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Breast cancer, birth cohorts, and Epstein-Barr virus: methodological issues in exploring the "hygiene hypothesis" in relation to breast cancer, Hodgkin's disease, and stomach cancer.

To address methodological issues in exploring a variant of the "hygiene hypothesis" that posits delayed infection by Epstein-Barr virus contributes to rising rates of breast cancer and Hodgkin's disease, we examined birth cohort trends in the incidence of both cancers plus stomach cancer, building on previously reported year-of-diagnosis cross-sectional associations of age-standardized rates. Using published data from the United States Connecticut state cancer registry (1935-1998) for women for each cancer site, we obtained age-specific incidence rates by birth cohort (1870-1874 to 1970-1974), along with age-standardized incidence rates for selected calendar years (1935-1939, 1940-1944,., 1990-1994, 1995-1998). Clear secular trends in incidence rates, in the opposite direction, were evident for: (a) breast cancer and for Hodgkin's disease in young adults (increasing), and (b) stomach cancer (decreasing). Correlations between the incidence of breast cancer among women ages 50-54 and Hodgkin's disease among young adults (ages 20-24) were stronger for birth cohort (Pearson correlation, 0.85) than for cross-sectional analyses (Pearson correlation, 0.68). Stronger associations between the incidence of breast cancer and non-Hodgkin's disease were evident for birth cohort compared with cross-sectional analyses, findings consonant with (but not "proof" of) the hygiene hypothesis. One methodological implication is that tests of the hygiene hypothesis must take into account birth cohort effects and age at incidence of the outcomes under study; age-standardized cross-sectional analyses may be misleading.

Adolescent↗

An evaluation of serum microelement concentrations in lung cancer and matched non-cancer patients to determine the risk of developing lung cancer: a preliminary study.

In a case-control study to determine the risk of developing lung cancer, the serum levels of vitamins A and E, carotene and selenium were determined in 31 patients, newly diagnosed as having lung cancer, and in matched controls, the said controls being selected from outpatients with no cancer. A significant, inverse association was found between serum vitamins A and E and lung cancer. The relative risk for the low vs high tertiles were, respectively, 5.94 for serum vitamin A and 8.44 for serum vitamin E. Taking histological cancer subtype into account, no relation was revealed between the microelements and squamous cell carcinoma of the lung. The relative risk for lung cancer was 6.50, however, when three, or all four, microelement levels were in the lowest tertile, compared with there being fewer than three in the lowest tertile. Even when three microelements, excluding vitamin E which had the most significant inverse association with lung cancer, were considered, the relative risk was 7.50 when any two or all three were in the lowest tertile, compared with there being just one microelement or none at all in the lowest tertile. A combined effect of vitamins A and E, carotene and selenium on the development of lung cancer has, therefore, been suggested. Further studies will thus be necessary to elucidate the cumulative effect of the serum micronutrients and trace elements, as well as the effect of single elements, on the development of lung cancer.

Adenocarcinoma↗

[Hereditary predisposition of colorectal cancer and prevalence of hereditary nonpolyposis colorectal cancer in general population of colorectal cancer patients in China].

