and lung cancer among family members under the age of 45 also showed a higher frequency than in the general population. Similarities and differences between Japanese and Caucasian cases are discussed.     

Colon Cancer Family Registry: an international resource for studies of the genetic epidemiology of colon cancer.

BACKGROUND: Family studies have served as a cornerstone of genetic research on colorectal cancer. MATERIALS AND METHODS: The Colorectal Cancer Family Registry (Colon CFR) is an international consortium of six centers in North America and Australia formed as a resource to support studies on the etiology, prevention, and clinical management of colorectal cancer. Differences in design and sampling schemes ensures a resource that covers the continuum of disease risk. Two separate recruitment strategies identified colorectal cancer cases: population-based (incident case probands identified by cancer registries; all six centers) and clinic-based (families with multiple cases of colorectal cancer presenting at cancer family clinics; three centers). At this time, the Colon CFR is in year 10 with the second phase of enrollment nearly complete. In phase I recruitment (1998-2002), population-based sampling ranged from all incident cases of colorectal cancer to a subsample based on age at diagnosis and/or family cancer history. During phase II (2002-2007), population-based recruitment targeted cases diagnosed before the age of 50 years are more likely attributable to genetic factors. Standardized protocols were used to collect information regarding family cancer history and colorectal cancer risk factors, and biospecimens were obtained to assess microsatellite instability (MSI) status, expression of mismatch repair proteins, and other molecular and genetic processes. RESULTS: Of the 8,369 case probands enrolled to date, 2,602 reported having one or more colorectal cancer-affected relatives and 799 met the Amsterdam I criteria for Lynch syndrome. A large number of affected (1,324) and unaffected (19,816) relatives were enrolled, as were population-based (4,108) and spouse (983) controls. To date, 91% of case probands provided blood (or, for a few, buccal cell) samples and 75% provided tumor tissue. For a selected sample of high-risk subjects, lymphocytes have been immortalized. Nearly 600 case probands had more than two affected colorectal cancer relatives, and 800 meeting the Amsterdam I criteria and 128, the Amsterdam II criteria. MSI testing for 10 markers was attempted on all obtained tumors. Of the 4,011 tumors collected in phase I that were successfully tested, 16% were MSI-high, 12% were MSI-low, and 72% were microsatellite stable. Tumor tissues from clinic-based cases were twice as likely as population-based cases to be MSI-high (34% versus 17%). Seventeen percent of phase I proband tumors and 24% of phase II proband tumors had some loss of mismatch repair protein, with the prevalence depending on sampling. Active follow-up to update personal and family histories, new neoplasms, and deaths in probands and relatives is nearly complete. CONCLUSIONS: The Colon CFR supports an evolving research program that is broad and interdisciplinary. The greater scientific community has access to this large and well-characterized resource for studies of colorectal cancer.     

Familial aggregation of cancer from proband cases with childhood adrenal cortical carcinoma

Family pedigree of Li-Fraumeni syndrome was investigated from probands with childhood adrenocortical carcinoma in Japan. From 47 probands, 7 families had 3 or more cancer cases at ages less than 45 years within the first generation; one satisfied Li's original criteria, two were acceptable because of multiple primary cancer in the probands, and others showed an aggregation of cancers with onsets at early ages, though no sarcoma of mesenchymal origin was found. A significantly higher occurrence of cancer in the mothers of the probands, especially of the breast, was consistent with reports from the USA, and liver cancer, osteosarcoma and lung cancer among family members under the age of 45 also showed a higher frequency than in the general population. Similarities and differences between Japanese and Caucasian cases are discussed.     

Parental Cancer as a Risk Factor for Brain Tumors (Sweden)

Objective: We used the nationwide Swedish Family-Cancer Database to analyze the risk for adult (15–61 years) brain tumors in offspring through parental cancer probands. Additionally, cancer risks were assessed among siblings of brain tumor probands. Methods: In offspring and parents, respectively, 5425 and 20,938 cases of brain tumors were diagnosed between the years 1958 and 1996. Groups of offspring were compared by calculating standardized incidence ratios (SIRs) for brain tumors. Results: Of brain tumor patients, 2.1% had a parent with nervous system cancer; SIRs were 1.7, 2.4, and 2.5 for all brain tumors, astrocytomas, and meningiomas, respectively. Parental endometrial cancer and melanoma were associated with offspring astrocytoma, and parental breast and thyroid cancers with offspring ependymoma and neurinoma, respectively. SIR for sibling nervous system tumors from brain tumor probands was not increased overall but was 2.5 in those diagnosed at ages 15–34 years. Conclusion: These data show a familial risk for brain tumors among adults.     

Germline mutation and large deletion analysis of the CDKN2A and ARF genes in families with multiple melanoma or an aggregation of malignant melanoma and breast cancer

The CDKN2A/ARF genes have been associated with increased risk of malignant melanoma (MM) in families with multiple members affected by disease and in families characterized by the constellation of breast cancer and MM. The exact contribution of CDKN2A/ARF to disease risk remains poorly characterized, especially in diverse populations. In this report, the contribution of CDKN2A/ARF germline mutations and large rearrangements to disease in Polish familial MM (FMM) and aggregations of breast cancer and MM were assessed using a strategy that included genomic sequencing, restriction fragment length polymorphism and multiplex ligation-dependent probe amplification. We examined 16 FMM cases (group 1), 44 MM probands with a cancer family aggregation (CFA) that included at least one breast cancer (group 2) and 22 breast cancer probands with CFA and MM (group 3). The results revealed a paucity of mutations in CDKN2A/ARF, suggesting that in the Polish population this gene does not contribute significantly to either FMM or MM within the context of CFA.     

