Frederick F. Holmes

Early menopause in long-term survivors of cancer during adolescence

Objective: We attempted to investigate the risk of early menopause after treatment for cancer during childhood or adolescence. Study Design: We interviewed 1067 women in whom cancer was diagnosed before age 20, who were at least 5-year survivors, and who were still menstruating at age 21. Self-reported menopause status in survivors was compared with that in 1599 control women. Results: Cancer survivors, with disease diagnosed between ages 13 and 19, had a risk of menopause four times greater than that of controls during the ages 21 to 25; the risk relative to controls declined thereafter. Significantly increased relative risks of menopause during the early 20s occurred after treatment with either radiotherapy alone (relative risk 3.7) or alkylating agents alone (relative risk 9.2). During ages 21 to 25 the risk of menopause increased 27-fold for women treated with both radiation below the diaphragm and alkylating agent chemotherapy. By age 31, 42% of these women had reached menopause compared with 5% for controls. Conclusions: Treatment for cancer during adolescence carries a substantial risk for early menopause among women still menstruating at age 21. Increasing use of radiation and chemotherapy, together with the continued trend toward delayed childbearing, suggests that these women should be made aware of their smaller window of fertility so that they can plan their families accordingly.

Genetic Disease in Offspring of Long-Term Survivors of Childhood and Adolescent Cancer

Numerous case series have addressed the concern that cancer therapy may damage germ cells, leading to clinical disease in offspring of survivors. None has documented an increased risk. However, the methodological problems of small series make it difficult to draw firm conclusions regarding the potential of cancer treatments to damage the health of future offspring. We conducted a large interview study of adult survivors of childhood cancer treated before 1976. Genetic disease occurred in 3.4% of 2,198 offspring of survivors, compared with 3.1% of 4,544 offspring of controls (P=.33; not significant); there were no statistically significant differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with survivors not so treated showed no association with sporadic genetic disease (P=.49). The present study provides reassurance that cancer treatment using older protocols does not carry a large risk for genetic disease in offspring conceived many years after treatment. With 80% power to detect an increase as small as 40% in the rate of genetic disease in offspring, this study did not do so. However, we cannot rule out the possibility that new therapeutic agents or specific combinations of agents at high doses may damage germ cells.

Metastatic cancer of unknown primary site

Characteristics of 686 patients with the diagnosis of metastatic cancer of unknown primary site are examined. Average age of the series is 60.2 years and ratio of males to females is 58:42. Bones, lungs, and liver are the common sites of metastases, and adenocarcinoma, carcinoma, and anaplastic carcinoma are the most common histologic types. Survival for all patients is: 2‐year 10.4%, 5‐year 5.1%, and 10‐year 3.3%. Average age of the 27 patients surviving 5 years or longer is 52.5 years of the 14 patients of this latter group now dead, only 2 died of cancer. Speculation about both elusive primary tumors and occasional long survival must include primary tumors too small to be found at either clinical examination or autopsy, inadvertent removal or destruction of primary earlier by physician or sloughing by host, or destruction or containment of tumor by host defense mechanisms.

Pregnancy outcome of patients treated for Hodgkin's disease. A controlled study

Normal reproduction prospects for Hodgkins disease patients are unknown. This study compares the outcome of 93 pregnancies in 48 patients with 228 pregnancies in 69 sibling controls. No statistically significant differences for spontaneous abortions or abnormal offspring were noted comparing all patients with all controls or 35 irradiated patients with all controls. Pregnancy outcome of 13 patients who received both irradiation and chemotherapy prior to pregnancy appeared to be compromised compared to controls. Wives of male patients in this category were more likely to have spontaneous abortions than wives of male controls; female patients in this category were significantly more likely to produce abnormal offspring than were female controls (p = 0.047). In this series of patients therapeutic irradiation alone did not appear to jeopardize posttreatment reproduction in fertile Hodgkins disease patients but in the smaller group of patients who received both irradiation and chemotherapy the reproduction picture was statistically not as good.

CANCER IN OFFSPRING OF LONG-TERM SURVIVORS OF CHILDHOOD AND ADOLESCENT CANCER

A multicentre retrospective cohort study of long-term survivors of childhood and adolescent cancer identified 7 cases of cancer among 2308 offspring (0.30%) of 2283 case-survivors and 11 cases among 4719 offspring (0.23%) of 3604 controls. Overall, the observed numbers of cases were not significantly different from those expected in the general population. Among offspring of case-survivors observed for the first 5 years of life, the group with the most person-years of follow-up, 5 cancers were reported (3 confirmed), compared with 1.7 expected, a significant excess due mostly to boys whose mothers survived cancer. Some offspring with cancer had known single-gene traits; others resembled previously recognised patterns of family cancer. The remainder may represent chance occurrences or new cancer family syndromes, such as an association with malignant melanoma. The study had an overall 79% power to detect a 3-fold excess of cancer among offspring of case-survivors, but no excess was observed. The number person-years of follow-up in the second decade of life, when most cases of cancer developed, was small.