OBJECTIVE: To analyze hereditary predisposition of CRC and the prevalence of HNPCC in general population of CRC patients in China. METHODS: CRC patients were from two sources. One is that we consecutively investigated 594 patients by ourselves. They were proved to be colorectal cancer by histology. The following data of all patients should be registered: sex, age diagnosed colorectal cancer, site, number and histological type of primary cancer. The other was the published Chinese and foreign literatures related to Chinese HNPCC prevalence, and there were cumulatively 3596 patients in all. Hereditary predisposition of CRC (or malignant tumors) is that CRC patients have two or more first- or second-degree relatives (or both) with CRC (or malignant tumors). HNPCC was diagnosed by Amsterdam Criteria I (AC I) or Amsterdam Criteria II (AC II), Japanese Criteria of HNPCC (JC). RESULTS: Hereditary predisposition of both malignant tumors and CRC were 17.2% and 5.2% in 594 patients with CRC, respectively. Multiple primary cancers and multiple CRC were 13.1% and 10.1% , respectively. Among them, multiple primary cancers and multiple CRCs without familial history were 9.1% and 6.7%, respectively. There was a correlation between familial history of malignant tumors and multiple primary cancers and multiple CRCs (both P < 0.01). Patients with familial history of malignant tumors had more frequently multiple primary cancers and multiple CRCs than patients without history of malignant tumors. Younger patients (< or = 50) were 21.4% in all CRC patients. there was a correlation between younger patients (< or =50) and familial history of malignant tumors and familial history of CRC (both P < 0.05). When CRC was diagnosed, patients with familial history of malignant tumors and familial history were younger than patients without them. In the population of CRC patients in China, prevalence of HNPCC diagnosed AC I, AC II and JC were 1.24%, 2.15% and 2.93%, respectively. CONCLUSIONS: Hereditary predispositions of malignant tumors and CRC were 17.2% and 5.2% in CRC patients, respectively. Familial history of malignant tumors, multiple primary cancers and younger patients with CRC (< or =50) were the clinical markers of hereditary predisposition of malignant tumors including CRC. Multiple primary cancers and younger patients with CRC (< or =50) were all correlated with familial history of malignant tumors. The prevalence of HNPCC in China was similar to that in Western countries.

Adult↗

Interrelation between Western type cancers and non-Western type cancers as regards their risk variations in time and space. I. Mathematical linkage among multiple cancer incidences.

The present study attempted to clarify the interrelation between multiple cancer risks by comparatively investigating the age-adjusted incidence rates (AAIR) of 8 neoplasias in 20 selected populations of the world for the last 20 years. Cancers of the stomach (for both sexes) and uterine cervix were on the decline in their incidences, and cancers of the colon (for both sexes), lung (for both sexes), breast and endometrium were on the rise in the period 1960 to 1980. Cancers of the esophagus (for both sexes) and ovary exhibited little change in their incidences during this period. A negative linear relationship was detected between the log-transformed AAIR of an increasing (Western type) cancer and that of a decreasing (non-Western type) cancer, and a positive linear relationship was detected between 2 increasing or 2 decreasing cancers regarding the log-transformed AAIR. Mathematical evidence is presented to indicate that the sum of AAIRs of both increasing and decreasing cancers can be minimized within the frame of a competitive relationship. The results obtained are discussed from the view point of cancer etiology.

Female↗

Update in cancer chemotherapy: genitourinary tract cancer, Part 5: Ovarian cancer.

An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series: included are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 5 is a review of treatments for cancer of the ovary.Ovarian cancer is the leading cause of gynecologic cancer deaths and the fourth most frequent cause of death from cancer in women in the United States. Ovarian carcinoma is a classical "hidden" neoplasm of the abdomen and, as such, is insidious in its onset. Combination chemotherapy and cytoreductive surgery, however, have provided improved survival for patients with ovarian cancer. As dosage schedules and other refinements are made, the overall outlook for patients with ovarian cancer is promising.

Adenocarcinoma↗

[Malignant transformation of thyroid cancer; poorly differentiated cancer and anaplastic cancer transformation].

The prognosis of thyroid cancer depends largely on histological differentiation and clinical stage. The prognosis in anaplastic cancer is worst, in well differentiated cancer it is best; poorly differentiated cancer takes a middle position. The prognosis of patients with differentiated cancer is generally good, however, there are cases with malignant transformation such as poorly differentiated, anaplastic and squamous-cell cancer transformation. We studied the frequency and the inducement factors of malignant transformation in patients with thyroid cancer. The frequency of poorly differentiated, anaplastic and squamous-cell cancer transformation was 13.6%, 6.4% and 0.7%, respectively. In anaplastic cancer transformation, irradiation is an important factor.

Adult↗

Endometrial cancer after tamoxifen treatment: a descriptive study of 25 breast cancer patients who subsequently developed endometrial cancer.

The aim of this study was to determine whether tamoxifen affects the histopathological features and clinical outcome of endometrial cancer occurring after breast cancer. 25 patients with a history of breast cancer who subsequently developed endometrial cancer were identified by computer assisted linkage of the Lainz Medical Center Tumor Registry with the National Austrian Cancer Registry. 8 endometrial cancers were tamoxifen-associated, whereas 17 cases were not. The median time of tamoxifen use was 32 months, with a median cumulative tamoxifen dose of 27 g. Detailed histopathological data did not show substantial difference between the two groups. The distribution by stage (FIGO) in the tamoxifen group was Stage I, 7 (87.5) with 1 patient unstaged (12.5%); and Stage I, 13 (76%), II, 2 (12%) and, stage III 2 (12%) for the non-tamoxifen users. No risk of high-grade endometrial lesions with a poor prognosis was found. The only suggestion of a difference was a trend for the mean interval between detection of breast and endometrial cancer to be shorter in the tamoxifen group (50.5 vs. 88.1 months p = 0.07). The conclusion to be drawn from this study appears to be that endometrial cancers occurring after tamoxifen exposure are of the same tumor type. Due to the small number of cases described we were not able to disprove the hypothesis that tamoxifen associated tumors were different in terms of clinical outcome and survival. Regular gynecological examinations are recommended for all breast cancer patients.

Aged↗

[Contribution of cancer registries to the evaluation of cancer treatment: on the example of rectal cancer].

Improvement of health care policy requires an assessment of health care practices. In France, morbidity registries might be the best tool for such an assessment. This study shows how the treatment of rectal cancer can be assessed by French cancer registries. Two studies were conducted: a cross-sectional study on data from 7 cancer registries in 1990 and a longitudinal study on data from 2 digestive cancer registries (departments of Calvados and Côte d'Or) between 1978 and 1990. Finally, we conducted a regional audit concerning quality control in rectal resection for cancer in Lower Normandy between 1988 and 1993. In 1990 the mean resection rate was 77.8%. The sphincter preservation rate was also significantly increased to 53.9% in 1990. The use of adjuvant radiotherapy significantly increased between 1978 and 1990, more rapidly in university centres. In more recent years, the use of radiotherapy concerned 50% of resected rectal cancers with no differences between the various types of health care centres. However, in 1990, major geographical variations were observed for the use of adjuvant radiotherapy. Similar geographical variations were observed for the use of chemotherapy which did not increase with time. Rectal cancers were not diagnosed earlier from 1978 to 1990 in the two departments of Calvados and Côte d'Or. The use of reproducible quality criteria (length of distal excision, number of nodes examined and histological status of lateral margins) showed a global deficiency and marked variations between the various types of health care centres and levels of surgical training. The french network of French cancer registries (FRANCIM) provides accurate and reliable knowledge on medical practices, geographical variations, trends and quality control. The potential of cancer registries has not been clearly determined, although such information is required to plan health care policy.

Cross-Sectional Studies↗

Report of a panel on the relationship between public exposure to pesticides and cancer. Ad Hoc Panel on Pesticides and Cancer. National Cancer Institute of Canada.

BACKGROUND: Pesticides, which by their nature are biologically active compounds, continue to raise public concern regarding their possible role as important etiologic agents in the development of human cancer. METHODS: To examine this potential role, the National Cancer Institute of Canada convened an Ad Hoc Panel on Pesticides and Cancer to examine the possible contribution of pesticide exposure, particularly in the general population, to the development of human cancer. RESULTS: The Panel focused primarily on exposure in the general population and reviewed a range of studies that addressed issues related to dietary exposure as well as incidental home and garden uses. In addition, the Panel examined the regulatory framework that exists to safeguard the public from potentially carcinogenic pesticides and also reviewed some potential benefits of pesticide use, including the availability of an abundant and low cost supply of fresh fruits and vegetables as an important strategy in the overall mitigation of cancer risk. CONCLUSIONS: The Panel concluded that it was not aware of any definitive evidence to suggest that synthetic pesticides contribute significantly to overall cancer mortality. The Panel also concluded that it did not believe that any increased intake of pesticide residues associated with increased intake of fruits and vegetables poses any increased risk of cancer. The Panel further concluded, among other things, that tobacco use continues to be the most important preventable cause of cancer and premature mortality and thus is an appropriate focus for cancer control strategy.

