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Background. There is a paucity of knowledge pertaining to the attitudes, feelings, and emotions of women who are at increased familial risk for breast cancer and how these concerns will affect their surveillance behavior. k review of the literature shows an unevenness in the conclusions about these matters, with some reports indicating that anxiety aroused in the familial cancer setting may abet surveillance behavior, whereas other data indicates a negative effect. Methods. The authors reported anecdotal accounts of such behavior in women from hereditary breast and hereditary breast-ovarian cancer prone families. Results. Although these responses of fear, anxiety, and apprehension about cancer risk are not unique to this hereditary cohort, they nevertheless must have been tempered by often life-long exposure of cancer occurrences that may have decimated their families. Conclusions. All accounts agree with the need to devote more research to the special needs--psychological, social, insurance, and general public health measures of these high risk women. Cancer 1994; 74:1184-92. Key words: genetics, psychological, fear, anxiety, high risk, surveillance.

Background. The hereditary flat adenoma syndrome (HFAS) is characterized by an autosomal dominantly inherited predisposition to multiple colonic adenomas (usually less than 100) with proximal predominance and flat as opposed to polypoid growth. Patients with the syndrome experience colorectal cancers in excess, and the lesions are distributed randomly in the colon. The polyps occur at a later age (median, 55 years) compared with age at onset of polyps in patients with familial adenomatous polyposis (FAP) and patients with the Lynch syndromes. FAP and HFAS are linked to the same locus on chromosome 5q21-q22. Methods. Upper endoscopic examination was performed on 22 relatives from four families with HFAS. Results. Fifteen patients from three of these families had multiple fundic gland polyps; four had duodenal or gastric adenomas. Periampullary carcinoma was present in two members from separate families. Conclusions. The authors conclude that the upper gastrointestinal tract pathologic characteristics of HFAS are similar to those described in FAP. Thus, those at risk for HFAS require upper endoscopic screening in addition to meticulous attention to the colon. Cancer 1993; 71:2709-14.

Background. It has been hypothesized that in some but not all families with hereditary nonpolyposis colorectal cancer (HNPCC) there is a high risk of certain cancers other than colon cancer. Methods. The authors compared the observed frequency of cancer at specific sites in more than 1300 high-risk members of 23 kindreds with HNPCC with expectations based on general population incidence and evaluated the hypothesis that there was heterogeneity in cancer frequency among families. Results. The authors observed significantly increased numbers of cancers of the stomach, small intestine, upper urologic tract (renal pelvis and ureter), and ovary. No excess was seen in other cancer types that have been associated previously with HNPCC, including cancer of the breast, pancreas, and urinary bladder. Significant heterogeneity among families was observed in the frequencies of endometrial, ovarian, and upper urologic system cancer. Conclusion. In addition to early onset cancers of the colorectum, HNPCC family members are at increased risk for cancers of other gastrointestinal tract organs, and, especially in some families, cancers of the upper urologic and female genital tract. Concer 1993; 71:677-85.

Background. Hereditary ovarian cancer (HOC) is heterogeneous, with at least three distinctive syndromes, namely, hereditary site-specific ovarian cancer, hereditary breast-ovarian cancer (HBOC) syndrome, and Lynch syndrome II. Ovarian cancer, in accord with virtually all varieties of adult onset cancer, displays an increasing incidence with advancing age; however, it shows an earlier age of onset in hereditary settings. Methods. Detailed medical and pathology studies were performed on extended ovarian cancer-prone pedigrees, with special attention given to age at ovarian cancer onset. Results. The age of onset of ovarian cancer is heterogeneous, wherein the average age of onset in HBOC is 52 years, in hereditary site-specific ovarian cancer it is 49 years, and in the Lynch syndrome II it is 45 years, in contrast to its occurrence in the general population, at an average age of 59 years. Conclusions. These differences are important for the initiation of surveillance and management strategies. Age of onset of ovarian cancer differences in these several hereditary subsets are less striking than they are in the case of other integral forms of cancer in the respective syndromes, such as the breast in the HBOC syndrome. In addition, the phenomenon of extremely early age of onset of ovarian cancer occurs infrequently in HOC when compared to other forms of cancer, such as the breast in HBOC or the colon in Lynch syndrome II. Knowledge about age of onset heterogeneity in HOC may harbor important clues about etiology, pathogenesis, and cancer control. Cancer 1993; 71:573-81.

