Lifestyle and cancer: protection from a cancer‐free spouse

Most epidemiological studies on cancer focus on the increase in risk due to a specific exposure. However, with potentially beneficial exposures, such as certain dietary components, it has been practicable to reverse the comparison and assess the decrease in the incidence of cancer when a putative protective factor is present (World Cancer Research Fund, 1997). Concordant cancers in spouses may signal the effects of shared environmental risk factors. Conversely, cohabitation with a cancer-free spouse should provide protection from such risk factors and allow an epidemiological estimate on the magnitude of the effect. Comparison of cancer incidences among spouses has been an underutilized design in the search for cancer causation, although the spouses have often shared their life experiences for decades before the diagnosis of cancer at an old age. The main previous applications of the spouse design have been in the study of passive smoking and anogenital infections. Limited data are available on other possible infective agents, diet, or lifestyles. Here we use the 1999 update of the nationwide Swedish Family-Cancer Database, covering 9.6 million individuals and 0.7 million invasive cancers, to compare site-specific cancer risks among spouses when the index spouse was free from the concordant cancer (Hemminki et al., 1999, 1998). The Database includes offspring born after 1934 with their biological parents, linked to the nationwide Swedish Cancer Registry from years 1958 to 1996. The spouses were identified as the parents of the last child of the couple. The following ICD-7 codes were pooled: “upper aerodigestive” cancer (larynx, lip, mouth, and pharynx), “genital organs” (cervix, vagina, vulva, and penis), “lymphoma” (non-Hodgkin lymphoma, Hodgkin’s disease, and reticulosis), and “leukemia” (leukemias, polycytemia vera, and myelofibrosis). Rectal cancer was separated to anus and mucosal rectum. Basal cell carcinoma of the skin is not registered in the Cancer Registry. Cancer sites were included in the study if more than 2 husband-wife pairs presented with the same, concordant cancer and if diagnosed at ages over 39 years, in order to ensure a minimum time for cohabitation. Person-years of risk were accumulated for each subject from the age of 40 until the date of death, emigration, diagnosis of the cancer, or closing date of 31 December 1996, whichever came first. Directly standardized incidence rate ratios (RR) were calculated as the ratio of age-specific rates for the husbands whose wives did not present with the particular cancer divided by the rates for the husbands whose wives had that cancer (Esteve et al., 1994). Similarly, RRs were calculated for wives by their husbands. Confidence intervals (95% CI) were calculated assuming a Poisson distribution (Esteve et al., 1994). Cancer risk in husbands was analyzed for those whose wives did not present with a concordant cancer in Table I. A similar analysis was done for wives by their husbands. The RR for all sites was 0.99 for both husbands and wives. The uniformity of the site-specific RRs was striking. With a few exceptions, all the RRs were between 0.8 and 1.2, implying that the decades long cohabitation explained little about causation of cancer. The RRs even agreed numerically between husbands and their wives, but this was due to the equal number of pairs used in the ominators. The highest protection was provided against cancer at genital organs, 0.56 for husbands and 0.54 for wives. Protection from genital infections by tumorigenic strains of human papilloma virus is the probable overwhelming cause (zur Hausen, 1999). Spouses were also protected against lung cancer, RR 0.65 and 0.74 for husbands and wives, respectively. This is explained by smoking, which is also the likely contributing reason for the below-unity RRs of upper aerodigestive tract, pancreatic, and urinary bladder cancers, however, none of these were significant. The RRs for stomach cancer were 0.78 and 0.81 for husbands and wives, respectively. Up to 60% of gastric cancers have been attributed to Helicobacter pylori in developed countries, and the infections run in families, however, with some uncertainty about the susceptibility of the adults to infection (Pisani et al., 1997). Protection from Helicobacter is thus the most likely cause for the decreased gastric cancer risk, but modulation by dietary factors cannot be excluded and is even likely. For breast cancer, the RRs were 0.73 and 0.76 for husbands and wives, respectively. The decrease was not statistically significant but raises questions about some contribution of lifestyle factors in male and female breast cancer. The most surprising and provocative finding was the lack of protection at many putative diet-related sites, such as colon, rectum, and kidney. Moreover, there was no evidence that contagious diseases would influence cancer at sites other than those discussed above. Yours sincerely, Kari HEMMINKI* and CHUANHUI DONG Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden