Sex of first child and breast cancer survival in young women.

Two studies have reported that young women with breast cancer face increased risk of early mortality if their first child was male rather than female. An immunological mechanism has been suggested. We sought to confirm these results in a larger, historical cohort study of 223 parous women who were aged <45 years at breast cancer diagnosis during 1983-1987. Subjects were identified through the Maine Cancer Registry. Follow-up data were obtained from hospitals, physicians, and death certificates. Reproductive history data were obtained from the next of kin of the deceased women, birth certificates, physicians, hospitals, and lastly, subjects. With a 7-year follow-up, multivariate modeling found a lower mortality risk in women with a male first child (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.32-0.81, log-rank comparison). The survival advantage remained for at least 13 years in women with a male firstborn. Thus, previous studies were not confirmed. Mortality risk in young women with breast cancer is not increased by having borne a male first child rather than a female first child.

The fetal antigen hypothesis: cancers and beyond.

Twenty years ago the fetal antigen hypothesis was proposed as a potential mechanism by which women are naturally immunized against cancer antigens by antigens from their fetus. Evidence from recent clinical studies shows that a high percentage of parous woman, but not nulliparous women, show evidence of immunization to antigens found on breast, ovarian and endometrial cancer cells. I suggest that this maternal immunization also affects the fetus, causing early immune rejection of fertilized ova that express cancer-related genotypes. Additional cancers, and perhaps even other types of genetic diseases, may be involved in this mechanism.

Relation between body mass index and lung cancer risk in men and women never and former smokers.

The authors assessed body mass index (BMI), measured as Quetelet's index (weight in kilograms divided by the square of height in meters), in relation to lung cancer risk in never and former smokers by using data from a population-based, individually matched, case-control study conducted in New York State from 1982 to 1985. To be included in the study, subjects must never have smoked more than 100 cigarettes in their lifetime (never smokers) or not have smoked more than 100 cigarettes during the last 10 years (former smokers). Data on height and weight were complete for 412 of 439 case-control pairs. A positive relation was found between BMI and lung cancer risk for both never smokers (188 case-control pairs) and former smokers (224 pairs). When subjects were combined, those in the eighth (highest) octile (BMI > 30.84) had more than twice the odds of being cases compared with those in the lowest octile (BMI < or =21.26, 95 percent confidence interval: 1.2, 4.4). These study results are consistent with those from studies of BMI and other cancer sites but differ from lung cancer results usually found in predominantly smoking populations.

Familial cancer history and lung cancer risk in United States nonsmoking men and women.

The authors conducted a population-based case-control study of lung cancer in nonsmoking men and women in New York State from 1982 to 1984. Nonsmokers included both never smokers (45%) and former smokers who had quit at least 10 years before diagnosis/interview (55%). In-person interviews were completed for 437 lung cancer cases and 437 matched population controls. Cases and controls were asked to report on their family history of cancer, as well as smoking status of family members. Cases were significantly more likely than controls to report having a paternal history of any cancer [odds ratio (OR), 1.67] and aerodigestive tract cancers (OR, 2.78); a maternal history of breast cancer (OR, 2.00); a history of any cancer in brothers (OR, 1.58) and sisters (OR, 1.66); and a nearly significant excess of lung cancer (OR, 4.14; P = 0.07), aerodigestive tract cancer (OR, 3.50; P = 0.06), and breast cancer (OR, 2.07; P = 0.053) in sisters. The excess risk in relatives of cases as compared to relatives of controls also was evident in a cohort analysis of the relatives. These results support the hypothesis of a genetic susceptibility to various cancers in families with lung cancer in nonsmokers.

Previous lung disease and risk of lung cancer among men and women nonsmokers.

From 1982 to 1984, the authors conducted a population-based case-control study of lung cancer in men and women nonsmokers in New York State. In-person interviews were completed for 437 lung cancer cases (197 never smokers, 240 former smokers) and 437 matched population controls. Cases and controls were asked to report any history of physician-diagnosed nonmalignant lung disease; cases were more likely than controls to report such a history. Statistically significant associations were found for emphysema (odds ratio (OR) = 1.94, 95% confidence interval (CI) 1.10-3.43), chronic bronchitis (OR = 1.73, 95% CI 1.10-2.72), and the combined endpoint of emphysema, chronic bronchitis, or asthma (OR = 1.82, 95% CI 1.26-2.63). After adjustment for active and passive tobacco smoke exposure, emphysema, chronic bronchitis, and asthma (each condition and the combined endpoint) were significantly associated with lung cancer risk. The risk was more marked for squamous cell carcinomas and for subjects who were diagnosed at older ages, and it remained significant when surrogate interviews were excluded. These results are consistent with the hypothesis that certain prior lung conditions increase the risk of lung cancer in men and women nonsmokers.

The fall in incidence of prostate carcinoma. On the down side of a prostate specific antigen induced peak in incidence--data from the Utah Cancer Registry.

BACKGROUND: In the 1980s, prostate specific antigen (PSA) came into wide use as a prostate carcinoma screening and detection method in the United States. Following the introduction of PSA, the age-adjusted incidence of prostate carcinoma reported by the Surveillance, Epidemiology, and End Results (SEER) program in the United States rose rapidly (from 84.4/100,000 in 1984 to 163/100,000 in 1991). When an increase in incidence is observed following the introduction of a screening method, a subsequent decrease in incidence may be expected as prevalent cases are removed from the population (a cull effect). Incidence rates may also fall due to factors such as decreased intensity of screening. The Utah Cancer Registry data were examined for a decrease in prostate cancer incidence. METHODS: We tracked age-adjusted prostate carcinoma incidence trends from the population-based Utah Cancer Registry and compared them with rates from the SEER national registry. RESULTS: A rapid and highly correlated rise in prostate carcinoma incidence has been observed in both SEER and Utah incidence rates between 1988 and 1991, the last year for which SEER data are available. In 1992, Utah incidence rates peaked at 236.2 per 100,000. In 1993 and 1994, Utah incidence rates fell to 195.0, and an estimated 164.0 per 100,000, respectively. CONCLUSIONS: Population-based data from the Utah Cancer Registry indicates that the incidence of prostate carcinoma is decreasing rapidly after a similarly rapid increase.

The screening histories of women with invasive cervical cancer, Connecticut.

OBJECTIVES: Each case of a continuous series of invasive cervical cancer cases was studied with a structured review procedure conducted by an expert panel to assess the reason that it was not detected before it became invasive. METHODS: All cases of invasive cervical cancer diagnosed in a 5-year period among Connecticut residents were identified; a screening history and screening outcome were obtained for 72% (481 of 664). RESULTS: Two hundred fifty women (51.9%) had suboptimal screening. One hundred thirty-seven women (28.5%) had never had a screening test, and their mean age was greater than that of the rest of the study population (64.5 years vs 46.5 years). Of the 344 women who had ever had a Pap test, 113 (32.8%) had their last Pap test 5 or more years before their diagnosis of invasive cancer; 52 (15.1%) were not followed up properly; 33 (9.6%) had their last smear misread as normal; and 118 (34.3%) developed cervical cancer within 3 years of their last Pap test. CONCLUSIONS: Physicians, nurses, and other care providers need to ensure that woman have timely and accurate screening with proper follow-up, make increased efforts to reach older women, and improve quality control of Pap smear readings.

Reduced breast cancer risk after remarriage: evidence of genetic-immune protection.