Environmental Exposure↗

Characteristics of prostate cancer detected in the American Cancer Society-National Prostate Cancer Detection Project.

The American Cancer Society-National Prostate Cancer Detection Project is a prospective, comparative study of a cohort of 2,999 men 55 to 70 years old not suspected on entry of having prostate cancer. A total of 164 prostate cancers is available from this project for analysis. A small proportion of tumors detected were advanced in terms of the clinical stage at diagnosis. Cancer detected by digital rectal examination tended to be more advanced than that found on the basis of only transrectal ultrasound or prostate specific antigen (PSA). A large proportion of patients received curative therapy involving radical prostatectomy in 67.1% and radiotherapy in 18.3%. Of 103 men presumed to have organ confined disease and treated by prostatectomy 64 (37.9%) actually had locally extensive cancer pathologically. PSA level and PSA density were associated with the detection of organ confined cancer but several advanced tumors had PSA levels in the normal range. Age referenced PSA, compared to conventional standards, demonstrated lower sensitivity to cancer with little improvement in specificity. The disease resulting from this multimodality detection effort represented a spectrum of pathological conditions. Further followup and evaluation are needed to determine whether these benefits are reflected in long-term mortality and survival experience.

Aged↗

Alcohol, folate, methionine, and risk of incident breast cancer in the American Cancer Society Cancer Prevention Study II Nutrition Cohort.

Recent studies suggest that the increased risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake. We examined this question among 66,561 postmenopausal women in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. A total of 1,303 incident cases had accrued during the first 5 years of follow-up. Cox proportional hazards models and stratified analysis were used to examine the relationship between alcohol, dietary and total folate intake, multivitamin use, dietary methionine, and breast cancer. We observed an increasing risk of breast cancer with increasing alcohol consumption (P for trend = 0.01). In the highest category of consumption (15 or more grams of ethanol/day), the risk of breast cancer was 1.26 (95% confidence interval, 1.04-1.53) compared with nonusers. We observed this association with higher alcohol consumption for in situ, localized, and regional disease. We found no association between risk of breast cancer and dietary folate, total folate, multivitamin use, or methionine intake. Furthermore, we found no evidence of an interaction between levels of dietary folate (P for interaction = 0.10) or total folate (P for interaction = 0.61) and alcohol. Nor did we find evidence of an interaction between alcohol consumption and recent or long-term multivitamin use (P for interaction = 0.27). Our results are consistent with a positive association with alcohol but do not support an association with folate or methionine intake or an interaction between folate and alcohol intake on risk of breast cancer.

Adult↗

The sarcoma, breast cancer, lung cancer, and adrenocortical carcinoma syndrome revisited. Childhood cancer.

We studied two children who had rhabdomyosarcoma and glioblastoma and who were from a family with a hereditary cancer syndrome that was characterized by sarcoma, breast cancer, brain tumors, lung cancer, laryngeal carcinoma, leukemia, and adrenocortical carcinoma. The deleterious genotype has now been expressed through the fourth generation of this large kindred. The pedigree emphasizes the need for an extended history of several generations to arrive at a hereditary-syndrome diagnosis. A limited pedigree may result in nonappreciation of the genetic component. The pedigree illustrates that, in certain circumstances, the highly specific varieties of cancer may occur in children before it is expressed in the parent who carries the putative gene. Pediatricians, in evaluating the causes of childhood cancer, must be cognizant of cancer among adult relatives, since this recognition may aid in the diagnosis of those hereditary cancer syndromes that are characterized by cancer occurrence in children as well as adults.

