• family history;
  • cancer susceptibility;
  • sibling history;
  • smoking



Inherited genetic predispositions are important risk factors for the development of cancer in general. To determine genetic susceptibility for 14 common cancers, a case–control study of the impact of a family history of cancer in first-degree relatives was conducted. The authors further evaluated the effect modification by habitual smoking with adjustment for other confounding environmental factors.


In total, 18,836 cancer cases and 28,125 age–matched and sex–matched controls, confirmed as being free of cancer, were recruited. Odds ratios (ORs) and 95% confidence intervals were determined by multiple logistic regression analysis, including stratification by family history for 14 cancer sites and interactions with a smoking history.


The associations between family history and risk of cancer were generally stronger at the same sites than across cancer sites. Risks to first-degree relatives at the same sites were found to be significantly elevated with 8 of 14 cancer sites; especially high ORs were found for prostate and thyroid cancers. Some across-site associations were observed; in particular, a reciprocal association between breast and prostate cancer was found. The interaction between family history and smoking history for breast cancer was found to be statistically significant. There was no statistical evidence for the interactions in other sites, but among subjects with a family history, the ORs were found to be higher in smokers compared with nonsmokers.


The results of the current study support the hypothesis of a genetic susceptibility to cancers in family members. For breast cancer, the interaction between family history and smoking history was observed to be significant. Cancer 2007. © 2007 American Cancer Society.