Several reproductive factors have been found to be associated with breast cancer. Based on an immunologic rather than strictly hormonal interpretation of these observations, we hypothesized that, beyond the observed associations relating to pregnancy per se, multiple marriages would be found to protect women against breast cancer. We obtained cases and controls from linked records from the Utah Cancer Registry and genealogic records. A total of 2,414 women with newly diagnosed breast cancer and 9,138 individually matched controls were included. The unadjusted odds ratio for each marriage after the first was 0.81 [95% confidence interval (CI) = 0.68-0.97]. After adjustment for major reproductive factors, multiple marriages were still found to reduce the risk of breast cancer (odds ratio = 0.86; 95% CI = 0.72-1.03). The findings are consistent with the operation of an immunologic mechanism in the etiology of breast cancer and suggest that the gene/antigen responsible for this effect is quite common in males. Further empirical evaluation of the fetal antigen hypothesis seems warranted.

Maternal pattern of reproduction and risk of breast cancer in daughters: results from the Utah Population Database.

BACKGROUND: Several studies have found that daughters born to older mothers have an elevated risk of breast cancer, and an endocrine hypothesis, among others, has been developed to explain these findings. Three recent studies have failed to find a consistent maternal age effect, indicating a need for further exploration of this issue. PURPOSE: We used Utah breast cancer records linked to genealogical records to investigate maternal and paternal age and other maternal reproductive factors in relationship to the daughter's risk of breast cancer. METHODS: The study group consisted of 2414 breast cancer case patients and 9138 individually matched control subjects. Breast cancer diagnoses were ascertained through the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The case patients and control subjects were born between 1875 and the end of 1947, and the mean age at diagnosis of the case patients was 65.9 years. RESULTS: No consistent effect for maternal or paternal age was found, except possibly among women who were firstborn children (odds ratio [OR] = 1.42 for a 10-year differential in maternal age; 95% confidence interval [CI] = 1.00-2.00). Further examination of the data indicated that mothers of case patients experienced long intervals between marriage and their first birth but not between subsequent births, and they went on to have fewer children. For each year of delay between the mother's marriage and first birth, the odds of breast cancer in the daughter increased 1.05-fold (95% CI = 1.01-1.10). CONCLUSIONS: We found no evidence of a consistent maternal age effect with regard to breast cancer risk in the daughter, but we did find evidence that the mothers of women who go on to get breast cancer have a reproductive pattern that could suggest some form of underlying infertility. IMPLICATIONS: These findings widen the epidemiologic support for the fetal antigen hypothesis, which is an immunogenetic explanation for the relationships between reproductive factors and breast cancer risk. That hypothesis provides strategies for the identification of breast cancer genes and the eventual development of a breast cancer vaccine.

The fetal antigen hypothesis for breast cancer, revisited.

The fetal antigen hypothesis was proposed over a decade ago to explain the small, short-term promotional effect, as well as part of the long-term protective effect that pregnancy has on breast cancer risk. The hypothesis is based on immune interaction between mother and fetus, and postulates that breast cancer genes which a women's fetus inherits from her mate may be indirectly involved in protecting the woman against breast cancer. This article addresses new epidemiological data pertaining to the hypothesis plus the growing evidence that prenatal reproductive factors are important determinants of breast cancer risk. It also suggests that iso-immunization from pregnancy, similar to Rh iso-immunization, can produce immunity against breast cancer. The proposed mechanism provides a plan for development of a vaccine against breast cancer. If the fetal antigen hypothesis is valid for breast cancer, the mechanism behind it is likely to apply to other cancers, even cancers that are found in males, since males can be affected be the prenatal component of this mechanism.

Dietary beta carotene and lung cancer risk in U.S. nonsmokers.