Agricultural use of organophosphate pesticides and the risk of non-Hodgkin's lymphoma among male farmers (United States)

AbstractObjective: Data from three population-based case–control studies conducted in Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate the relationship between the use of organophosphate pesticides and non-Hodgkins lymphoma (NHL) among white male farmers. Methods: The data set included 748 cases of non-Hodgkins lymphoma and 2236 population-based controls. Telephone or in-person interviews were utilized to obtain information on the use of pesticides. Odds ratios (OR) adjusted for age, state of residence, and respondent status, as well as other pesticide use where appropriate, were estimated by logistic regression. Results: Use of organophosphate pesticides was associated with a statistically significant 50% increased risk of NHL, but direct interviews showed a significantly lower risk (OR = 1.2) than proxy interviews (OR = 3.0). Among direct interviews the risk of small lymphocytic lymphoma increased with diazinon use (OR = 2.8), after adjustment for other pesticide exposures. Conclusions: Although we found associations between the risk of NHL and several groupings and specific organophosphate pesticides, larger risks from proxy respondents complicate interpretation. Associations, however, between reported use of diazinon and NHL, particularly diffuse and small lymphocytic lymphoma, among subjects providing direct interviews are not easily discounted.

Anal cancer in women.

We studied predisposing factors in 56 women with anal cancer, comparing them with 56 matched controls drawn from the population. A detailed pretested questionnaire was administered to each study subject in a structured interview and blood was drawn for detection of herpes simplex virus antibodies by radioimmunoassay. Pathologic material from cases was obtained and evidence of human papilloma virus infection was sought. By univariate analyses we found associations between anal cancer and positive herpes simplex virus 2 titer (p = 0.0017), cigarette smoking (p = 0.0028), previous positive or questionable cervical Papanicolaou smear (p = 0.0124), and increasing number of sexual partners (p = 0.0224). By the multivariate technique of logistic regression there were independent and significant associations with cigarette smoking (p = 0.0126), previous use of hemorrhoid preparations (p = 0.0149), and history of disturbed bowel habits for greater than 1 mo (p = 0.0273). Anal cancer in women is a rare disease associated with cigarette smoking and sexual experience. Its association with previous anorectal disease is unclear and deserving of further study.

Lung carcinoma in the elderly population. Influence of histology on the inverse relationship of stage to age.

Unlike most cancers, lung carcinoma is more likely to be localized at the time of diagnosis in older age groups when compared to those who are middle‐aged. In an attempt to explain this inverse age–stage relationship we studied 9062 histologically confirmed cases of lung carcinoma occurring from 1975 to 1984 obtained from the regional cancer registry for Kansas and western Missouri. They were analyzed according to histologic type, age, sex, and stage at diagnosis. The data suggest that the proportion of squamous cell carcinoma rises and that of adenocarcinoma and small cell undifferentiated carcinoma falls with increasing age. The proportion of staged lung carcinoma with local disease at the time of diagnosis increases with age. In males this trend occurred in all cell types except large cell undifferentiated carcinoma but was most significant for squamous cell carcinoma. Squamous cell carcinoma was the only group to show a significant trend among females. The rise in squamous cell and fall in small cell carcinoma may partially explain the increased prevalence of local stage disease with advancing age.

Tobacco and non-Hodgkin's lymphoma: combined analysis of three case-control studies (United States)

The role of tobacco in the etiology of non-Hodgkins lymphoma (NHL)was evaluated in a combined analysis of data from three population-basedcase-control studies conducted in four midwestern states of the UnitedStates: Nebraska, Iowa, Minnesota, and Kansas. Interviews were obtained from1,177 cases (993 men, 184 women) and 3,625 controls (2,918 men, 707 women )or, if deceased, from their next-of-kin. Overall, there was no associationbetween NHL and tobacco use (odds ratio [OR] = 1.0, 95 percent confidenceinterval [CI] = 0.8-1.1) or cigarette smoking (OR = 1.0, CI = 0.8-1.1). Aslight negative association evident in analyses by intensity and duration ofsmoking was not present when interviews from proxy respondents wereeliminated. There was a suggestion of a positive association between smokingand NHL among women (OR = 1.3, CI = 0.9-1.9), although there was no clearexposure-response relationship. This large case-control analysis provides noevidence that smoking is linked to the development of NHL among men. Thepossible role of smoking in the etiology of NHL among women needs furtherevaluation.

Female gender is a major determinant of changing subsite distribution of colorectal cancer with age

Distribution by subsite and sector of 948 colorectal cancers diagnosed in Kansas in 1982 was analyzed in respect to sex and age in a population‐based study. Regression analysis of percentage versus age showed decreasing left, increasing right, and unchanged transverse colon occurrence of cancer for both sexes. However, this was statistically significant only for women; left, −0.7066% per year (P = 0.0088) and right +0.6023% per year (P = 0.0012). Regression for seven subsites showed significant changes only for women; with rectosigmoid and sigmoid decreasing and cecum and ascending colon increasing. Similar results were obtained in analysis of the 5822 cases available in the Kansas cancer registry for the years 1978 to 1982. These findings have important implications for screening and diagnosis of colorectal cancer in the elderly, particularly women, and also provide a useful clue in the investigation of colorectal carcinogenesis.