河南省林州市人群胃癌的现时生存分析

目的:分析1988-2004年河南省林州市人群胃癌的生存率及不同时期的变化,评估当地胃癌二级预防及临床诊治的水平.方法:从林州市肿瘤登记处提取1988-2004年全部的胃癌发病和死亡个案记录,剔除重复和仅有死亡证明书(death certificate only, DCO)的病例.计算该地区的去肿瘤死因寿命表,并与胃癌发病死亡数据相链接.采用现时生存分析(period survival analysis)方法计算1990-1994年、1995-1999年和2000-2004年这3个时期的胃癌5年观察生存率和相对生存率,并绘制相对生存曲线.结果:林州市3个时期的胃癌5年相对生存率分别为26.66%、32.01%和40.43%,呈逐年上升趋势.男性患者的生存率要高于女性.前2个时期的贲门癌生存率要高于非贲门胃癌,而在2000-2004年则低于非贲门胃癌.结论:林州市人群胃癌生存率自20世纪90年代起逐渐提高,反映了当地胃癌二级预防及临床诊疗水平的不断提高.     

Breast cancer in New South Wales in 1972-1995: tumor size and the impact of mammographic screening.

To examine the use of mammographic screening in women in New South Wales (NSW), we measured uptake of initial mammograms and estimated the proportions of breast cancers that were screen detected. To see if mammographic screening has been associated with reductions in advanced breast cancers and mortality from breast cancer, we analyzed trends in age-specific and age-standardized breast cancer incidence and mortality from 1972 to 1995 and tumor size in 1986, 1989, 1992 and April to September 1995. Between 1984 and the end of 1995, an estimated 72% of NSW women in their 50s and 67% in their 60s had had at least 1 mammogram and, in 1995, an estimated 39% of invasive breast cancers in women in these age groups were detected by mammography. Before 1989, breast cancer incidence increased only slightly (+1.3% annually) but then, from 1990 to 1995, increased more rapidly (+3.1% annually). Between 1986 and 1995, rates of small cancers (< 1 cm) increased steeply by 2.7 times in women 40-49 years of age and 5.6 times in women 50-69 years of age. The incidence of large breast cancers (3+ cm), after little apparent change to 1992, fell by 17% in women 40-49 years of age and 20% in those 50-69 years of age to 1995. Breast cancer mortality increased slightly between 1972 and 1989 (+0.5% annually) but then fell (-2.3% annually) from 1990 to 1995. We concluded that breast cancer rates had been influenced in expected directions by the introduction of mammographic screening in women resident in NSW. We expect that recent falls in incidence of larger breast cancers and breast cancer mortality will become steeper as screening coverage increases in the second half of the 1990s.     

Cancer morbidity of the large intestine and its prognosis in the Moldavian SSR

Colorectal cancer ranks fifth in general cancer morbidity in the Moldavian SSR and second among digestive tumors. Within 1970-1979, the morbidity rate for rectal cancer increased 2.2-fold (from 3.0 to 6.70/0000), cancer of the colon--1.4-fold (from 4.4 to 6.00/0000). Rectal cancer morbidity showed a 4.30/0000 rise in male patients, matched by a 3.20/0000 rise in females. The colonic cancer morbidity rates increased by 1.5 and 1.80/0000, respectively. The results of the analysis of the said indexes suggest that by 1990 the rectal cancer morbidity rate will have reached 8.9 +/- 1.1 and colonic cancer--7.3 +/- 2.40/0000. By 1990, the rate of morbidity for cancer of the large bowel will have surpassed that for stomach cancer and it will rank first among tumors of the digestive tract should the present-day trends of morbidity remain unchanged.     

Breast and other cancers in 1445 blood relatives of 75 Nordic patients with ataxia telangiectasia

Epidemiological studies have consistently shown elevated rates of breast cancer among female blood relatives of patients with ataxia telangiectasia (AT), a rare autosomal recessive disease. A large proportion of the members of AT families are carriers of AT-causing gene mutations in ATM (Ataxia Telangiectasia Mutated), and it has been hypothesised that these otherwise healthy carriers are predisposed to breast cancer. This is an extended and enlarged follow-up study of cancer incidence in blood relatives of 75 patients with verified AT in 66 Nordic families. Blood relatives were identified through population registry linkages, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. The ATM mutation carrier probabilities of relatives were assigned from the combined information on location in family, consanguinity, if any, and supplementary carrier screening in some families. Among the 1445 blood relatives of AT patients, 225 cancers were observed, with 170.4 expected, yielding a standardised incidence ratio (SIR) of 1.3 (95% confidence interval (CI), 1.1-1.4). Invasive breast cancer occurred in 34 female relatives (SIR, 1.7; 95% CI, 1.2-2.4) and was diagnosed in 21 women before the age of 55 years (SIR, 2.9; 95% CI, 1.8-4.5), including seven mothers of probands (SIR, 8.1; 95% CI, 3.3-17). When the group of mothers was excluded, no clear relationship was observed between the allocated mutation carrier probability of each family member and the extent of breast cancer risk. We concluded that the increased risk for female breast cancer seen in 66 Nordic AT families appeared to be restricted to women under the age of 55 years and was due mainly to a very high risk in the group of mothers. The findings of breast cancer risk in mothers, but not other likely mutation carriers, in this and other studies raises questions about the hypothesis of a simple causal relationship with ATM heterozygosity.