The terms 'hereditary,' 'sporadic,' and 'familial' colorectal cancer (CRC) suggest a knowledge of causation; however, current understanding of CRC does not permit categorization of differing CRC risks in accord with their cause per se. Despite these serious shortcomings, these terms are defined operationally on the basis of a family history of cancer, and when available, additional phenotypic information. The sporadic type occurs in the absence of a family history of CRC in a first-degree relative. The familial type occurs when at least one first-degree relative has CRC. Both these categories require the exclusion of hereditary CRC. In the case of hereditary CRC, this type is defined as a family history of CRC occurring in a pattern that indicates autosomal-dominant inheritance, which also may involve certain phenotypic signs (depending on the specific disorder, i.e., florid adenomatous polyps, benign and malignant extracolonic lesions, cancer of unusually early onset, and multiple primary cancer, particularly synchronous and metachronous CRC). Although this operational classification does not produce etiologically homogeneous groups, it is believed to have pragmatic utility with respect to planning targeted surveillance and management strategies. Because of the distinctive natural history of CRC in hereditary syndromes, it is of paramount clinical importance to identify hereditary CRC when it does occur. Even in patients with no evidence of hereditary CRC syndrome, their family history may be second only to age in determining the best CRC screening program for those who are asymptomatic. In an attempt to provide a perspective on the clinical evaluation of CRC risk, research was reviewed on pathologic features and biomarkers that may be related to CRC causes, especially the genetic basis of CRC susceptibility. The long-term objective of studies on the genetic epidemiology of CRC is primary and secondary prevention through development of targeted management and surveillance recommendations (based on an understanding of CRC causation) that is relevant to hereditary, familial, and sporadic CRC. Cancer 1992; 70:1300-1312.

Hereditary breast cancer (HBC) is noteworthy for certain unique facets of its natural history and heterogeneity. Interfamily heterogeneity in age at initial breast cancer diagnosis was investigated in 217 family members with HBC. The mean age at diagnosis was 44.9 years (standard deviation [+ or -] 12.5 years). A one-way analysis of variance in ages at diagnosis, using the family as a random effect factor, indicated that between-family differences were significant (P < 0.002) and accounted for approximately 18% of the variance in ages at diagnosis. A subset of families with HBC was characterized by an extraordinarily early onset of breast cancer. A knowledge of the natural history of HBC with particular attention to age at onset allows for the development of more accurately targeted surveillance, genetic counselling, and management strategies. (Cancer 1992; 69:1404-1407.

Little is known about the contribution of genetic factors to the development of ovarian cancer. While the majority of ovarian cancer cases occur sporadically, the disease may also occur within families. There is some indication that ovarian cancer may be transmitted as an autosomal dominant trait in these families. However, not all families in which ovarian cancer occurs are comparable. In some families, the hereditary cancer is specific for the ovary. However, other families may carry the breast-ovarian cancer syndrome. Still other families carry Lynch syndrome II, in which ovarian cancer is associated with hereditary nonpolyposis colorectal cancer. The authors have compared the features of ovarian cancer in a collection families representing each of these three familial ovarian cancer syndromes. Pathological examination did not reveal any characteristics that distinguished the hereditary cancers from the sporadic neoplasms. However, a difference in the age of onset was observed. The average (mean) age of onset for ovarian cancer in the general population is 59 years; the median age is 60 years. For 52 patients with hereditary breast-ovarian cancer in this study, the mean age at diagnosis was 52 years. For the 15 cases of Lynch syndrome II, which were included in the statistical analysis, the mean age at diagnosis was 45 years. A mean age at diagnosis of 49 years was observed for the patients with site-specific familial ovarian cancer. While the age at diagnosis for the three familial cancer syndromes was significantly less than for the population as a whole, the differences among the three syndromes were only marginally significant. Nevertheless, these differences suggest that various mechanisms may be responsible for the development of ovarian cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