Adrenal Cortex Neoplasms↗

The cancer screening practices of adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

BACKGROUND: The current study characterized the self-reported cancer screening practices of adult survivors of childhood cancer. METHODS: A cohort of 9434 long-term survivors of childhood cancer and a comparison group of 2667 siblings completed a 289-item survey that included items regarding cancer-screening practices. RESULTS: Overall, 27.3% of female respondents reported performing breast self-examination (BSE) regularly, 78.2% reported undergoing a Papanicolaou smear within the previous 3 years, 62.4% underwent a clinical breast examination (CBE) within the last year, and 20.9% had gotten a mammogram at least once in their lifetime. Approximately 17.4% of male respondents reported performing regular testicular self-examination (TSE). Women age > or =30 years who had been exposed to chest or mantle radiation therapy were more likely to report undergoing CBE (odds ratio [OR], 1.59; 95% confidence interval [95% CI], 1.32-1.92) and mammography (OR, 1.92; 95% CI, 1.47-2.56). Compared with the sibling comparison group, survivors demonstrated an increased likelihood of performing TSE (OR, 1.52; 95% CI, 1.22-1.85) or BSE (OR, 1.30; 95% CI, 1.10-1.52), of having undergone a CBE within the last year (OR, 1.18; 95% CI, 1.02-1.35), and of ever having undergone a mammogram (OR, 1.82; 95% CI, 1.52-2.17). CONCLUSIONS: The results of the current study demonstrate that the cancer screening practices among survivors of childhood cancer are below optimal levels. Primary care physicians who include childhood cancer survivors among their patients could benefit these individuals by informing them about future cancer risks and recommending appropriate evidence-based screening.

Adult↗

Cancer risks in women with 2 breast or ovarian cancers: clues to genetic cancer susceptibility.

Women diagnosed with 2 cancers of the breast and/or ovary are at higher risk of developing subsequent cancers. Using registrations from the Thames Cancer Registry, we quantified the risks at different cancer sites. Increased risks were found for cancers that are part of the BRCA1 and BRCA2 tumour spectrum: oropharyngeal cancer, malignant melanoma of the skin (BRCA2) and colon cancer (BRCA1). We also found significantly increased risks of myeloid leukaemia (probably due to radiotherapy) and of cancer of the corpus uteri (which may be due to hormonal factors).

Breast Neoplasms↗

Metastasis of cancer to cancer: report of a case of esophageal carcinoma metastasizing to early gastric cancer.

A rare case of esophageal carcinoma metastasizing to early gastric cancer is reported herein. A 66 year old man who had experienced dysphagia for 8 months was preoperatively diagnosed as simultaneously having esophageal and gastric cancers. Thus, a lower esophagectomy and total gastrectomy with paraesophageal and paragastric lymph node dissection were performed. The surgical specimen revealed an ulcerative tumor in the lower esophagus and a slightly depressed lesion with a central elevation similar to that of early type IIc + IIa gastric cancer in the upper part of the stomach. Microscopically, the esophageal tumor was revealed to be well differentiated squamous cell carcinoma while the gastric tumor was found to be early gastric cancer with a metastatic focus of esophageal cancer in the center. Though less than one hundred cases of metastasis of cancer to cancer have previously been reported, metastasis from cancer of one digestive organ to that of another digestive organ is very rare. To our knowledge, this report represents the first case of an esophageal carcinoma metastasizing to a gastric carcinoma.

Adenocarcinoma↗

Some aspects on validity of breast cancer, pancreatic cancer and lung cancer registration in Swedish official statistics.

From the Regional Cancer Register of Stockholm County and the Swedish Cause-of-Death Register, a total of 1445 individuals were selected. The patients had died in 1978 and were recorded with cancer of breast, pancreas or lung in either (or both) register. Inter-register discordance in regard to diagnostic information was found in 411 cases. Clinical records were retrospectively studied in order to establish the correct diagnosis. In breast cancer, most of the discordance was explained by the numerous deaths from intercurrent causes, though some underestimation of breast cancer as cause of death was noted (5%). Several incorrect entries of pancreas and lung cancer were found in the Cause-of-Death Register, due to inclusion of metastatic disease as primary tumour or non-alteration of the death certificate when a subsequent autopsy showed another diagnosis. In the Cancer Register, few diagnoses of pancreas and lung cancer were found to be incorrect. On the other hand, the register showed a slight undernotification of these tumour types. Routine alteration of death certificates when autopsy gives results differing from the clinical diagnosis and information to doctors concerning the aims, routines and coding procedures at the Cancer and Cause-of-Death Registries, presumably would enhance the accuracy of the registers' statistics.