BACKGROUND: Approximately 15% of all lung cancer deaths in the United States (about 22,350 deaths annually) may not be directly attributable to active cigarette smoking. Consumption of beta carotene, which is derived almost exclusively from intake of fruits and vegetables, has been associated with a reduced risk of lung cancer in smokers. However, studies examining this association in nonsmokers, particularly nonsmoking men, are limited. PURPOSE: The purpose of this study was to examine whether dietary factors including beta carotene and retinol are associated with a reduced risk for lung cancer in nonsmoking men and women. METHODS: A population-based, matched case-control study of lung cancer in nonsmokers was conducted in New York State from 1982 to 1985. Dietary interviews were completed for 413 individually matched case-control pairs of subjects. To determine whether the relationship between dietary intake from specific food groups and lung cancer differed by type of interview, smoking history, sex, age, or histologic type, we examined data on the case-control pairs from each subgroup separately. The intake of beta carotene and retinol was calculated as the weighted sum of the monthly frequencies of consumption of food items containing these nutrients, where the weights correspond to the nutrient content of a typical portion of the food items. RESULTS: Consumption of greens (P for trend < .01), fresh fruits (P for trend < .01), and cheese (P for trend < .05) was associated with a significant dose-dependent reduction in risk for lung cancer, whereas consumption of whole milk (P for trend < .01) was associated with a significant dose-dependent increase in risk. Use of vitamin E supplements was also protective (odds ratio = 0.55; 95% confidence interval [CI] = 0.35-0.85). Increased consumption of the following food groups was associated with a reduction in risk among females: vegetables (P for trend < .025), raw fruits and vegetables (P for trend < .005), and dairy products (P for trend < .025). In males, increased consumption of raw fruits and vegetables was associated with a reduced risk for lung cancer (P for trend < .005). Dietary beta carotene (OR = 0.70; 95% CI = 0.50-0.99), but not retinol (OR = 0.98; 95% CI = 0.82-1.17), was significantly associated with risk reduction. CONCLUSIONS: This is the largest study to date of dietary factors and lung cancer in nonsmokers; results suggest that dietary beta carotene, raw fruits and vegetables, and vitamin E supplements reduce the risk of lung cancer in nonsmoking men and women.

Gender of the first offspring, age at diagnosis, and survival with breast cancer (Utah, United States).

We examined the relationship between the survival of women with breast cancer and the gender of their first children using a genealogy-based survival analysis. The study group consisted of 2,155 parous women diagnosed in Utah (United States) with first primary breast cancers (excluding in situ tumors). We calculated hazard rate ratios (HRR) which were adjusted for stage, median survival times, and proportions surviving for three-, five-, and 10-year intervals stratified by age at diagnosis. Median survival among women diagnosed under the age of 45 was 171 months if the first child was female, but only 66 months if the first child was male (HRR = 1.66, 95 percent confidence interval = 1.07-2.57, for male children). For women diagnosed at age 45 or older, all survival times were similar, although women whose first child was male had slightly longer median survival time. These findings suggest that the gender of the first child has a strong influence on survival among women diagnosed under 45 years of age, but not among those diagnosed later in life. Gender of the first offspring may be a useful clinical indicator of prognosis and survival and may provide insights into etiologic and promotional factors for breast cancer.

Cervical cancer rates by population size of towns: implications for cancer control programs.

Incidence rates and standardized incidence ratios (SIRs) for invasive and in situ cervical cancers diagnosed in 1982-87 were analyzed according to total population size of 148 towns, using data from the population-based Connecticut Tumor Registry. Previous studies have not considered socioeconomic or sociodemographic variables in analyzing cervical cancer rates in urban-rural or population density groups. In multiple regression analyses, increases in SIRs for invasive and in situ cancer from medium-sized to large towns were explained by differences in poverty prevalence or other socio-demographic variables. Nevertheless, cancer screening programs (aimed at preventing invasive cancer through early detection) could be targeted to some extent on the basis of town size category, because larger towns include large numbers of poorer and minority women with higher rates of invasive cervical cancer. SIRs for in situ cancer were significantly elevated in the largest towns (100,000 + total population), and primary prevention programs could target these larger towns with a higher prevalence of poverty.

Alcohol and pregnancy. An epidemiologic perspective.

