Family history of hormonal cancers and colorectal cancer risk: A case‐control study conducted in Ontario

Abstract

Aggregation of cancers among families with highly penetrant genetic mutations such as hereditary nonpolyposis colorectal cancer is well-described. However, there is a paucity of data regarding familial aggregation of hormonal cancers (cancers of the breast, endometrial, ovarian and prostate) and colorectal cancer (CRC) in the general population. We investigated the association between having a first-degree family history of breast, endometrial, ovarian, or prostate cancer and CRC risk. Population-based CRC cases and controls were recruited by the Ontario Familial Colorectal Cancer Registry (OFCCR). Logistic regression was conducted to obtain odds ratio (OR) estimates and 95% confidence intervals (95% CIs). First-degree family history of breast cancer was associated with a modest, borderline statistically significant increased CRC risk (age-, sex-adjusted OR 5 1.2, 95% CI 5 1.0, 1.5). The magnitude of CRC risk was greatest if more than one first-degree kin had breast cancer (age-, sex-adjusted OR 5 1.7, 95% CI 5 1.0, 2.0), as well as if the kin was diagnosed at >50 years of age (age-, sex-adjusted OR 5 1.4, 95% CI 5 1.1, 1.8). Family history of ovarian cancer was associated with reduced CRC risk (multivariate-adjusted OR 5 0.6, 95% CI 5 0.3, 1.0). Although statistically significant increases in CRC risk were observed in the age-, sex-adjusted OR estimates for family history of endometrial and prostate cancers, the associations were no longer significant after multivariate-adjustment. In conclusion, individuals with a first-degree kin with breast cancer may have a modest increased risk for CRC compared to individuals without. ' UICCKey words: colorectal neoplasms; cancer; family history; familial aggregation; case-control study Colorectal cancer (CRC) is the third most common type of cancer for men and women, and the second and third leading cause of cancer death for men and women, respectively, in Canada.1 The modest 5-year survival rate of CRC at 62% 1 emphasizes the importance of preventive measures such as screening and public education regarding CRC risk factors.The association between genetic factors and CRC has been well studied. However, although the association between rare, highly penetrant genetic conditions, such as familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer (HNPCC) and CRC are well-established, 2 the possible association between other hereditary factors such as common, low penetrant genes and CRC risk remains unclear.3,4 Similarly, although a family history of CRC is a known CRC risk factor, 5-12 the literature regarding CRC risk posed by a family history of other types of cancers remains inconclusive.Previous epidemiological studies have investigated the association between first-degree family history of various types of cancer and CRC risk.6,10-21 Overall, the results of these studies have varied depending on the cancer type investigated. However, statistically significant associations were reported between increased colon cancer risk and a family history of breas...

Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer

“…The response of the population-based probands approached to participate was 72% (49). MMR gene and MUTYH mutation carriers have both been associated with better colorectal cancer survival than non-carriers (50–52).…”

The genetic basis of colorectal cancer in a population-based incident cohort with a high rate of familial disease

“…Our recruitment rate of 64% is a true ascertainment rate for the population under study. Considering this is a retrospective study, all eligible cases included the deceased, and our initial contact with the patients was through their family physicians (due to Research Ethics Board requirements), this rate is quite high 32 33. Our study's recruitment rate may have increased if we recruited at the time of diagnosis or at time of surgery.…”

Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer?

“…There has been inconsistency on reporting a positive association between family history of endometrial cancer and risk of endometrial cancer [5–14], or between family history of colorectal cancer and risk of endometrial cancer [8, 11–14], or between family history of endometrial cancer and risk of colorectal cancer [6, 11, 15, 16]. All of these studies except two [12, 14] did not exclude Lynch syndrome families in which colorectal and endometrial cancers occurred in multiple family members.…”

“…All of these studies except two [12, 14] did not exclude Lynch syndrome families in which colorectal and endometrial cancers occurred in multiple family members. Further, these studies were limited as they only considered for first-degree relatives [5–13, 15, 16], or only included women aged <55 years [8, 10] or women aged 55 years and above [5, 9]. The aim of this study was to investigate whether risk of endometrial cancer for women without a MMR gene mutation depend on a family history of endometrial cancer or colorectal cancer.…”