Most physicians are aware of familial polyposis syndrome, or familial adenomatous polyposis, as a genetic risk factor for colorectal cancer. However, many mistakenly believe that it is the only genetic predisposition to colon cancer. In reality, familial polyposis accounts for only about one percent of colorectal cancer, while hereditary nonpolyposis syndromes may be from six to eight times more common. Two major nonpolyposis syndromes, which the authors refer to as Lynch syndromes I and II, may be recognized by careful evaluation of the family history, but the authors feel that inadequate attention is given to this by the majority of physicians. They illustrate this point by recounting the diagnosis of Lynch syndrome II in an extended kindred in a midwestern community. Lynch syndrome II involves not only cancer of the colon and rectum, but also of the endometrium and ovaries as well. Despite the regular occurrence of these tumors over five generations, the syndrome was not recognized in this kindred due to scant attention paid to the family history. Lynch syndrome II is also distinguished by the early onset of the cancer and the proximal predominance of adenocarcinoma of the colon. The syndrome is inherited as an autosomal dominant trait. The authors point out that no known cancer risk factor is greater than the roughly 50 percent risk carried by a first-degree relative of a patient with autosomally dominant inherited colorectal cancer. Nevertheless, within the current preoccupation with dietary factors, many physicians continue to give short shrift to the family history in cases of colorectal cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

Familiar adenomatous polyposis (FAP) was the first colorectal cancer found to be inherited. The disorder accounts for about one percent of all colorectal cancer. More recently hereditary nonpolyposis colorectal cancer (HNPCC) has been found to involve a dominantly inherited predisposition to the early development of colorectal cancer. This form of familial colorectal cancer is far more common than familial adenomatous polyposis, and may account for more than six percent of all colorectal cancers. Familial adenomatous polyposis has been found to be linked to the long arm of chromosome 5, but the genetic linkage of hereditary nonpolyposis colorectal cancer has not yet been identified. Now, however, two families have been identified in which an inherited syndrome of adenomas and colorectal cancer does not fall into either of these classifications. The average age of cancer onset within these two families is 57 years, in contrast to 40 years for familial adenomatous polyposis and 45 years for hereditary nonpolyposis colorectal cancer. The histologic appearance of the adenomas is flat, in contrast to the tubular adenomas seen in the previously identified syndromes. (Flat refers to essentially horizontal rather than vertical growth of the tumor.) The polyp and cancer distribution is largely on the right side, which resembles HNPCC, but the number of observed polyps is generally between HNPCC and (that is, more than 10, but less than 100 polyps, respectively). The cancer syndrome in these two families appears to be transmitted as an autosomal dominant trait (not sex-linked), and the authors suggest that it may represent an intermediate cancer, between HNPCC and FAP. Preliminary genetic linkage studies are consistent with a linkage of this newly identified colorectal cancer syndrome to the FAP locus on chromosome 5. However, the lod score of 2.7 may be regarded only as suggestive, and not conclusive of this genetic linkage. (Lod refers to the log of the odds ratio; a score of four or greater is generally accepted as indicative of genetic linkage.) (Consumer Summary produced by Reliance Medical Information, Inc.)

Background. Sulindac is reported to induce regression of colonic adenomas. However, its role as a chemoprophylactic agent for people with familial adenomatous polyposis (FAP) is under consideration. Methods. This case report describes a patient with FAP in whom rectal adenocarcinoma developed 37 years after prophylactic colectomy and 15 months after beginning a course of sulindac. She received endoscopic follow-ups every 3 months during 15 months of 150-mg twice-daily sulindac administration. At 12 months, an endoscopic examination was unremarkable; at 15 months, endoscopic examination revealed several polyps and a flat ulcerated lesion. Results. Rectal carcinoma developed in a patient 15 months after beginning chemoprophylaxis; there was metastatic adenocarcinoma in 6 of 20 perirectal lymph nodes. In addition to the carcinoma, rectal mucosa contained two adenomas and multiple foci of adenomatous changes in flat mucosa. Conclusion. Sulindac may not alter the pathogenesis of FAP. Patients undergoing sulindac chemoprevention must be monitored closely, including endoscopic examination. Endoscopic surveillance should include an aggressive biopsy approach because the absence of polyps does not prove the absence of neoplastic change. Cancer 1995;75:936-8.