Breast Neoplasms↗

Frequency of extra-colonic tumors in hereditary nonpolyposis colorectal cancer (HNPCC) and familial colorectal cancer (FCC) Brazilian families: An analysis by a Brazilian Hereditary Colorectal Cancer Institutional Registry.

UNLABELLED: The two main forms of hereditary colorectal cancer are familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). Some families do not meet all the diagnostic criteria for HNPCC or FAP and are classified as familial colorectal cancer (FCC). Little information is available on the spectrum of tumors related to HNPCC and FCC in South America. OBJECTIVE: To describe the frequency of malignant tumors in a group of Brazilian families with HNPCC or FCC in an Institutional Hereditary Colorectal Cancer Registry. MATERIAL AND METHODS: The study included 61 families (29 HNPCC and 32 FCC) between January 1998 and June 2001. HNPCC families were clinically classified according to the Amsterdam Criteria I or II. FCC families were characterized by the presence of at least two individuals with CRC or extra-colonic tumors associated with the HNPCC spectrum, at least one of them being under 50 years of age. RESULTS: In the 29 families with HNPCC, 201 patients with cancer were identified among 1241 individuals (589 men and 652 women). Among the 201 patients 223 tumors were observed: 137 CRC (55 in men and 82 in women) and 86 extra-colonic (37 in men and 49 in women). In the 32 families with FCC, 146 patients with cancer were identified among 1053 individuals (505 men and 548 women); 158 tumors were observed in 146 patients, 75 CRC (33 in men and 42 in women) and 83 extra-colonic tumors (47 in men and 36 in women). The most frequent extra-colonic primary sites among the HNPCC families were: endometrium (26.5%) and breast (26.5%) (women), and stomach (35.1%) (men). Among the FCC families, the most common primary sites were: breast (27.8%) (women), and stomach (44.4%) (men). CONCLUSION: The high frequency of endometrial and gastric cancer found was expected, since these tumors are part of the HNPCC spectrum, but the high frequency of breast cancer requires further molecular investigation to determine a possible hereditary predisposition associated with hereditary CRC.

Adenomatous Polyposis Coli↗

Lumpectomy and breast radiotherapy in breast cancer patients with a family history of breast cancer, ovarian cancer, or both.

This article presents an outcomes review of breast cancer patients identified from the cancer registries of four area hospitals. These patients had family histories of breast cancer, ovarian carcinoma, or both and were treated with conservative surgery and radiation to the involved breast. Patients were as follows: group 1, one first-degree relative ( n = 165, one synchronous bilateral breast cancer); group 2, > or =2 first-degree relatives ( n = 21); group 3, one second-degree relative ( n = 20); and group 4, > or =2 second-degree relatives ( n = 18). The total of patients and breast cancer events was 224 and 225, respectively. Group 5 was a subgroup of 53 patients with a substantial risk (>10%) of a BRCA1 or BRCA2 mutation. After a median follow-up of 3.9 years, 5 patients had local failure (2%), and 5 developed a contralateral breast cancer (2%). There were no significant differences in local failure rates between groups (p = 1.0): group 1, 5 of 166 (3%); group 2, 0 of 21 (0%); group 3, 0 of 20 (0%); and group 4, 0 of 18 (0%). Local failure for group 5 was 2% (1 of 53). Four of 143 patients (3%) with a minimum 3 years of follow-up (median, 5.6 years) had local failure, and 5 (4%) developed a contralateral breast cancer. A univariate analysis was statistically significant for differentiation only (well, 0 of 67; moderately, 1 of 57 [1.8%]; poor, 3 of 26 [11.5%], p = 0.008). Overall survival for groups 1-4 did not differ significantly. Although follow-up has been relatively short, we have not found that breast cancer patients with various degrees of family histories of breast/ovarian carcinoma have had a detrimental outcome when treated with conservative therapy.

Analysis of Variance↗