This article considers maternal use of alcohol during pregnancy, from an epidemiologic perspective. In general, maternal use of alcohol during pregnancy has been associated with a number of effects in offspring including fetal alcohol syndrome, a reduction in birth weight, effects on behavior, and other late effects. It is apparent from the existing literature that the epidemiologic dimensions of these effects are poorly defined and hampered by methodologic problems. Assessment of both outcome and exposure can be difficult, and there is great potential for uncontrolled confounding. Additionally, it is unclear whether the apparent teratogenicity of alcohol results from direct, acute effects of alcohol on the developing fetus, or results from chronic effects of excessive alcohol intake in the mother. This article concludes with recommendations for further research, which may help clarify the complexity of effects associated with maternal use of alcohol during pregnancy.

Familial clustering of neural tube defects and gastric cancer.

A retrospective cohort study was conducted to determine whether producing an offspring with a neural tube defect (NTD) is associated with the development of unusual patterns of cancer among the parents in subsequent years. Mothers and fathers who had a child with an NTD in Upstate New York from 1945 to 1955 were followed through 1979 and compared to a control group of parents with normal offspring. Overall mortality and site-specific cancer incidence were not significantly different for case parents versus control parents, with the exception of gastric cancer, which occurred significantly more frequently in case parents. The finding of a familial association between NTDs and gastric cancer, coupled with a parallel decline in rates of these two diseases, suggests a common aetiology, perhaps related to dietary factors.

Lung cancer and exposure to tobacco smoke in the household.

BACKGROUND: The relation between passive smoking and lung cancer is of great public health importance. Some previous studies have suggested that exposure to environmental tobacco smoke in the household can cause lung cancer, but others have found no effect. Smoking by the spouse has been the most commonly used measure of this exposure. METHODS: In order to determine whether lung cancer is associated with exposure to tobacco smoke within the household, we conducted a population-based case--control study of 191 patients with histologically confirmed primary lung cancer who had never smoked and an equal number of persons without lung cancer who had never smoked. Lifetime residential histories including information on exposure to environmental tobacco smoke were compiled and analyzed. Exposure was measured in terms of "smoker-years," determined by multiplying the number of years in each residence by the number of smokers in the household. RESULTS: Household exposure to 25 or more smoker-years during childhood and adolescence doubled the risk of lung cancer (odds ratio, 2.07; 95 percent confidence interval, 1.16 to 3.68). Approximately 15 percent of the control subjects who had never smoked reported this level of exposure. Household exposure of less than 25 smoker-years during childhood and adolescence did not increase the risk of lung cancer. Exposure to a spouse's smoking, which constituted less than one third of total household exposure on average, was not associated with an increase in risk. CONCLUSIONS: The possibility of recall bias and other methodologic problems may influence the results of case-control studies of environmental tobacco smoke. Nonetheless, our findings regarding exposure during early life suggest that approximately 17 percent of lung cancers among nonsmokers can be attributed to high levels of exposure to cigarette smoke during childhood and adolescence.

Maternal age at birth and risk of breast cancer in daughters.

Data from a large case-control study of breast cancer were examined to test the hypothesis that maternal age at the birth of female offspring is related to the incidence of breast cancer in daughters. Participants were between the ages of 20 and 54 at the time of the study. Based on results for 2,492 parous women who were newly diagnosed with breast cancer and 2,687 parous controls from the general population, a 15-year increase in maternal age was found to be associated with a 29% increase in the risk of breast cancer in daughters. Adjustment for the daughter's age, her own reproductive history, and other potential confounding factors yielded an estimate of 25% for this increase in risk (95% CI, 8% to 46%). The corresponding increase among 499 nulliparous cases and 457 nulliparous controls was 7%, which was not statistically significantly different in magnitude from the increase among parous women. These findings provide evidence for perinatal influences on the subsequent incidence of breast cancer during adulthood. Although specific mechanisms cannot be inferred directly, the results are consistent with the hypothesis that mutations in the genes of the human egg or sperm play a role in the etiology of breast cancer in female offspring.